Tag Archives: aids

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.

‘Kick and kill’ approach cures HIV in 40% of mice

New research on mice is paving the way against the human immunodeficiency virus (HIV), the cause of AIDS.

Image via Pixabay.

Although the team did not manage to completely eliminate the virus from all the mouse hosts, they showcase an effective way of engaging with it. According to the results, the approach eliminated the virus from 40% of the mice used in the study. With more work to perfect it, such an approach could one day form the basis of an effective and reliable treatment against HIV.

Cornerstone

Currently, people infected with HIV have the option of using antiretroviral therapy to slow down the virus’ progression. However, we have no way to attack the pathogen and clear it out of a victim’s body. HIV can infect human immune cells — helper T cells, or ‘CD4+ T’ cells, to be precise — and lay dormant within them. Although our bodies have the ability to destroy HIV, this process leaves it hidden and protected from our immune response — because it’s in the cells that largely direct that response.

Any effective strategy against the virus, then, should start with forcing the virus out of hiding. This is the first part of the so-called “kick and kill” strategy, which was piloted by the same researchers that led the present study — a team at the University of California, Los Angeles — back in 2017.

In the last few years, the team has refined their approach. In 2017, they were able to clear HIV from 25% of the mice they worked with; in the present study, they report eliminating it from 40% of the mice, an almost double success rate.

The process involved first administering antiretrovirals to the mice, together with a synthetic molecule known as SUW133. This duo forces HIV out of the cells it is hiding in throughout the body. SUW133 in particular works to activate the virus in infected cells; up to one quarter of infected cells died during the time SUW133 forced this activation process to happen, the team explains.

The next step consisted of giving the treated mice injections with natural, healthy cytotoxic T white cells, which would go on and kill infected cells and virus particles.

In order to test the effectiveness of their approach, the team investigated the spleens of each mice. This organ is a common hiding place for HIV-positive cells. If no HIV was detected here, the team concluded that it had been successfully eliminated from the animal’s body.

The team notes that the compounds above worked better in combination than they did when administered independently.

Their goal for the future is to eliminate HIV from all the mice in their experiments and then progress their research into the preclinical stage by performing the same procedure on nonhuman primates, which better resemble human biology.

As of 2020, 38 million people worldwide are infected with HIV, and almost 36 million have already lost their lives to AIDS and related complications.

The paper “Latency reversal plus natural killer cells diminish HIV reservoir in vivo” has been published in the journal Nature Communications.

STEM cells could lead the way towards an effective cure against HIV/AIDS

Stem cells might finally give us the tools to fight off the human immunodeficiency virus (HIV), the pathogen responsible for AIDS, according to a new paper. Although the findings are still quite early, and based on an animal model, the authors are confident that the findings will translate well to human biology.

Image credits Miguel Á. Padriñán.

Researchers at the University of California Davis report that a specialized type of stem cell — mesenchymal stem cells (MSCs) — can boost the body’s immune response against SIV, the simian immunodeficiency virus, in primates. SIV is the equivalent of HIV but only infects non-human primates.

The discovery, they explain, makes it possible for us to establish a realistic roadmap for a multi-pronged HIV eradication strategy.

STEMing the infection

“Impaired immune functions in HIV infection and incomplete immune recovery pose obstacles for eradicating HIV,” said Satya Dandekar, senior author of the paper and the chairperson of the Department of Medical Microbiology and Immunology at UC Davis. “Our objective was to develop strategies to boost immunity against the virus and empower the host immune system to eradicate the virus”.

“We sought to repair, regenerate, and restore the lymphoid follicles that are damaged by the viral infection.”

Lymphoid tissue in the gut is a key site for HIV replication during the early stages of an infection, the team explains, and later forms viral reservoirs that make removing the pathogen very difficult. Previous research has shown that once it gets a foothold here, HIV causes a severe decrease in immune cells in the gut’s mucosal tissues (its lining) and attacks its epithelial barrier lining, causing a leaky gut.

This lymphoid tissue houses structures known as follicles, whose job is to mount long-term counterattacks against pathogens in our bodies by producing antibodies against them. This, unfortunately, means that an HIV infection impairs the same structures that are meant to defeat it.

Antiretroviral drugs are effective in suppressing HIV’s ability to replicate, but they don’t repair the damage the virus already caused to these follicles. So they can keep the infection suppressed, but on their own, they can’t form an efficient treatment against the disease.

However, the team reports that bone marrow-derived MSCs can. They carried out their experiment using a rhesus macaque model that had impaired immunity and disrupted gut functions due to an SIV infection. These cells were able to modulate, alter, and remodel the damaged mucosal site — in essence, they could repair the virus-caused damage.

