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The fascinating science behind the first human HIV mRNA vaccine trial – what exactly does it entail?

In a moment described as a “potential first step forward” in protecting people against one of the world’s most devastating pandemics, Moderna, International AIDS Vaccine Initiative (IAVI), and the Bill and Melinda Gates Foundation have joined forces to begin a landmark trial — the first human trials of an HIV vaccine based on messenger ribonucleic acid (mRNA) technology. The collaboration between these organizations, a mixture of non-profits and a company, will bring plenty of experience and technology to the table, which is absolutely necessary when taking on this type of mammoth challenge.

The goal is more than worth it: helping the estimated 37.7 million people currently living with HIV (including 1.7 million children) and protecting those who will be exposed to the virus in the future. Sadly, around 16% of the infected population (6.1 million people) are unaware they are carriers.

Despite progress, HIV remains lethal. Disturbingly, in 2020, 680,000 people died of AIDS-related illnesses, despite inroads made in therapies to dampen the disease’s effects on the immune system. One of these, antiretroviral therapy (ART), has proven to be highly effective in preventing HIV transmission, clinical progression, and death. Still, even with the success of this lifelong therapy, the number of HIV-infected individuals continues to grow.

There is no cure for this disease. Therefore, the development of vaccines to either treat HIV or prevent the acquisition of the disease would be crucial in turning the tables on the virus.

However, it’s not so easy to make an HIV vaccine because the virus mutates very quickly, creating multiple variants within the body, which produce too many targets for one therapy to treat. Plus, this highly conserved retrovirus becomes part of the human genome a mere 72 hours after transmission, meaning that high levels of neutralizing antibodies must be present at the time of transmission to prevent infection.

Because the virus is so tricky, researchers generally consider that a therapeutic vaccine (administered after infection) is unfeasible. Instead, researchers are concentrating on a preventative or ‘prophylactic’ mRNA vaccine similar to those used by Pfizer/BioNTech and Moderna to fight COVID-19.

What is the science behind the vaccine?

The groundwork research was made possible by the discovery of broadly neutralizing HIV-1 antibodies (bnAbs) in 1990. They are the most potent human antibodies ever identified and are extremely rare, only developing in some patients with chronic HIV after years of infection.

Significantly, bnAbs can neutralize the particular viral strain infecting that patient and other variants of HIV–hence, the term ‘broad’ in broadly neutralizing antibodies. They achieve this by using unusual extensions not seen in other immune cells to penetrate the HIV envelope glycoprotein (Env). The Env is the virus’s outer shell, formed from the cell membrane of the host cell it has invaded, making it extremely difficult to destroy; still, bnAbs can target vulnerable sites on this shell to neutralize and eliminate infected cells.

Unfortunately, the antibodies do little to help chronic patients because there’s already too much virus in their systems; however, researchers theorize if an HIV-free person could produce bnABS, it might help protect them from infection.

Last year, the same organizations tested a vaccine based on this idea in extensive animal tests and a small human trial that didn’t employ mRNA technology. It showed that specific immunogens—substances that can provoke an immune response—triggered the desired antibodies in dozens of people participating in the research. “This study demonstrates proof of principle for a new vaccine concept for HIV,” said Professor William Schief, Department of Immunology and Microbiology at Scripps Research, who worked on the previous trial.

BnABS are the desired endgame with the potential HIV mRNA vaccine and the fundamental basis of its action. “The induction of bnAbs is widely considered to be a goal of HIV vaccination, and this is the first step in that process,” Moderna and the IAVI (International AIDS Vaccine Initiative) said in a statement.

So how exactly does the mRNA vaccine work?

The experimental HIV vaccine delivers coded mRNA instructions for two HIV proteins into the host’s cells: the immunogens are Env and Gag, which make up roughly 50% of the total virus particle. As a result, this triggers an immune response allowing the body to create the necessary defenses—antibodies and numerous white blood cells such as B cells and T cells—which then protect against the actual infection.

Later, the participants will also receive a booster immunogen containing Gag and Env mRNA from two other HIV strains to broaden the immune response, hopefully inducing bnABS.

Karie Youngdahl, a spokesperson for IAVI, clarified that the main aim of the vaccines is to stimulate “B cells that have the potential to produce bnAbs.” These then target the virus’s envelope—its outermost layer that protects its genetic material—to keep it from entering cells and infecting them.  

Pulling back, the team is adamant that the trial is still in the very early stages, with the volunteers possibly needing an unknown number of boosters.

“Further immunogens will be needed to guide the immune system on this path, but this prime-boost combination could be the first key element of an eventual HIV immunization regimen,” said Professor David Diemert, clinical director at George Washington University and a lead investigator in the trials.

What will happen in the Moderna HIV vaccine trial?

The Phase 1 trial consists of 56 healthy adults who are HIV negative to evaluate the safety and efficacy of vaccine candidates mRNA-1644 and mRNA-1644v2-Core. Moderna will explore how to deliver their proprietary EOD-GT8 60mer immunogen with mRNA technology and investigate how to use it to direct B cells to make proteins that elicit bnABS with the expert aid of non-profit organizations. But readers should note that only one in every 300,000 B cells in the human body produces them to give an idea of the fragility of the probability involved here.

Sensibly, the trial isn’t ‘blind,’ which means everyone who receives the vaccine will know what they’re getting at this early stage. That’s because the scientists aren’t trying to work out how well the vaccine works in this first phase lasting approximately ten months – they want to make sure it’s safe and capable of mounting the desired immune response.

And even though there is much hype around this trial, experts caution that “Moderna are testing a complicated concept which starts the immune response against HIV,” says Robin Shattock, an immunologist at Imperial College London, to the Independent. “It gets you to first base, but it’s not a home run. Essentially, we recognize that you need a series of vaccines to induce a response that gives you the breadth needed to neutralize HIV. The mRNA technology may be key to solving the HIV vaccine issue, but it’s going to be a multi-year process.”

And after this long period, if the vaccine is found to be safe and shows signs of producing an immune response, it will progress to more extensive real-world studies and a possible solution to a virus that is still decimating whole communities.

Still, this hybrid collaboration offers future hope regarding the prioritization of humans over financial gain in clinical trials – the proof is that most HIV patients are citizens of the third world.

As IAVI president Mark Feinberg wrote in June at the 40th anniversary of the HIV epidemic: “The only real hope we have of ending the HIV/AIDS pandemic is through the deployment of an effective HIV vaccine, one that is achieved through the work of partners, advocates, and community members joining hands to do together what no one individual or group can do on its own.”

Whatever the outcome, money is no longer a prerogative here, and with luck, we may see more trials based on this premise very soon.

Immune cells from the common cold offer protection against COVID-19, researchers find

If one in 10 cold infections are from coronaviruses, then antibodies produced from these illnesses could surely give a bit more protection against COVID-19, right? A new study has just provided the answer to this question by showing that immunity induced by colds can indeed help fight off the far more dangerous novel coronavirus.

Image credits: Engin Akyurt.

A study from Imperial College London that studied people exposed to SARS-CoV-2 or COVID-19 found that only half of the participants were infected, while the others tested negative. Before this, researchers took blood samples from all volunteers within days of exposure to determine the levels of an immune cell known as a T cell – cells programmed by previous infections to attack specific invaders.

Results show that participants who didn’t test positive had significantly higher levels of these cells; in other words, those who evaded infection had higher levels of T cells that attack the Covid virus internally to provide immunity — T cells that may have come from previous coronavirus infections (not SARS-CoV-2). These findings, published in the journal Nature Communications, may pave the way for a new type of vaccine to prevent infection from emerging variants, including Omicron.

Dr. Rhia Kundu, the first author of the paper from Imperial’s National Heart & Lung Institute, says: “Being exposed to the SARS-CoV-2 virus doesn’t always result in infection, and we’ve been keen to understand why. We found that high levels of pre-existing T cells, created by the body when infected with other human coronaviruses like the common cold, can protect against COVID-19 infection.” Despite this promising data, she warns: “While this is an important discovery, it is only one form of protection, and I would stress that no one should rely on this alone. Instead, the best way to protect yourself against COVID-19 is to be fully vaccinated, including getting your booster dose.”

The common cold’s role in protecting you against Covid

The study followed 52 unvaccinated people living with someone who had a laboratory-confirmed case of COVID-19. Participants were tested seven days after being exposed to see if they had caught the disease from their housemates and to analyze their levels of pre-existing T cells. Tests indicated that the 26 people who tested negative for COVID-19 had significantly higher common cold T cells levels than the remainder of the people who tested positive. Remarkably, these cells targeted internal proteins within the SARS-CoV-2 virus, rather than the spike protein on its surface, providing ‘cross-reactive’ immunity between a cold and COVID-19.

Professor Ajit Lalvani, senior author of the study and Director of the NIHR Respiratory Infections Health Protection Research Unit at Imperial, explained:

“Our study provides the clearest evidence to date that T cells induced by common cold coronaviruses play a protective role against SARS-CoV-2 infection. These T cells provide protection by attacking proteins within the virus, rather than the spike protein on its surface.”

