Tag Archives: immunology

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.

Masks made of ostrich cells make COVID-19 glow in the dark

In the two years that SARS‑CoV‑2 has ravaged across the globe, it has caused immeasurable human loss. But we as a species have been able to create monumental solutions amidst great adversity. The latest achievement involves a standard face mask that can detect COVID-19 in your breath, essentially making the pathogen visible.

A COVID-19 sample becomes apparent on a mask filter under ultraviolet light. Image credits: Kyoto Prefectural University.

Japanese researchers at Kyoto Prefectural University have created a mask that glows in the dark if COVID-19 is detected in a person’s breath or spit. They did this by coating masks with a mixture containing ostrich antibodies that react when they contact the SARS‑CoV‑2 virus. The filters are then removed from the masks and sprayed with a chemical that makes COVID-19 (if present) viewable using a smartphone or a dark light. The experts hope that their discovery could provide a low-cost home test to detect the virus.

Yasuhiro Tsukamoto, veterinary professor and president of Kyoto Prefectural University, explains the benefits of such a technology: “It’s a much faster and direct form of initial testing than getting a PCR test.”

Tsukamoto notes that it could help those infected with the virus but who show no symptoms and are unlikely to get tested — and with a patent application and plans to commercialize inspection kits and sell them in Japan and overseas within the next year, the test appears to have a bright future. However, this all hinges on large-scale testing of the mask filters and government approval for mass production. 

Remarkably, this all came with a little help from ostriches.

The ostrich immune system is one of the most potent on Earth

To make each mask, the scientists injected inactive SARS‑CoV‑2 into female ostriches, in effect vaccinating them. Scientists then extracted antibodies from the eggs the ostriches produced, as the yolk transfers immunity to the offspring – the same way a vaccinated mother conveys disease resistance to her infant through the placenta. 

An ostrich egg yolk is perfect for this job as it is nearly 24 times bigger than a chicken’s, allowing a more significant number of antibodies to form. Additionally, immune cells are also produced far more quickly in these birds—taking a mere six weeks, as opposed to chickens, where it takes twelve.

Because ostriches have an extremely efficient immune system, thought to be the strongest of any animal on the planet, they can rapidly produce antibodies to fight an enormous range of bacteria and viruses, with a 2012 study in the Brazilian Journal of Microbiology showing they could stop Staphylococcus aureus and E. coli in their tracks – experts also predict that this bird will be instrumental in fending off epidemics in the future.

Tsukamoto himself has published numerous studies using ostrich immune cells harvested from eggs to help treat a host of health conditions, from swine flu to hair loss.

Your smartphone can image COVID-19 with this simple test

The researchers started by creating a mask filter coated with a solution of the antibodies extracted from ostriches’ eggs that react with the COVID-19 spike protein. After they had a working material, a small consort of 32 volunteers wore the masks for eight hours before the team removed the filters and sprayed them with a chemical that caused COVID-19 to glow in the dark. Scientists repeated this for ten days. Masks worn by participants infected with the virus glowed around the nose and mouth when scientists shone a dark light on them.

In a promising turn, the researchers found they could also use a smartphone LED light to detect the virus, which would considerably widen the scope of testing across the globe due to its ease of use. Essentially, it means that the material could be used to the fullest in a day-to-day setting without any additional equipment.

“We also succeeded in visualizing the virus antigen on the ostrich antibody-carrying filter when using the LED ultraviolet black light and the LED light of the smartphone as the light source. This makes it easy to use on the mask even at home.”

To further illustrate the practicability of the test, Tsukamoto told the Kyodo news agency he discovered he was infected with the virus after he wore one of the diagnostic masks. The diagnosis was also confirmed using a laboratory test, after which authorities quarantined him at a hotel.

Next, the team aims to expand the trial to 150 participants and develop the masks to glow automatically without special lighting. Dr. Tsukamoto concludes: “We can mass-produce antibodies from ostriches at a low cost. In the future, I want to make this into an easy testing kit that anyone can use.”

New COVID variant identified in France — but experts say we shouldn’t fear it

Scientists have identified a previously unknown mutant strain in a fully vaccinated person who tested positive after returning from a short three-day trip to Cameroon.

Academics based at the IHU Mediterranee Infection in Marseille, France, discovered the new variant on December 10. So far, the variant doesn’t appear to be spreading rapidly and the World Health Organization has not yet labeled it a variant of concern. Nevertheless, researchers are still describing and keeping an eye on it.

The discovery of the B.1.640.2 mutation, dubbed IHU, was announced in the preprint server medRxiv, in a paper still awaiting peer review. Results show that IHU’s spike protein, the part of the virus responsible for invading host cells, carries the E484K mutation, which increases vaccine resistance. The genomic sequencing also revealed the N501Y mutation — first seen in the Alpha variant — that experts believe can make COVID-19 more transmissible.  

In the paper, the clinicians highlight that it’s important to keep our guard and expect more surprises from the virus: “These observations show once again the unpredictability of the emergence of new SARS-CoV-2 variants and their introduction from abroad,” they write. For comparison Omicron (B.1.1.529) carries around 50 mutations and appears to be better at infecting people who already have a level of immunity. Thankfully, a growing body of research proves it is also less likely to trigger severe symptoms.

Like many countries in Europe, France is experiencing a surge in the number of cases due to the Omicron variant.

Experts insist that IHU, which predates Omicron but has yet to cause widespread harm, should not cause concern – predicting that it may fade into the background. In an interview with the Daily Mail, Dr. Thomas Peacock, a virologist at Imperial College London, said the mutation had “a decent chance to cause trouble but never really materialized. So it is definitely not one worth worrying about too much at the moment.”

The strain was first uploaded to a variant tracking database on November 4, more than two weeks before Omicron was sequenced. For comparison, French authorities are now reporting over 300,000 new cases a day thought to be mostly Omicron, with data suggesting that the researchers have identified only 12 cases of IHU over the same period. 

On the whole, France has good surveillance for COVID-19 variants, meaning health professionals quickly pinpoint any new mutant strains. In contrast to Britain, which only checks three in ten cases for variants. The paper’s authors state that the emergence of the new variant emphasizes the importance of regular “genomic surveillance” on a countrywide scale.