“We are starting to recognize the great potential of these stem cells in the context of infectious diseases. We have yet to discover how these stem cells can impact chronic viral infections such as AIDS,” Dandekar said.

Following the procedure, the authors saw a rapid rise in antibodies and immune T cell levels, both of which engaged with the infection.

Ideally, such approaches would be used in conjunction with current HIV treatments. They can repair our bodies’ natural defenses, while antiretroviral compounds keep the infection in check. That being said, the MSCs were able to improve the hosts’ response against the infection even by themselves.

The paper “Gut germinal center regeneration and enhanced antiviral immunity by mesenchymal stem/stromal cells in SIV infection” has been published in the journal JCI Insight.

We finally have a vaccine that works against HIV (in early tests)

Hope against HIV, the human immunodeficiency virus, is closer than any time before. A new vaccine against this virus has shown promise in Phase 1 trials, leading to the production of efficient antibodies in 97% of participants.

Image credits Asian Development Bank / Flickr.

HIV and AIDS, the condition it causes, are undoubtedly some of the most terrifying medical diagnoses one can hear today. Not only the horrendous symptoms, but also the fact that they’re incurable, make them so. But perhaps not incurable for much longer, as new research shows a promising way forward against this deadly disease and the pathogen that causes it.

Immunity at last

“We and others postulated many years ago that in order to induce broadly neutralizing antibodies (bnAbs), you must start the process by triggering the right B cells – cells that have special properties giving them potential to develop into bnAb-secreting cells,” explained Dr William Schief, a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center, where the vaccine was developed.

“In this trial, the targeted cells were only about one in a million of all naïve B cells. To get the right antibody response, we first need to prime the right B cells. The data from this trial affirms the ability of the vaccine immunogen to do this.”

This vaccine, the product of a collaboration between the Scripps Research institute and non-profit IAVI draws on a novel vaccination approach to help patients develop antibodies against HIV. This approach involves triggering “naive B cells” in our bodies to produce broadly neutralizing antibodies that, in turn, fight the pathogen. It is hoped that these ‘bnAbs’ can attach to proteins called spikes alongside the surface of the HIV virus. These spikes stay very similar in structure and function across different strains of the pathogen, meaning the vaccine could be broadly efficient against it.

This ability to function across strains is a major selling point of this vaccine. HIV affects over 38 million people worldwide but a cure has not yet been forthcoming because the virus has a very fast mutation rate, meaning it can adapt to our immune system and traditional treatment approaches.

The vaccine is meant to be the first in a multi-step vaccination program that aims to coax our bodies into producing a wide range of bnAbs’s, potentially helping against other viruses that have been eluding us so far, according to Europeanpharmaceuticalreview.

The Phase 1 trial included 48 healthy adults who received either a placebo or two doses of the vaccine compound along with an adjuvant developed by GlaxoSmithKline. By the end of the trial, 97% of the participants in experimental groups (i.e. that didn’t receive a placebo) had the desired type of antibody in their bloodstream.

This is the first time we’ve been successful in inducing secretion of broadly-neutralizing antibodies against HIV, the team explains, with lead investigator Dr. Julie McElrath, senior vice president and director of Fred Hutch’s Vaccine and Infectious Disease Division calling it “a landmark study in the HIV vaccine field”.

“This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens as well,” says Dr Schief.

“With our many collaborators on the study team, we showed that vaccines can be designed to stimulate rare immune cells with specific properties and this targeted stimulation can be very efficient in humans. We believe this approach will be key to making an HIV vaccine and possibly important for making vaccines against other pathogens.”

Needless to say, since this was only a Phase 1 trial, we’re still a considerable way away from seeing this vaccine in a shot. However, the results do pave the way towards a Phase 2, and (hopefully) a Phase 3 for the drug. For the next step, the team is going to collaborate with biotechnology company Moderna to develop and test an mRNA-based vaccine for the same task as their current compound — if successful, this would considerably speed up the process.

Still, for now, the compound works as a proof of concept. It shows that our immune systems can be primed and prepared to face even terrifying pathogens. “This clinical trial has shown that we can drive immune responses in predictable ways to make new and better vaccines, and not just for HIV. We believe this type of vaccine engineering can be applied more broadly, bringing about a new day in vaccinology,” concludes said Dr. Dennis Burton, professor and chair of the Department of Immunology and Microbiology at Scripps Research, scientific director of the IAVI Neutralizing Antibody Center and director of the NIH Consortium for HIV/AIDS Vaccine Development.