However, experts not involved in the study caution against presuming anyone who has previously had a cold caused by a coronavirus will not catch the novel coronavirus. They add that although the study provides valuable data regarding how the immune system fights this virus, it’s unlikely this type of illness has never infected any of the 150,000 people who’ve died of SARS-CoV-2 in the UK to date.

Other studies uncovering a similar link have also warned cross-reactive protection gained from colds only lasts a short period.

The road to longer-lasting vaccines

Current SARS-CoV-2 vaccines work by recognizing the spike protein on the virus’s outer shell: this, in turn, causes an immune reaction that stops it from attaching to cells and infecting them. However, this response wanes over time as the virus continues to mutate. Luckily, the jabs also trigger T cell immunity which lasts much longer, preventing the infection from worsening or hospitalization and death. But this immunity is also based on blocking the spike protein – therefore, it would be advantageous to have a vaccine that could attack other parts of the COVID virus.

Professor Lalvani surmises, “The spike protein is under intense immune pressure from vaccine-induced antibodies which drives the evolution of vaccine escape mutants. In contrast, the internal proteins targeted by the protective T cells we identified mutate much less. Consequently, they are highly conserved between the SARS-CoV-2 variants, including Omicron.” He ends, “New vaccines that include these conserved, internal proteins would therefore induce broadly protective T cell responses that should protect against current and future SARS-CoV-2 variants.”

Discovery of a new target promises a long-lasting, universal flu vaccine

An international research effort might finally lead us to a universal, long-lasting flu vaccine.

Image via Pixabay.

Influenza, or ‘the flu’, is one of the most persistent viruses that humanity has contended with throughout history. Although several vaccines against the flu have been developed and deployed year after year, the virus’ high rate of mutation means that it often bypasses our bodies’ immunity. It also leads to a huge number of influenza strains, often quite different from one another, making it hard for a single vaccine to provide immunity against all of them at the same time.

So far, we’ve been unable to develop a single, long-lasting, and broadly-acting vaccine against the flu. However, new research might change this.

Targeting the anchor

“It’s always very exciting to discover a new site of vulnerability on a virus because it paves the way for rational vaccine design,” says co-senior author Andrew Ward, PhD, professor of Integrative Structural and Computational Biology at Scripps Research. “It also demonstrates that despite all the years and effort of influenza vaccine research there are still new things to discover.”

The findings come from a combined effort of researchers at Scripps Research, University of Chicago and Icahn School of Medicine at Mount Sinai. Their work revealed a previously-unknown vulnerability of the influenza virus — a section that is very stable across time and strains (i.e. it doesn’t mutate almost at all) which the team dubs ‘the HA anchor’.

Since this anchor is common among strains and doesn’t change over time, a vaccine designed to interact with this anchor will be effective across strains and over the years, despite the virus’ propensity to mutate.

“By identifying sites of vulnerability to antibodies that are shared by large numbers of variant influenza strains we can design vaccines that are less affected by viral mutations,” says study co-senior author Patrick Wilson, MD. “The anchor antibodies we describe bind to such a site. The antibodies themselves can also be developed as drugs with broad therapeutic applications.”

On average, influenza infects over 20 million people and leads to 20,000 deaths in the United States alone — many more worldwide. Current vaccines target an area on the virus known as the head of hemagglutinin (HA), a protein that extends outwards from its shell. Although this area is easy to reach and highly reactive, which makes it a good target for our immune system, it’s also one of the most volatile parts of the virus, changing very rapidly. It’s the mutations of the HA that make it necessary for new influenza vaccines to be developed every year.

For the study, the team looked at 358 flu antibodies from the blood of people who had been either vaccinated with a seasonal influenza vaccine, universal influenza vaccine, or had been infected with the virus.

Many of the antibodies they analyzed were already known to science and targeted known areas of the virus. However, a few stood out — they had not previously been documented and tied to a new area. This led the team to discover the anchor. In total, 50 different antibodies from 21 individuals were identified tying to this area. Mouse studies in the lab showed that these antibodies were effective against three H1 influenza viruses.

“In order to increase our protection against these highly mutating viruses, we need to have as many tools as we can,” says Julianna Han, a staff scientist in the Ward lab and one of the paper’s co-first authors. “This discovery adds one more highly potent target to our repertoire.”

“The human immune system already has the ability to make antibodies to this epitope, so it’s just a matter of applying modern protein engineering methods to make a vaccine that can induce those antibodies in sufficient numbers,” adds Jenna Guthmiller, a postdoctoral fellow at the University of Chicago, the other co-first author.

The team is now working to design a vaccine that better targets the HA anchor of the virus.

The paper “Broadly neutralizing antibodies target a hemagglutinin anchor epitope” has been published in the journal Nature.

Not only is mixing COVID-19 vaccines safe — it provides better protection than a single type

A study into COVID-19 vaccines found that people have higher levels of immunity when receiving the first dose of AstraZeneca or Pfizer followed by a Moderna or Novavax shot nine weeks after, compared to two shots of the same vaccine. While this is a relatively small study, it seems to suggest that the mix-and-match approach works when it comes to COVID-19 vaccines — at least in some combinations.

Image credit: Flickr / Province of British Columbia.

Researchers at the University of Oxford tested vaccine combinations on a group of over 1,000 volunteers over 50. The Moderna and Novavax vaccines increased immunity after the AstraZeneca vaccine, compared to a second AstraZeneca shot, while only Moderna increased antibodies after Pfizer, compared to a full vaccination with Pfizer. 

Mix and match

The COVID-19 pandemic has already caused more than five million deaths to date — and with new variants constantly emerging, there’s no way out of the pandemic other than vaccination.

Over three billion people were vaccinated with at least one dose, but that figure is only 2% to 8% in low-income countries. Around the world, 24 Covid-19 vaccines have been already approved, but manufacturing and distribution remain major challenges, especially in the less-developed parts of the world. For countries like this, where availability is a problem, mixing between different vaccines could be a game-changer, the researchers suggest.

Results varied based on the particular type of vaccine mix. The researchers found levels of antibodies 17 times higher in those individuals who got the first shot of AstraZeneca followed by a shot of Moderna, and four times higher when followed by Novavax. Meanwhile, for those who got the first jab of Pfizer, antibodies were 1.3 times higher when getting a second shot of Moderna and 20% lower with Novavax. 

The team at Oxford also explored the impact of vaccine combinations against novel COVID-19 variants, specifically the Delta and the Beta ones. In both cases, they registered a reduction in the levels of antibodies and a very little drop in T-cell responses. The Omicron variant, which was just recently discovered, wasn’t included in the study. 

Of the mixed schedules studied, perhaps the most relevant to low-income countries is the AstraZeneca/Novavax, the researchers argued, as neither require ultra-low temperature storage and also given the low cost of the AstraZeneca. The WHO is expected to soon authorize the Novavax to be delivered through the Covax initiative.   

Validating a strategy

While previous studies demonstrated the short-term safety of vaccine combinations, this is the first one to publish data from randomized controlled trials examining the immunity levels and safety of using different vaccines over a longer period of time. 

“Multiple vaccines are appropriate to complete primary immunisation following priming with BNT (Pfizer) or ChAd (AstraZeneca), facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification,” the researchers, members of the Oxford Vaccine’s Group Com-Cov, wrote in The Lancet. 

Several countries had already been using vaccine combinations for a while now, especially as they were faced with low vaccine supplies and slow vaccination campaigns. This was the case of Germany, for example, which offered booster shots of Pfizer and Moderna to vulnerable individuals, regardless of their previous vaccine. But not everyone supports this strategy.

Back in July, the World Health Organization advised people against mixing and matching COVID-19 vaccines, and it remains to be seen whether this recommendation will change in light of the new information. Mixing vaccines could offer new hope to lower-income countries that have not completed their primary vaccination campaigns and could now start using different vaccine brands. 

The study was published in the journal The Lancet.

New vaccine kills HIV in monkeys. Could it work in humans?

It’s still early days, but researchers are hopeful that a new approach could pave the way for a working HIV vaccine in humans that could save millions of lives.

Credits: Mufid Majnun.

We’ve heard a lot about vaccines in the ongoing pandemic, and we’ve seen important breakthroughs in a relatively short amount of time, and this renewed interest in vaccines doesn’t only apply to COVID-19. A new study carried out in Japan reported a new vaccine that kills HIV in crab-eating macaques, a type of test monkey often used for medical tests.

The vaccine uses an adjuvant — an ingredient that helps to create a stronger immune response. Adjuvants help the body produce an immune response strong enough to protect the person from the disease. Adjuvants have been used before in some vaccines; for instance, the anthrax, chickenpox, and some influenza vaccines use an adjuvant.