The same approach can also be used to try and create new vaccines for other stubborn diseases like influenza, dengue, Zika, hepatitis C, and malaria, the team adds.

End of AIDS in sight — existing treatment prevents transmission of HIV

A groundbreaking advancement has been made in the fight against HIV: a study on HIV-carrying men found that the risk of viral transmission is zero if the virus is suppressed by antiretrovirals. The study suggests that offering proper treatment to everyone carrying HIV would end virtually all HIV transmission.

HIV-infected T cell. Image credits: NIAID.

The landmark European study followed nearly 1,000 gay male couples, where one partner had HIV and the other was taking antiretroviral drugs to suppress it. The couples had sex without condoms or other forms of protection. After eight years of medical checks and follow-ups, the study found no HIV transmission at all within couples.

A key point of the study was the fact that it did find HIV infections in 15 men among the 972 gay couples, but genetic analysis showed that their infections were with strains of HIV from another sexual partner. In other words, people did contract HIV, but only from partners who had not taken the antiretroviral treatment.

“Our findings provide conclusive evidence for gay men that the risk of HIV transmission with suppressive ART is zero,” said Alison Rodger, a professor at University College London who co-led the research.

Rodgers could barely contain her enthusiasm for the results, saying that it represents a huge step forward for HIV-infected people.

“It’s brilliant – fantastic. This very much puts this issue to bed,” said Prof Alison Rodgers from University College London, the co-leader of the paper published in the Lancet medical journal.

“This powerful message can help end the HIV pandemic by preventing HIV transmission, and tackling the stigma and discrimination that many people with HIV face,” she continued.

Of course, while this shows that an end to HIV transmissions might be in sight, actually achieving that goal is a whole different ball game. HIV and AIDS are currently in a rather weird phase. Since the epidemic began in the 1980s, more than 77 million people have become infected with HIV, and almost half of them have been killed by it. There is no true cure to eliminate the virus, but antiretroviral treatments have become very efficient at keeping it under control. Out of the people taking proper treatment, 97% have an undetectable level of the virus, meaning they cannot pass it further. However, the number of new infections stubbornly remains at around 1.8 million cases worldwide per year. Furthermore, there are significant concerns regarding the virus potentially developing resistance to current treatments.

It seems that HIV might be entering a make-or-break phase. While this study offers renewed hope to contain the virus, there’s still a long way to go and we need sustained efforts to be able to finally deal with this devastating virus.

A third patient might also be HIV-free

After the Berlin Patient and the London Patient, a third patient might also be HIV-free following a transplant: the Düsseldorf patient.

HIV Free

More than 10 years ago, medical researchers in Berlin made headlines with the announcement that for the first time in history, an HIV patient appeared to have been virus free following a stem cell transplant (via bone marrow) meant to treat a separate condition — leukemia.

Since then, no one has ever managed to eliminate the HIV virus until very recently: a few days ago, researchers announced that another patient, this time in London, also managed to get rid of the virus, also following a stem cell transplant meant to treat a different condition. Although doctors were skeptical to use the word ‘cure’, the second patient has been HIV-free for 18 months and counting.

Credits: NIH.

Now, a separate group of researchers has announced a third instance: the Düsseldorf patient. The Düsseldorf patient has been announced at the Conference on Retroviruses and Opportunistic Infections in Seattle. This patient has only been HIV-free for 3.5 months and therefore calls for even more skepticism. However, being off of antiviral drugs and HIV-free is still a promising accomplishment, even if more time is necessary for proper confirmation.

A cure?

With three patients becoming HIV-free after undergoing the same type of transplant, this is no longer a coincidence and the word cure flows almost naturally — but this is by no means a scalable treatment.

There are several common denominators for all three patients, all of which offer little in the way of scalability. For starters, there are two main variants of HIV, one of which is much rarer than the other — and all three patients had the rare variant. Secondly, they were all ‘cured’ following a bone marrow transplant, which is not only difficult and painful but also very risky. The three patients suffered from another serious condition which justified the bone marrow transplant. Most HIV patients are not suitable at all for a bone marrow transplant — it’s usually recommended as a last-ditch effort to fight cancer. Lastly, the marrow donors had a particular mutation which eliminated HIV’s ability to attach to host cells.

Essentially, the HIV patients needed the bone marrow transplant to fight cancer, not HIV — and they got really lucky. This is not a large scale cure by any means. But that doesn’t mean that researchers can’t use these rare cases and adapt them.

Invigorating the HIV fight

There have been many advancements in the fight against HIV, but there’s still no cure in sight. The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs in an attempt to keep the infection at bay. This has been successful in most parts of the world, dramatically increasing HIV survivability. HIV has become a chronic condition in which progression to AIDS is increasingly rare.