In this case, the researchers focused on a bacterium that secretes a substance that strengthens the immune response. They administered the vaccine to the macaques and observed that it protected all of them against HIV, up to the point where tests couldn’t find any traces of the HIV vaccine. The vaccinated macaques were then given a stronger virus that always kills the victim, but the virus disappeared in 6 out of the 7 subjects.

Blood and lymph nodes were extracted from the surviving macaques and injected into healthy monkeys and also provided immunity.

The results are promising, but getting a vaccine to work on monkeys is one thing, and getting it to work on humans is another. Researchers are working on developing clinical testing on humans, but this won’t happen overnight — the plan is to have results within five years, researchers say..

Although HIV incidence has declined in recent years, it remains a major problem, especially in some regions of Africa. It’s estimated that HIV kills around 1 million people every year and it still remains a global healthcare crisis. Since 1981, HIV has killed over 35 million people.

While treatments for HIV do exist, and especially when applied early, they can keep the virus in check, they don’t actually destroy the virus — and treatment can be quite expensive.

Having access to a vaccine (especially a cheap vaccine that could be deployed cost-effectively) could be a game-changer and put a big dent in the worldwide HIV outbreak. This isn’t the first attempt of developing an HIV vaccine — far from it. Earlier this year, a Phase I trial showed promise, but several HIV vaccines have reached Phase III, only to show insufficient results. Several notable trials are currently underway.

HIV has proven to be a resilient and adaptable virus, which is why it’s so important to develop a working vaccine against it as quickly as possible. Whether or not this new approach will work in humans remains to be seen.

A vaccine cuts the risk of cervical cancer by 90%

A vaccine for cancer almost sounds too good to be true, but in the case of cervical cancer, it’s happening already. A new study in the UK shows that the human papillomavirus (or HPV) vaccine is already cutting cases of cervical cancer by up to 90%.

Image credits: Flickr/Ted Eytan.

Vaccinating against cancer

There are many different types of cancer, and they often manifest themselves in different ways. Increasingly, research is showing that some types of cancers are caused by viruses — and as dreadful as that sounds, it opens up an opportunity: if we can prevent the viruses from doing damage, we could also prevent those cancers from developing.

This is exactly what’s happening with HPV. HPV infections typically cause no symptoms and 90% of them resolve naturally within two years. However, in some cases, the infection can result in either warts or lesions. These lesions can increase the risk of cancer — not just in the cervix, but also in the anus, vagina, throat, penis, or tonsils.

Thankfully, there’s a vaccine for HPV. HPV vaccines are very safe and have been shown to be extremely effective against cervical cancer (as well as other types of cancer) in trials. As a result, several countries have started vaccination campaigns, especially focusing on teenage girls. In England, a vaccination program was launched 13 years ago, and now, evidence shows that cervical cancer rates in women offered the vaccine between the ages of 12 and 13 (now in their 20s) were 87% lower than in the unvaccinated population. Cases in this age group (which are relatively rare) just dropped from 50 a year to around 5 a year.

The HPV vaccine can only prevent an infection — it can’t do anything if you’re already infected with the virus. This is a key problem because the virus is so widespread that immunization campaigns have to be aimed at children before they are sexually active (as the virus is transmitted through sexual contact).

In the UK, girls are offered the vaccine between the ages of 11 and 13, and since 2019, the vaccine has also been offered to boys. Although the virus is not as harmful to boys, it can still raise the risk of some cancers, and boys can also be carriers and pass the virus on.

The power of science

The investigated vaccine (Cervarix) was administered in England from 2008 to 2012. A different one (Gardasil), which offers protection for more HPV variants, is administered now. The study, which has been published in The Lancet, found a 97% drop in pre-cancerous changes in women vaccinated between the ages of 12 and 13, 75% in women vaccinated between the ages of 14 and 16, and 39% in women vaccinated between the ages of 16 and 18.

“The HPV immunisation programme has successfully almost eliminated cervical cancer in women born since Sept 1, 1995,” the study reads.

Overall, researchers estimate that the vaccine prevented 17,200 cervical carcinomas (pre-cancers) in England. The results were even better than expected. Cancer Research UK chief executive Michelle Mitchell said the results are a triumph of science and an important milestone in our fight against cancer:

“Results like this show the power of science. It’s a historic moment to see the first study showing that the HPV vaccine has and will continue to protect thousands of women from developing cervical cancer.”

Almost 9 in 10 severe cases of cervical cancer occur in low and middle-income countries, where there is little access to cervical cancer screening. This is why researchers believe that a vaccination campaign in these countries would make a much bigger impact than in wealthier nations such as the UK. Supported by the World Health Organization (WHO), over 100 countries have now implemented similar campaigns, and the WHO believes that with this type of campaign, we can actually eliminate cervical cancer across the world. Although that’s still a ways away now, the fact that we can vaccinate against a type of cancer is fantastic news.

Cervical cancer is the fourth most common type of cancer in women in the world, killing more than 300,000 each year.

India has administered 1 billion vaccine doses to its citizens, moving closer to 100% goal

Last week, India passed an important milestone: the country has administered 1 billion doses of COVID vaccine to its citizens, according to government data. With this, roughly 75% of its population has been immunized with at least one dose — around 708 million people. Around one-third (30%) of the country has been fully immunized with two shots of vaccine.

Image credits Christian Emmer.

Other countries have managed similar vaccination rates as percentages of their population — Canada, for example, sits at around the 77% mark, while Portugal hit 88% — but India’s achievement impresses through sheer numbers. One billion doses are no small feat.

The country has had a pretty rough experience with this pandemic. But it also made sizeable efforts to contend with the virus, and this achievement carries on that trend.

For example, India was among the first countries to issue lockdowns and use contact tracing to limit the spread of the coronavirus. Still, things have not been going swimmingly for the country, especially since the rise of the Delta variant, and for a long time, India was among the countries with the most cases.

High score

“This achievement belongs to India, every citizen of India,” wrote Indian Prime Minister Narendra Modi on Twitter (original tweet in Hindi). “I express my gratitude to all the vaccine manufacturing companies of the country, workers engaged in vaccine transportation, health sector professionals engaged in vaccine development.”

India’s very large population, currently inching toward the 1.4 billion mark, is one of the factors working against its efforts to combat the coronavirus pandemic. Other populous countries know how challenging it can be to source, deliver, and administer a large number of vaccine doses. Even countries with lower populations but robust infrastructures and strong economies — like the USA — have had their own hiccups in vaccination efforts.

Apart from this, India’s population is still largely rural, living outside metropolitan areas. Its economy, although large and diverse, is still mostly people-driven, and much less resilient to public health issues than those of more developed countries. Its infrastructure is also relatively undeveloped in many geographical areas.

This all makes the country’s vaccination milestone all that much more impressive.

Against this backdrop, New Delhi is setting even more ambitious goals for itself. Government officials are aiming to have all of India’s adult population vaccinated by the end of the year. I, personally, cheer them on, although I do have my reservations regarding how feasible such a target actually is. Experience in other areas of the world shows us that the last steps towards full vaccination are the hardest, and slowest to go through.

Still, reaching that goal means India will need to administer around 1.8 billion doses. A production target the government set in June called for 2 billion doses to be produced by December. Local manufacturers have reportedly ramped up production in recent months to reach that target.

India started its vaccination program in January of this year. So far, only those above 18 years of age can receive a shot. Several vaccines have been approved for use by the government, including the AstraZeneca shot and the Russian Sputnik-V. A new vaccine, a three-dose shot produced by local manufacturer Cadila Healthcare, has also been approved for use in those under 18.

There are over 70,000 state-run vaccination centers currently administering free shots in India. A further 2,000 private centers also offer vaccine shots, although these charge for the service.

Eight months later: researchers quantify the long-term effectiveness of COVID-19 vaccines

As many of us are nearing the one-year mark following our immunization, questions still remain regarding the long-term efficacy of our current vaccines. New research, however, is looking into it.

Image via Pixabay.

A team of researchers from the Beth Israel Deaconess Medical Center (BIDMC) has been analyzing the long-term immunization efficacy of the three vaccines approved by the U.S. Food & Drug Administration in December 2020. These are BNT162b2 (BioNTech, Pfizer), mRNA-1273 (Moderna), Ad26.COV2.S (Johnson & Johnson).

They evaluated the immune response produced by these vaccines at two to four weeks after complete immunization (i.e. after receiving the full number of shots) to that at eight months after vaccination.

Declining but not determined

“The mRNA vaccines were characterized by high peak antibody responses that declined sharply by month six and declined further by month eight,” said corresponding author Dan H. Barouch, MD, Ph.D., director of the Center for Virology and Vaccine Research at BIDMC, who helped develop the Ad26 platform in collaboration with Johnson & Johnson.

“The single-shot Ad26 vaccine induced lower initial antibody responses, but these responses were generally stable over time with minimal to no evidence of decline.”

Understanding the long-term efficacy of these vaccines is critical for our efforts to combat the COVID-19 pandemic. However, we didn’t have such information on hand up to now. Simply put, while the vaccines were tested to ensure safety and efficacy, the global context meant that their development process was greatly accelerated. We simply didn’t have the opportunity to obtain data pertaining to their long-term efficacy.

In a bid to help patch up this hole in our understanding, the team at BIDMC monitored the immunization levels of 61 participants over an eight-month period after they received their vaccines. The team measured the levels of antibodies, T cells, and other immune markers in the blood of these participants at two to four weeks after they received their shot (which is the point of peak immunity) and monitored them over an eight-month follow-up period.

Out of the 61 total participants involved, 31 received the BioNTech / Pfizer vaccine, 22 received the Moderna one, with the final 8 receiving the Johnson & Johnson single-shot vaccine.

All in all, the team explains that the Moderna vaccine produced more powerful and longer-lasting immunization effects than the BioNTech / Pfizer variant. That being said, all three variants produced effective immune responses against SARS-CoV-2 and had broad cross-reactivity to its strains.

However: the authors report that both mRNA-based vaccines (BioNTech / Pfizer and Moderna) produced sizable initial immune responses, but these got progressively weaker over time. At around the 6-month mark, immune markers in patients who received either of these two had already declined sharply compared to the 2-to-4 week mark. The same markers would decline even further at the eight-month mark.

The single-shot Johnson & Johnson vaccine, meanwhile, produced a weaker initial effect but was much more consistent over the study period.

Although these results might not sound very exciting or promising, they do not mean that the vaccines leave us vulnerable over time. For starters, there are still a lot of unknowns regarding exactly what immune responses in our bodies are needed to protect against SARS-CoV-2.

Furthermore, what the team tracked here are physical markers of immunity. But the antibodies themselves, for example, are the ‘soldiers’ that our body uses to protect itself against viruses. Their presence in the bloodstream is akin to our body being on alert. But even if they are not physically there, our bodies have already been primed regarding the structure of the virus, how to identify it, and which antibodies are needed to defeat it. Against this backdrop, an immune response against the pathogen can be mounted very quickly in case of infection.

“Even though neutralizing antibody levels decline, stable T cell responses and non-neutralizing antibody functions at 8 months may explain how the vaccines continue to provide robust protection against severe COVID-19,” said lead author Ai-ris Y. Collier, MD, a maternal-fetal medicine specialist at BIDMC.

“Getting vaccinated (even during pregnancy) is still the best tool we have to end the COVID-19 pandemic.”

The paper “Differential Kinetics of Immune Responses Elicited by Covid-19 Vaccines” has been published in the New England Journal of Medicine.

The first malaria vaccine is finally here: WHO endorsement received

Credit: Flickr, Pixabay.

Scientists have been working on a vaccine against malaria — an infectious disease spread by mosquitoes that infects over 230 million people annually and kills 400,000, most of whom are children — since the 1980s. More than thirty years in the making, the first malaria vaccine has finally passed its Phase III clinical trials in three African countries and the World Health Organization (WHO) now recommends its approval.

A lifesaver for children worldwide

The vaccine, known as RTS,S (trade name Mosquirix), was developed by GlaxoSmithKline. It started its first pilot immunization program in Ghana, Kenya, and Malawi where it was found to prevent approximately 4 in 10 malaria cases, including 3 in 10 cases of life-threatening severe malaria. Furthermore, the vaccine also cut the level of severe anemia—the most common reason kids die from the disease—by 60%.

The Mosquirix vaccine is given in three doses between the ages of 5 months and 17 months, with a fourth dose about 18 months later. The most recently closed clinical trials have shown Mosquirix is 50% effective against severe malaria in the first year. However, the vaccine-granted immunity wanes with time, its efficacy plummeting close to zero by the fourth year.

After these clinical trials, the vaccine coverage was expanded to include more than 800,000 children who have received 2.3 million doses of the vaccine thus far. This program showed that the vaccine was 40% effective in the ‘real world’.

If the vaccine was rolled out extensively in countries with the highest incidence of malaria, 5.4 million cases and 23,000 deaths among children younger than 5 years could be prevented annually, according to a modeling study from 2020.

According to Kate O’Brien, the Director of WHO’s Department of Immunization, Vaccines, and Biologicals, young infants are at the highest risk of severe outcomes, and so having a vaccine that can prevent disease in children and infants would be a groundbreaking new strategy.

“This is a historic moment. The long-awaited malaria vaccine for children is a breakthrough for science, child health and malaria control,” said WHO Director-General Dr. Tedros Adhanom Ghebreyesus in a statement. “Using this vaccine on top of existing tools to prevent malaria could save tens of thousands of young lives each year.”

Malaria: a hard nut to crack

Although tremendous advances have been made against malaria over the last two decades thanks to prevention and control measures, such as insecticide-treated bed nets, indoor spraying with insecticides, and the timely use of malaria testing and treatment, progress has stalled or even reversed in some areas. The long-awaited vaccine was the missing puzzle piece that health workers were looking for in their long war against malaria.

Malaria is transmitted through the bite of a mosquito that was infected with the Plasmodium parasite. Symptoms include fever, chills, headache, anemia, convulsions, and sweating. A single bite from a malaria-infected mosquito will cause several bouts of the disease, which means a lot of missed school and progressively poorer health during formative years.

There are over 100 different malaria-causing parasites, but Mosquirix only targets one, which is the most common and deadly in Africa: Plasmodium falciparum.

While the COVID mRNA vaccines were designed in a matter of days and immediately started clinical trials, the malaria vaccine took decades to mature. The huge discrepancy is owed to the malaria parasite’s much more sophisticated nature than the coronavirus. Plasmodium parasites have evolved to evade our immune system, being able to hide in the host’s liver and emerge many times over a period of years. To gain natural immunity, you have to be infected multiple times with the parasite. During some of these infections, you risk death. You could say we’ve been lucky that the pandemic is a coronavirus one and not a Plasmodium one.

“From a scientific perspective, this is a massive breakthrough, from a public health perspective this is a historical feat,” said Dr. Pedro Alonso, the director of the WHO Global Malaria Programme.

“We’ve been looking for a malaria vaccine for over 100 years now, it will save lives and prevent disease in African children.”

Malaria vaccines could prove even better in the future. The Jenner Institute at the University of Oxford developed a vaccine against malaria that was shown to be 77% effective in trials in Africa, earlier this year. 

Vaccine-coated, 3D-printed patches may soon replace a syringe near you

Do you hate needles, but still want to get vaccinated? Researchers at Stanford University and the University of North Carolina at Chapel Hill have got your back. They developed a new, 3D-printed patch that can get you immunized without any jab.

Design and environmental scanning electron microscope (ESEM) images of the microneedles. (E) is a fluorescence image of the patch in (D). Image credits Cassie Caudill et al., (2021), PNAS.

The patch works even better than a traditional vaccine, its designers explain, as it delivers the compound directly into the skin — which is full of immune cells that respond to it. The resulting immune response is around 10 times greater than that produced by injection through a needle into muscle tissue. However, these findings, for now, should be taken with a pinch of salt; they were obtained from a study conducted with animals, not humans.

Performance patch

“In developing this technology, we hope to set the foundation for even more rapid global development of vaccines, at lower doses, in a pain- and anxiety-free manner,” said lead study author and 3D printing entrepreneur Joseph M. DeSimone, professor of translational medicine and chemical engineering at Stanford University and professor emeritus at UNC-Chapel Hill.

To be fair, it isn’t the patch itself that does the job, but rows upon rows of microneedles coated in vaccine on its underside. These are lined up and, individually, they’re barely long enough to reach the skin, where they dissolve, releasing the vaccine.

One of the main selling points of this technology, in the eyes of the authors, is the ease of use and transportability. For patients, it’s likely that the painlessness of this over other delivery methods will be its most attractive trait, as will the fact that they can administer the patches to themselves without any type of risk.

Application of this patch led to a significant antibody response in lab animals. According to the team, this response was 50 times greater than what would be produced by a direct injection under the skin. This increased response could lead to dose sparing — essentially, immunizing a larger crowd of people on the same quantity of vaccine — as each patch uses a smaller dose to produce the same response as delivery via syringe.

The concept of microneedles has been of interest to the scientific community for quite some time now, but they never really caught on due to difficulties in customizing them for different vaccines. Although 3D printing has given the authors a way to break through past limitations, it’s generally a challenge to adapt microneedles to different vaccine types:

“These issues, coupled with manufacturing challenges, have arguably held back the field of microneedles for vaccine delivery,” said lead study author Shaomin Tian, a researcher in the Department of Microbiology and Immunology in the UNC School of Medicine. “Our approach allows us to directly 3D print the microneedles which gives us lots of design latitude for making the best microneedles from a performance and cost point-of-view.”