However, there are also growing concerns regarding current treatments. Drug resistance is one of the main concerns. Some viruses have exhibited the natural ability to develop drug-resistance and people not taking antiretrovirals properly can help speed up that process and pass drug-resistant strains to others. The drugs can also have serious negative side effects.

Lastly, while treatment costs have gone down dramatically, cost is still a crucial issue in some parts of the world. For instance, combination therapy has been introduced in South Africa for as little as $10 per patient per month, but a similar treatment might cost over $20,000 in the US, and countries that need the treatment the most are least able to afford it.

So researchers hope that they can learn something from these rare cases and adapt it to a scalable treatment. Replicating the HIV-eradicating effects seen in the Berlin Patient has been attempted several times, but confirmation has been lacking until now. It’s still early days, but with the results being confirmed, this opens up a promising avenue for finally eliminating HIV. We’re not there yet, but we’re zooming in.

There are currently around 37 million people living with HIV worldwide, and the virus claims around 1 million lives annually.

Defeating HIV: second patient in history goes into sustained remission after stem cell transplant

After the famous ‘Berlin patient’ ten years ago, a second person has now experienced remission from HIV. After a stem cell transplant (intended to treat cancer), the patient appeared to be HIV-free and has remained so for 18 months so far. The patient, whose case is presented in the journal Nature, is a man in the UK who has chosen to remain anonymous.

It’s a case of the “happy side effect” in a very unfortunate situation: after the patient was diagnosed with HIV in 2002, he was also diagnosed with advanced Hodgkin’s lymphoma in 2012. To treat the cancer, researchers at the University of Cambridge and University of Oxford carried out a stem cell transplant. However, just like in the case of the ‘Berlin patient’, the stem cell transplant came from donors with a protein mutation known as CCR5. HIV uses the protein to enter immune cells, but the mutated version renders the virus unable to attach itself to the cell walls — essentially protecting the body from the HIV.

The transplant proceeded without major complications. The patient also underwent chemotherapy, which can be somewhat effective against HIV as it kills cells that are dividing, but the key aspect here is the CCR5 receptor, which prevents HIV from rebounding after the treatment.

After 18 months, the patient appeared to be virus-free, although researchers are still skeptical of using the word ‘cured’.

It’s still only a sample size of two, but it’s the first time the ‘Berlin patient’ results have been replicated.

“By achieving remission in a second patient using a similar approach, we have shown that the Berlin Patient was not an anomaly, and that it really was the treatment approaches that eliminated HIV in these two people,” said the study’s lead author, Professor Ravindra Gupta (UCL, UCLH and University of Cambridge).

The study is even more exciting as reactions from the research community were very positive.

“This is good quality research and the authors used the best available technology to demonstrate with the highest degree of certainty currently possible that the patient is free of the virus,” says Prof. Áine McKnight, Professor of Viral Pathology at Queen Mary University of London.

“This is a highly significant study. After a ten year gap it provides important confirmation that the ‘Berlin patient’ was not simply an anomaly.”

Unfortunately, this is not really a scalable treatment option for HIV. Large-scale stem cell transplants would be impractical and risky. However, it represents something that might be incorporated into future treatments. Some teams are examining whether gene-therapy techniques to induce mutations on the immune system could be an option. However, there are also considerable risks, particularly when it comes to affecting other genes in detrimental ways.

Furthermore, the patient had a rare variant of HIV. There are two main variants: one uses the CCR5 co-receptor and the other uses the CXCR4 co-receptor. The vast majority of cases are in the first category, whereas this British patient fell in the second category.

“The authors clearly point out that the technique will not necessarily be effective for all HIV infected individuals, specifically those infected with CXCR4 viruses. However, the principal of targeting co-receptors may be of universal benefit,” adds McKnight.

There are currently around 37 million people living with HIV worldwide, and the only available treatment is to suppress virus — but even this treatment is only reaching 59% of the patients, and drug-resistant HIV is a growing concern. Almost one million people die annually from HIV-related causes.

“At the moment the only way to treat HIV is with medications that suppress the virus, which people need to take for their entire lives, posing a particular challenge in developing countries,” said Professor Gupta.

The study ‘HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation’ was published in Nature.

Nanoparticle HIV vaccine.

Promising new vaccine technology might finally end HIV-AIDS

A new approach seems poised to make the HIV vaccine a reality.

Nanoparticle HIV vaccine.

A model (left) of the HIV vaccine nanoparticle the team developed and its subunits (center, right).