Instead of relying on the traditional approach of creating a mold and then casting the microneedles, the team prints each one out individually. This was carried out at the University of North Carolina at Chapel Hill using a CLIP prototype 3D printer that DeSimone invented and is produced by CARBON, a Silicon Valley company he co-founded.

Although the quick development of a vaccine remains a key aspect of fighting against a pandemic, our experiences this last year have shown that logistical factors remain an important component limiting our ability to react. This process seems simple — go to a hospital, have someone retrieve a vaccine from a freezer, draw it into a syringe, and administer the shot — but it still poses quite some hurdles from a mass-vaccination standpoint.

For starters, such an approach simply cannot work in areas that lack cold storage, or where there aren’t enough trained professionals to perform the vaccinations. Getting a shot this way also involves going to a hospital or clinic, something not everybody is able or willing to do.

These patches, the team explains, can be delivered anywhere in the world without any special requirements for storage or transportation. They can be applied easily and safely at home without the presence of any trained individuals. This, by itself, could also help boost vaccination rates, the team adds.

“One of the biggest lessons we’ve learned during the pandemic is that innovation in science and technology can make or break a global response,” DeSimone said. “Thankfully we have biotech and health care workers pushing the envelope for us all.”

The paper “Transdermal vaccination via 3D-printed microneedles induces potent humoral and cellular immunity” has been published in the journal PNAS.

Antibodies against the first coronavirus strain aren’t very effective against emerging forms of the virus

Antibodies from the original strain of the virus that causes COVID-19, the one which started this pandemic, likely do not bind well to newer strains. The findings raise new concerns regarding emerging variants of the virus.

Image credits Katja Fuhlert.

Research from the University of Illinois Urbana-Champaign reports that antibodies against the original coronavirus strain aren’t that effective against some of the strains which developed later. The metastudy analyzed published studies to obtain patient data related to the sequence of antibodies they produced in response to the virus. These antibodies work by binding to, and thus neutralizing, the molecule that allows this virus to infect our cells — a particular spike protein on its surface.

While the antibodies recorded so far in patients who fought off the infection worked well against the original coronavirus strain, they’re not that effective in binding to emerging strains, the team explains. Understanding what kind of antibodies we naturally produce against a particular infection is a key step in the development of a vaccine, they add, so the results of this study could go a long way towards nipping a new pandemic in the bud.

Old dog, new tricks

“Antibody response is quite relevant to everything from understanding natural infection and how we recover from infection to vaccine design. The body has the capability to produce diverse antibody responses—it’s estimated we could make a trillion different antibodies. So when you see people are making quite similar antibodies to a particular virus, we call it convergent antibody response,” says Nicholas Wu, a professor of biochemistry at the University of Illinois, and lead author of the paper.

“That means we can design vaccines trying to elicit this kind of antibody response, and that is probably going to improve the responsiveness of more individuals to the vaccine.”

The team reports that the antibody response to the original virus was consistent among patients. Two main groups of antibodies were identified from published literature on this topic, and both bound well to the virus’ spike protein. Both were, also, quite effective in neutralizing the virus by targeting this protein. As such, our vaccines were also tailored to teach our bodies how to identify and attack the spike protein.

But the data gathered by the authors show that neither of these two groups of antibodies worked particularly well against newer variants of the virus. This has some pretty unpleasant implications for our current vaccines. As they are designed to coax our bodies into producing antibodies that attack the spike protein present on the original coronavirus, and these antibodies don’t bind very well to new strains, we have cause to question how effective current vaccines are at stopping new strains. At the same time, the results point to a particular weakness in our defense, one we could, potentially, fix through the use of vaccine boosters or a similar approach. In epidemiology, “what I don’t know can’t hurt me” is an approach that will get you killed.

“We really focused on characterizing the antibodies created in those infected with the original strain of the virus,” says graduate student Timothy Tan, the first author of the study. “Before we started the study, variants weren’t much of a problem. As they emerged, we wanted to see whether the common antibodies we identified were able to bind to newer variants.”

“Even though this antibody response is very common with the original strain, it doesn’t really interact with variants,” Wu said. “That, of course, raises the concern of the virus evolving to escape the body’s main antibody response. Some antibodies should still be effective—the body makes antibodies to many parts of the virus, not only the spike protein—but the particular groups of antibodies that we saw in this study will not be as effective.”

The team plans to extend their research to the antibody responses to the delta variant and other strains of the coronavirus. Their main objective is to see whether these strains also produce a convergent response in patients, and how the antibodies for these differ from the original strain

“We want to design vaccines and boosters, if needed, that can protect a majority of the population,” Tan said. “We expect that the antibody response to those variants would be quite different. When we have more data about the antibodies of patients who have been infected with variants, understanding the difference in the immune response is one of the directions that we would like to pursue.”

The paper “Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain” has been published in the journal Nature Communications.

At my hospital, over 95% of COVID-19 patients share one thing in common: They’re unvaccinated

gray gatch bed in hospital

As an emergency medicine and critical care doctor at the University of Washington School of Medicine in Seattle, I’ve lost count of the number of COVID-19 surges since the U.S. pandemic began in Seattle in February 2020. But this one feels different. The patients are younger. They have fewer preexisting medical conditions. And at my hospital, over 95% of these hospitalized patients share one common feature: They’re unvaccinated.

While I’m grateful to see news of the FDA’s recent full approval of one of the COVID-19 mRNA vaccines, the science has been clear in my mind for quite some time. mRNA vaccines, first developed over nearly 50 years, are nothing short of a miracle of science designed for situations just like a respiratory virus pandemic. The vaccines are the most effective tool we have to prevent severe illness and hospitalization and protect our precious health care resources. Some of my colleagues just published a study showing exactly this.

Of course, every medical treatment has risks and potential side effects, but we’ve witnessed the world’s largest vaccine trial, with more than 200 million people in the U.S. receiving at least one dose. Doctors can confidently say that vaccine side effects are rare and generally mild, and rumors about vaccines altering DNA or causing infertility are completely unfounded, with no scientific basis.

But I also have sympathy for those who fell victim to disinformation. Too many times I’ve been asked by a family member of a dying patient with COVID-19 if it was too late for the vaccine. Too many times, I’ve had to say yes. The next question is often, “Is there anything else that can be done?” Too often, the answer is no.

Having this conversation over and over again, often over teleconferencing software or the phone, is exhausting and profoundly sad, especially knowing that, in the case of unvaccinated patients, it likely could have been prevented.

I realize that not everybody sees what I see every day. While stories about vaccine reactions abound, few hear about the realities of severe COVID-19 infection. However, when I close my eyes at night, I see the healthy 27-year-old man who died after four weeks hooked up to machines that tried to keep him alive, and the young family he left behind. I see the 41-year-old woman now weak and permanently disabled after a long hospital stay. I see the 53-year-old farmworker who now requires dialysis after developing renal failure, a common complication of severe COVID-19. And countless more.

I often hear claims of “99% survival” from COVID-19 with or without the vaccine, but in reality, the facts are much more staggering. Nearly 1 in 500 Americans has died from this disease, and for those who survive, the devastation is like nothing I’ve ever seen. Holes in lungs, muscle wasted, organs failing one by one – millions of people will suffer physical, psychological and financial consequences that will last months or years, a toll difficult to quantify.

The impact on our health care system is also difficult to quantify. Staffing, even more than beds or ventilators, is critically low. In Washington state, Texas and across the country, experienced health care workers are leaving the profession in droves, exasperated by the continuous onslaught of sick COVID-19 patients and a demanding work environment. People – nurses, respiratory therapists, doctors, physical therapists, sanitation workers – do the work in hospitals; a hospital bed is worthless without staff to provide care.

Because of these staffing shortages, hospitals are closing, and the inequities and weaknesses in an already-stretched health care system are being exposed. Revered as “health care heroes” just a year ago, doctors are being heckled and even assaulted after speaking out about science at school board meetings.

I’m frustrated that more Americans have not chosen to get vaccinated, to wear masks, to take this pandemic seriously. I often wonder what 2021 would look like if they had. For example, we’ve worn masks in the hospital for years for procedures and to protect us from other respiratory viruses. We know that the SARS-CoV-2 virus can be spread by aerosols that remain suspended in the air, and that some masks can’t entirely block these droplets. But we also know that COVID-19 and most other respiratory viruses also spread from coughing and sneezing via larger respiratory droplets, which most masks do block. Masks are not perfect, but there is strong evidence that they reduce transmission.

With many hospitals at capacity, there have been questions in the media and elsewhere about whether hospitals or health care workers should prioritize the care of the vaccinated, or even refuse to care for unvaccinated individuals who develop severe COVID-19, but that’s not how we think. In medicine, especially in emergency and critical care medicine, we often care for people who make poor choices about their health. We counsel, we provide information, we hope and we press on, providing the exact same care regardless of choices or beliefs.

Although stretched thin and imperfect, we do our best for everyone who needs us. But many places have reached a point at which the demand for health care has outstripped the ability to provide it. And we need help.

Nicholas Johnson, Associate Professor of Emergency Medicine, UW School of Medicine, University of Washington

This article is republished from The Conversation under a Creative Commons license. Read the original article.

People who harbor conspiracy theories are willing to get the vaccine — as long as their friends do, too

Well before the pandemic swept the world, scientists established a strong association between having a conspirative mentality that rejects mainstream ideas and vaccine hesitancy. The more entrenched the conspiratory thinking, the more likely that person is to reject vaccines. However, even people who harbor such viewpoints can be convinced to get a COVID vaccine just as readily as those without a conspiracy mindset as long as their close circle of friends and family are pro-vaccine.

Such was the conclusion of a new study led by Kevin Winter, a senior researcher at the Social Processes Lab at the University of Tübingen, Germany. These findings suggest that friends and perhaps even the community at large can play a major role in reducing vaccine hesitancy.

Winter and colleagues were motivated to embark on this study due to the now sizable body of evidence linking conspiracy theories with anti-vax sentiment and even COVID denial. Some believe that COVID-19 is a business for health care workers and doctors are diagnosing every fever as COVID-19 for their own financial benefit.

However, there are many social, cultural, and political factors that can play a vital role in the decision-making regarding vaccine acceptance and refusal. For their own part, the researchers in Germany wondered if the influence of a conspiracy mentality can be counterbalanced by social norms.

To test this hypothesis, they conducted five studies involving over 1,200 adults from Germany, who were questioned about their attitudes towards vaccines and were assessed regarding their general conspiracy mentality.

Each study was very similar in scope and design but involved a different type of vaccine, including a hypothetical vaccine needed for traveling abroad, a hepatitis B vaccine for one’s real or imaginary child, a seasonal flu vaccine, a vaccine against the tick-borne encephalitis virus (TBEV), and a COVID-19 vaccine when available (when the study was conducted COVID vaccines were yet to be available).

In each instance, the participants had to report how inclined they were to take the vaccine in question but also estimate the extent to which their friends and families would support the vaccine.

Remarkably, the results showed that nearly for every vaccine, having loved ones that supported vaccination canceled out the relationship between conspiracy mentality and vaccine hesitancy. The only exception was the study with the flu vaccine.

“The central point of our paper is that being susceptible to conspiracy theories is not unconditionally related to lower vaccination intentions. The crucial factor is what close others think about the vaccination,” Winter told PsyPost.

“Our findings suggest that when friends and families approve of a vaccination, conspiracy beliefs no longer play a role in predicting vaccination intentions. Thus, signaling a favorable attitude towards vaccinations to close others who are prone to conspiracy theories might do the trick in reducing their vaccine hesitancy.”

“Our findings generalize across a row of different vaccinations,” Winter added. “The expectations of close others do not only play a role with regard to the COVID-19 vaccination, but also, for instance, for the willingness to get a travel vaccination.”

These findings may prove important when devising communication and outreach strategies meant to increase vaccine compliance. This is especially relevant today when in the US and most of Europe the vast majority of people who wanted a vaccine have received one, the remaining population being hesitant. Scaling this wall is rife with many challenges, though. For instance, this study is careful to note that those with deeply entrenched conspiracy worldviews rejected vaccination out of principle. These individuals may also tend to surround themselves with people who share the same values. As such, these findings only apply to people who are somewhat susceptible to conspiracies and are hesitant towards vaccination but nevertheless have friends who can steer them in the right direction.

The study appeared in the British Journal of Health Psychology.

Flu vaccine may protect against severe COVID-19

Credit: Pixabay.

Good news for the millions of people across the world still queuing for a COVID-19 vaccine. According to a new study, the flu vaccine may offer at least some protection against the worst symptoms of COVID-19. The researchers stress that this doesn’t mean that a flu shot can act as a replacement for a COVID-19 vaccine, which is your best bet against dodging the dangerous illness that forced the world to grind to a halt last year.

The researchers at the University of Miami Miller School of Medicine in the USA combed the TriNetX datasets that contain records on more than 70 million patients and identified two groups totaling 37,377. Patients from both groups were all, at some point, diagnosed with COVID-19, but those belonging to the first group had taken a flu vaccine between two weeks and six months before their diagnosis while those in the second group received no vaccine. The study period was between January 2020 and January 2021, when COVID vaccines weren’t widely available.

After accounting for factors that could affect the risk of severe COVID-19, including age, gender, smoking, and comorbidities such as obesity, diabetes, and chronic obstructive pulmonary disease, the researchers found that patients that had received a flu shot were less likely to become hospitalized or die after infection with the coronavirus.  By accounting for these numerous lifestyle differences, we believe that there is a great deal of confidence that our two groups were very similar not only in terms of medical co-morbidities and diagnoses but also in terms of their access to healthcare.

Patients who didn’t get a flu vaccine were up to 20% more likely to have been admitted to the intensive care unit, as well as 58% more likely to visit the emergency department, 45% more likely to develop sepsis, and 58% more likely to have a stroke. The risk of death, however, was not reduced.

“This dataset has millions of patients and provides cohorts with very large sample sizes, which in turn helps to validate the statistics. Our analysis demonstrates a potential protective effect of influenza vaccination in SARS-CoV-2-positive patients against adverse outcomes within 30, 60, 90, and 120 days of a positive diagnosis. Significant findings include influenza vaccination mitigates the risks of sepsis, stroke, deep vein thrombosis (DVT), emergency department (ED) & Intensive Care Unit (ICU) admissions, thus suggesting a potential protective effect that could benefit populations without readily available access to SARS-CoV-2 vaccination,” Devinder Singh, the study’s senior author and a professor of plastic surgery at the University of Miami Miller School of Medicine, told ZME Science.

More research is required to confirm this link, preferably by prospective randomized clinical trials. Although no one knows for sure yet why the flu shot provides protection against COVID-19, one theory suggests that the protective effect is owed to an enhanced innate immune system. This general immune system responds to all kinds of pathogens, new or old, unlike the adaptive immune system that is primed against specific viruses.

Previously, researchers at the University of Georgia found that the measles, mumps, and rubella (MMR) vaccine may also offer protection against COVID-19 and may partly explain why children, who typically receive this vaccine around their first birthday, are largely immune to COVID.

Although close to 50% of the population of the USA and the European Union has been vaccinated with at least one dose against COVID, in developing nations that tally currently hovers at an underwhelming 1%. In this context, flu shots may be a temporary band-aid that the global health community can use to reduce morbidity and mortality due to the pandemic until proper vaccines become accessible to all in need. Besides, having a flu vaccine offers nothing but benefits.

“Our work is important not only because limited resources around the world continue to constrain access to the COVID vaccine, but also because it may help to address concerns about vaccine development. The flu vaccine has a much longer track record of safety, and this fact may help address the hesitancy reported in some people with respect to the COVID19 vaccine. The global population may benefit from influenza vaccination as it can dually act to prevent a coronavirus and influenza ‘twindemic’ which could potentially overwhelm healthcare resources,” Singh said.

However, Singh and colleagues emphasize that they “absolutely recommend the COVID19 vaccine, and in no way suggest the flu vaccine is a substitute to the proper COVID19 vaccine.”

The findings were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The world’s first mRNA vaccine against cancer is now being trialed

After its striking success with COVID-19, BioNTech is now looking at cancer vaccines. The company has just started a Phase 2 trial of the BNT111 cancer vaccine for advanced melanoma — a vaccine that they hope will help patients fight off advanced tumors and prevent recurrencies.

Image credits: Tim Reckmann.

Before it was catapulted onto the global stage by its COVID-19 vaccine (the first widely approved vaccine developed in the pandemic, BioNTech was an early-stage biotech company firmly focused on cancer vaccines. The company planned to start both a phase 2 and a phase 3 trial of their BNT111 vaccine in 2020 — but with the pandemic coming in and BioNTech sweeping in to create not just the first COVID-19 vaccine (alongside Pfizer), but the world’s first mRNA vaccine, the plans had to be delayed — although the company can’t exactly be upset with the success.

But after the COVID-19 detour, it’s time for the company to return to its initial goal — and BioNTech seems excellently positioned to do so. Not only have they proven they can develop a quick vaccine using mRNA technology, but several mRNA vaccines targeting different types of cancers are already queued in the company’s product pipeline. Now, one of them has started Phase II trials.

The mRNA vaccine BNT111 will be tested in combination with an antibody-drug (Libtayo), targeting patients with relapsed Stage III/ IV melanoma. The vaccine is aimed at four tumor-associated antigens. Over 90% of all melanoma tumors are thought to contain at least one of these four antigens.

The Phase II trials are enrolling 120 patients from Spain, Germany, Italy, Poland, the US, the UK, and Australia after regulatory review. The first patient has now been dosed.

The company’s management appears confident in the vaccine. Özlem Türeci, Managing Director and Chief Medical Officer of BioNTech explained in a statement that BNT111 has already shown a favorable safety profile and encouraging preliminary results in early clinical evaluation. “With the start of patient treatment in our Phase 2 trial, we are encouraged to continue on our initial path to realize the potential of mRNA vaccines for cancer patients,” he added.

Previously, vaccine efficacy was assessed in a subset of 42 patients treated with the shot — either without any other treatment or alongside an anti-PD-1 drug. Out of these, 25 were treated with the vaccine alone. Out of these 25, one patient had a complete remission, three had partial remissions, and seven saw their disease stabilize. The combination group of 17 patients had six partial responses. The company is now looking to show that the mRNA vaccines can serve their intended purpose of fighting cancer.

“We were able to demonstrate the potential of mRNA vaccines in addressing COVID-19,” added Özlem Türeci, co-founder and chief medical officer of BioNTech. “We must not forget that cancer is also a global health threat, even worse than the current pandemic,” she added.

According to Türeci, preventing cancer recurrence is the “ideal setting” for mRNA technology, because after a tumor has been removed (or largely removed) through surgery, a vaccine can help produce T cells that can outnumber and control cancerous cells. Essentially, the goal is to train these T cells to recognize cancer and keep it in check.

The possibilities reach even farther, as mRNA is excellently suited for developing personalized vaccines. Because cancerous tumors can be different, BioNTech aims to be able to produce a customized vaccine within 45 days after the patient’s surgery. The idea would be to carry out a biopsy and send it to a lab, and then have a computer algorithm analyze the mutations caused by cancer, looking for the ones that trigger T cell production. But the company is also developing premade, “off the shelf” treatments, especially for people who can’t wait 45 days.

It’s harder to make a cancer vaccine than one for COVID-19, though. With COVID-19, the genetic code of the virus leads you directly to the vaccine candidate — whereas with cancer, you need to sequence the tumor’s genes and look for the useful ones. But the pandemic experience has helped the process, not just with experience, but with production infrastructure as well, Türeci told USA Today.

“I, in my wildest dreams … would never have imagined that we’d be making the quantities and quality of mRNA molecules we’re making now with. If you had told me we were going to be doing this, I’d have said you are completely crazy,” she said, praising the engineers. “Every time I think, ‘Oh my God, we can’t do any better than that,’ they surprise me.”

Whether or not the drug will be successful remains to be seen, but for now, one thing seems clear: when it comes to vaccines, mRNA is just getting started.

HPV vaccines are more effective than we assumed, for longer

Current vaccine mixes can protect for longer against more strains of HPV (human papillomavirus) than currently believed, according to new research. HPV is the most common sexually transmitted infection in the world, and it can cause cancer in women. Many countries around the world have thus set up vaccination programs in place against HPV.

HPV vaccine before being administered in Sao Paulo, Brazil, March 2014. Image credits Pan American Health Organization PAHO / Flickr.

Researchers at the German Cancer Research Center, Karolinska Institutet, and Tampere University report that our HPV vaccines are more effective than we assumed. Certain mixes of vaccine serum can immunize patients against strains other than those intended, as well, while also immunizing them for longer. While HPV infections can clear out on their own, they can become chronic and cause cancer in women.

The HPV family comprises more than 200 known strains, 13 of which are classified as high-risk (of causing cancer). Types 16 and 18 being the most threatening, causing around 70% of all cases of cervical cancer. Other strains can be more benign, with types 6 and 11, for example, causing harmless genital warts. Today, vaccines against HPV are bivalent (HPV types 16 and 18) or quadrivalent (HPV types 6, 11, 16, and 18).

The same but better

Over two studies, the researchers behind this discovery performed independent comparisons of direct and cross-protecting antibody responses, including for antibodies that protect against both vaccine HPV types and HPV types not covered by different national vaccine programs. Cross-protection refers to the mechanism by which vaccines against certain strains of HPV can immunize a patient from other strains as well, although we don’t yet have a clear idea of which vaccines these are or how reliably they can cross-immunize individuals.

The team followed 3,000 women from Finland who were vaccinated between 2002 and 2004 (they were all aged 16-17 at the time), monitoring the protection levels conferred by their (bi- and quadrivalent) vaccines over time. Samples of the serum used were also collected and held over 12 years following their use from the Finnish Maternity Cohort Biobank. The serological analyses included antibodies to 16 different HPV types.

After reviewing the numbers, the team found that women who received the quadrivalent vaccine have antibodies present in their bloodstream against the four targeted strains for up to 12 years. Those who received the bivalent serum had antibodies present in their blood for just as long, but only against two strains. However, for these latter ones, both the neutralizing and binding ability of their antibodies against HPV 16/18/31 were higher than those in women who had received the quadrivalent vaccine. This means that their antibodies were better at interacting with and preventing the virus from infecting cells.

“Our results on the correlation between vaccine efficacy and antibody positivity by HPV type explain why the bivalent HPV vaccine seems to give broader protection against different cancer-associated HPV types than previously known,” says Matti Lehtinen, a researcher at the Department of Laboratory Medicine, Karolinska Institutet, a co-author on both studies.

“The results also show that both quadrivalent and bivalent vaccines provide protection for a long time.”

The paper “Sustainability of neutralizing antibodies induced by bivalent or quadrivalent HPV vaccines and correlation with efficacy: a combined follow-up analysis of data from two randomized, double-blind, multicentre, phase 3 trials” has been published in the journal The Lancet.

The paper “Sustained Cross-reactive Antibody Responses After Human Papillomavirus Vaccinations: Up to 12 Years Follow-up in the Finnish Maternity Cohort” has been published in The Journal of Infectious Diseases.

How a CIA sham meant to hunt down Osama Bin Laden swelled antivaxx sentiment in Pakistan

Osama bin Laden. Credit: Public Domain.

In 2011, the CIA constructed an elaborate ruse involving a fake vaccination program in a town in Pakistan where Osama bin Laden was suspected to be hiding. The agency recruited a senior Pakistani doctor who, under cover of a mass immunization campaign, had to obtain DNA samples of children living in a compound in the town to confirm the location of what was then the world’s most wanted man.

The operation proved successful as the CIA found a DNA match. Bin Laden’s lair was confirmed and on May 2, 2011, a team of US Navy Seals descended on the Abbottabad compound and terminated the Al-Qaeda leader.

But bin Laden’s death did not stop extremism from spreading in Pakistan, and conservative religious movements became even more influential. Over the next three years, several terror groups — foremost among them the Pakistani Taliban — carried out bloody attacks and established strongholds in northwestern tribal areas bordering Afghanistan.

These extremist groups would also go on to exploit the CIA sham operation as ammunition for their anti-vaccination propaganda. By discrediting official, state-sponsored public initiatives, the Taliban aim to boost their own credibility. The fake vaccination program — which actually involved genuinely vaccinating a lot of people against hepatitis B, including people in a poorer part of town in order to make it look more authentic — was never authorized by Pakistani health authorities. So after it was revealed how the Americans employed vaccines to trick bin Laden’s people, the Taliban issued several edicts linking legit vaccination campaigns to CIA espionage. Later, the Taliban even used violent action against vaccination workers.

The CIA is long gone from Abbottabad but even ten years later, the repercussions of its daring operation to locate Bin Laden are still felt by the local populace. In a new study, researchers at the University of Warwick in the UK found that the vaccine ruse resulted in a significant drop in vaccination rates in Pakistan.

Using data from the Pakistan Social and Living Standards Measurement on children born between January 2010 and July 2012, the researchers investigated the effects of the disclosure of the CIA operation on vaccination rates for polio, DPT, or measles.

According to the researchers’ estimates, vaccination rates declined between 23% and 39% in districts with high levels of electoral support for parties espousing political extremism compared to districts with lower levels of support for such politics. The vaccination rate decline was higher among girls than boys.

In the context of the COVID pandemic, these mind games will likely have an even more tragic toll. Pakistan managed to limit the spread of COVID in the first and second waves, but the third wave is a different story. According to the National Command Operation Center (NCOC), over 1.8 million Pakistanis have been vaccinated at government facilities while over 18,000 received shots at private hospitals – in total, less than 1 percent of the country’s population. 

“The empirical evidence highlights that events which cast doubt on the integrity of health workers or vaccines can have severe consequences for the acceptance of health products such as vaccines,” said Andreas Stegmann, one of the paper’s authors. “This seems particularly relevant today as public acceptance of the new vaccines against Covid-19 is crucial to address the pandemic.”

The findings appeared in the Journal of the European Economic Association.

You didn’t have side effects to the COVID vaccine. But does that mean you’re less protected?

All vaccines have side effects, and our COVID vaccines developed in record time are no exception. Many of the common side effects you experience after vaccination, such as fever or nausea, are actually because our immune system is doing its thing. They’re the best indication that your immune system is getting pounded and trained, so it’s ready to face the coronavirus ‘in the field’ if the opportunity presents itself.

But since you might have had no side effects following your COVID vaccine, does this mean you’re less protected against the coronavirus? Not at all.

Credit: Pixabay.

According to Pfizer’s clinical trial, 50% of the participants did not experience any significant side effects, yet more than 90% developed immunity against the virus. Likewise, the Moderna vaccine causes side effects in only one in ten people, yet the vaccine had a 95% efficacy. Possible reactions to vaccines include headache, fever, injection site pain, muscle and joint pain, and fatigue.

These stats clearly show that a lack of side effects doesn’t mean you are less immune than those who experience side effects. The reason why some people develop side effects while others are spared has to do with the way our immune system develops immunity against viruses.

The vast majority of authorized COVID vaccines prime the immune system by inserting a piece of viral protein found on the outer envelope of the coronavirus, known as the spike protein. This protein alone cannot infect or make you sick. However, a branch of the immune system known as innate immunity will be immediately activated by the protein. The mechanisms of the innate immune system include physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body. This rapid response initiates inflammation, which is often felt as fever and pain.

So, it is due to this innate immune response that some people developed common side effects a day or two after receiving their jab. These resolve in three days tops.

You shouldn’t be worried if you don’t have any of these side effects because the aim of any vaccine is to provide long-lasting immunity and this is achieved solely by activating another branch of immunity: adaptive immunity.

Adaptive immunity does not trigger inflammation, although it may contribute to it significantly if it is already occurring for other reasons. In other words, you can be immune and perfectly protected against the coronavirus without any outward sign that your immune system is primed.

Adaptive immunity does not trigger inflammation, although it may contribute it significantly if it already present for other reasons. In other words, you can be immune and perfectly protected against the coronavirus without any outward sign that your immune system is primed.

Why some people are more likely to have vaccine side effects

Some demographics are more prone to vaccine side effects than others. Those aged 65 or older, for instance, are known to have fewer vaccine-related side effects. This may be due to the gradual age-related decline in immune activity.

A person’s biological sex can also play a role. According to a CDC study published earlier this year, 79% of the reported side effects following COVID vaccination were among women. Scientists think this could be due to the dampening effect of testosterone on inflammation, thereby reducing common symptoms like fever and pain.

Likewise, people suffering from certain conditions, such as rheumatoid arthritis or multiple sclerosis, who have to take immunosuppressive medication, may experience fewer side effects due to the dampened immunity.

But regardless of sex or the use of immunosuppressants, the COVID vaccines — and all vaccines in general — should provie immunity against viral infection despite the apparent lack of side effects. 

A game-changer on the horizon: Researchers develop the world’s most effective malaria vaccine

A vaccine against malaria has proven to be 77% effective in trials in Africa and could be a major breakthrough against the disease, according to its developers from the Jenner Institute at the University of Oxford.

Image credit: Wikipedia Commons

Malaria kills over 400,000 people every year, mostly small children in sub-Saharan Africa; one child dies from the disease every two minutes, according to the World Health Organization (WHO). Although many vaccines have been trialed over the years, none has been sufficiently successful.

A parasitic disease, malaria is transmitted through the bite of female Anopheles mosquitoes. It is both preventable and treatable. The African region was home to 94% of all malaria cases and deaths in 2019, according to the WHO. In recent years, countries have made progress using new tools such as insecticide-treated mosquito nets.

The Oxford vaccine, known as R21, is the first one to meet the WHO goal of 75% efficacy against the mosquito-borne parasite disease. The previously developed Mosquirix vaccine, now being piloted by the WHO in four countries in Africa, was partially effective, preventing 39% of malaria cases among small children in Africa over four years. A 75% efficacy could be a game changer.

“These are very exciting results showing unprecedented efficacy levels from a vaccine that has been well-tolerated in our trial programme,” Halidou Tinto, the trial’s principal investigator, said in a statement. “We look forward to the upcoming Phase III trial to demonstrate large-scale safety and efficacy data for a vaccine that is greatly needed in this region.”

Trialed in 450 children between the ages of five and 17 months in Burkina Faso, the vaccine was found to be safe and showed “high-level efficacy” over 12 months of follow-up. The children were divided into three groups and the higher dose one was 77% less likely to get the disease, the researchers reported in a pre-print study in The Lancet.

There were “no serious adverse events related to the vaccine,” the researchers wrote in the study. Now, together with their commercial partners the Serum Institute of India and drugmaker Novavax, they are recruiting for a Phase III trial to assess the safety and efficacy of the vaccine in 4,800 children, aged from five to 36 months.

Adrian Hill, director of the Jenner Institute, where the Oxford/AstraZeneca Covid vaccine was recently invented, told The Guardian that the vaccine has the potential to cut the death toll from malaria significantly. Even going from the 400,000 annual deaths to “tens of thousands” in the next five years, if the vaccine proves successful.

Hill said the institute will likely apply for emergency approval for the malaria vaccine just as it did for the COVID-19 jab. “Malaria kills a lot more people than Covid in Africa, so you should think about emergency-use authorization for a malaria vaccine,” he said. The institute will first ask regulatory bodies for a scientific opinion on the vaccine.

The researchers said the vaccine will be manufactured on a large scale and low cost. They have already done a deal with the Serum Institute of India, which is involved in manufacturing the Oxford/AstraZeneca Covid-19 vaccine. The Serum Institute promised to deliver 200 million doses a year of the malaria vaccine if it’s licensed.

Cyrus Poonawalla and Mr Adar Poonawalla, Chairman and CEO of the Serum Institute of India said in a statement: “We are highly excited to see these results on a safe and highly effective malaria vaccine. Serum Institute is committed to global disease burden reduction and disease elimination strategies by providing high volume, affordable vaccines.”

Personalized cancer vaccine shows efficacy against multiple cancers in early tests

A personalized cancer vaccine prototype has shown great promise in a phase 1 trial against different types of cancer, including some that have a high risk of reappearing.

Image credits Arek Socha.

I’m not sure if everybody here is old enough to remember this, but there used to be a time when “finding the cure to cancer” was seen as the be-all-end-all of human ingenuity. Back when my family was still toying with the idea of sending me off to medical school, my grandparents would cheer me on saying that maybe I’ll be the one to discover it — with everybody sharing the silent knowledge that such a wonder would not be possible in our lifetime. So it’s a very surreal experience to see just how far along we’ve come towards that goal.

A new paper reports that personalized vaccines against cancers — compounds created from the genetic data of individual patients and their tumors — are effective against the disease, safe to use, and show promise against commonly recurring cases.

Individually tailored

“While immunotherapy has revolutionized the treatment of cancer, the vast majority of patients do not experience a significant clinical response with such treatments,” said study author Thomas Marron, MD, Ph.D., Assistant Director for Early Phase and Immunotherapy Trials at The Tisch Cancer Institute and Assistant Professor of Medicine at the Icahn School of Medicine at Mount Sinai.

“Cancer vaccines, which typically combine tumor-specific targets that the immune system, can learn to recognize and attack to prevent recurrence of cancer. The vaccine also contains an adjuvant that primes the immune system to maximize the efficacy.”

This class of vaccines was developed with help from the Mount Sinai computational platform OpenVax, created by a group which “develops open-source software for designing personalized cancer vaccines”. In order to create these personalized vaccines, Dr Marron and his team sequenced tumor and germline DNA, alongside tumor RNA, from each patient. They also used this data to help predict whether each individual’s immune system would recognize the vaccine’s targets or not.

For the trial, the participants received 10 doses of the personalized vaccine over a six-month period after undergoing any standard cancer treatment (for example surgery). It was administered alongside an immunostimulant (or an ‘adjuvant’). This adjuvant, poly-ICLC, is a synthetic, stabilized, double-stranded RNA capable of activating multiple innate immune receptors, making it the optimal adjuvant for inducing immune responses against tumor neoantigens,” said study author Nina Bhardwaj.

Thirteen participants received the prototype vaccine. Out of them, 10 had been diagnosed with solid tumors, and 3 had multiple myeloma. All of them had, statistically speaking, a high chance of seeing a resurgence of the disease following treatment.

However, after a mean follow-up interval of 880 days, four of the participants were still cancer-free, four were receiving subsequent lines of therapy, four had died, and one chose to not continue the trial. The vaccine was tolerated well upon administration, with only one-third of the participants developing minor reactions

“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” said Dr. Bhardwaj.

“We have therefore developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, […] when patients have minimal — typically microscopic — residual disease. Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types.”

The most exciting area of the finding relates to types of cancer that have a high risk of recurrence, such as lung and bladder cancers. Personalized vaccines could finally give us a safe and efficient means of fighting them, and preventing them from reforming.

Still, these results were from a phase 1 trial, whose main aim is to determine whether a drug candidate is safe to use. While the potential benefits of the compound were noticed, determining how best to administer it for the greatest effect is the object of the phase 2 trial — meaning, we’ll have a good idea of what this vaccine can and can’t do quite soon.

The findings have been presented during Week 1 of the virtual AACR Annual Meeting 2021, held April 10-15.