Researchers at Scripps Research have successfully overcome past technical hurdles to creating a new HIV vaccine; the compound was shown to stimulate a powerful anti-HIV antibody response in animal models.

Enveloping attack

The team based their vaccine on a new strategy (which they describe in their paper). They drew on HIV’s envelope, Env, which is a complex, shape-shifting molecule. Env has previously thwarted vaccine-production efforts since it’s difficult to produce in vaccines in a way that induces useful immunity to HIV.

In order to stabilize Env into a shape that’s useful for the diverse strains of HIV, the team broke it down into several components. Afterward, they stitched them back together on virus-like particles (meant to mimic a whole virus). Stabilized in this fashion, the Env proteins elicited strong anti-HIV antibody responses in mice and rabbits.

“We see this new approach as a general solution to the long-standing problems of HIV vaccine design,” says principal investigator Jiang Zhu, associate professor in the Department of Integrative Structural and Computational Biology at Scripps Research.

One of the main functions of the Env molecule is to grab onto host cells and break through their membrane to initiate infection. Given its vital role, and the fact that this part of the virus has the most exposure to a host’s immune system, Env has been the main target for HIV vaccine efforts. The usual approach was to inoculate people with Env proteins (or bits of them) to coax their bodies into producing Env-binding antibodies. These antibodies would then keep HIV from infecting further cells in the future.

Up until now, that hasn’t work out. The current prevailing hypothesis is that for an HIV vaccine to be effective, it needs to present the Env proteins in a way that closely resembles the original virus. This, however, is a huge challenge. Env protrudes from the viral membrane in tight clusters of three — called trimers — which can take radically different shapes before and after infecting cells. Researchers have failed to find a broadly applicable method for stabilizing Env trimers in the pre-infection shape.

“The trimer-stabilization solutions that have been reported so far have worked for a few HIV strains but have not been generalizable,” Zhu says. “Env trimer ‘metastability’, as we call it, has really been a central problem for trimer-based HIV vaccine design.”

The team drew on Zhu’s previous work, in which he showed that altering a short section of ENV (called HR1) might force Env to stay in the pre-infection (closed) shape. The new paper shows that this strategy does indeed work for diverse HIV strains from all over the world. This “uncleaved prefusion-optimized” (UFO) approach allows researchers to produce Env trimmers in their closed shape with surprising ease and little need for purification starting from pretty standard cells (from a biotech manufacturing point of view). Zhu’s team reports successfully applying the UFO process to “30 to 40 different HIV strains” so far. In most cases, “it has worked like a charm,” Zhu says.

The researchers further refined the vaccine by genetically linking 60 such stabilized Env trimmers to individual nanoparticles that mimic the shape of a virus. The resulting vaccine molecule cannot replicate like a real virus but looks enough like one to the immune system to coax it into action.

Lab tests on mice showed that treatment with these faux viruses led to the production of antibodies that successfully neutralized HIV in only eight weeks. Even better, the HIV strain used to confirm the vaccine’s effectiveness was of a type that prior candidate vaccines generally have failed against.

“This is the first time any candidate HIV vaccine has induced this desired type of antibody response in mice,” Zhu says. Similarly unprecedented results were obtained in rabbits, demonstrating that the nanoparticle-based approach is clearly superior to the use of isolated Env proteins — it elicits a significantly stronger response and does so much more quickly.

Further tests are now underway in 24 monkeys at the National Institutes of Health-sponsored Southwest National Primate Center in San Antonio, Texas.

“We’re now testing two candidate vaccines based on Env trimers from different HIV strains, plus a third candidate vaccine that is a cocktail of three Env-based vaccines,” says Ji Li, CEO of Ufovax, a startup company that has licensed Zhu’s vaccine technology. “We think this new approach represents a true breakthrough after 30 years of HIV vaccine research.”

The paper “HIV-1 vaccine design through minimizing envelope metastability” has been published in the journal Science Advances.

HIV sexual transmission recorded live as the virus crosses the genital mucus membrane

Credit: Pixabay.

For a long time, scientists have presumed that HIV infects hosts through sexual transmission by crossing the genital mucous membranes. However, it’s one thing theorizing a model, and another thing actually seeing the process in action. Now, for the first time, researchers in France have shown live how the virus infects immune system cells in an in-vitro model of the urethral mucosa.

Morgane Bomsel, a molecular biologist at the Institut Cochin (INSERM, CNRS, Paris Descartes University), along with colleagues, introduced an infected T cell into the urethral mucosa. The cell was tagged with a fluorescent-green protein in order to track its progress. Bomsel and colleagues then recorded how the T cell came into contact with the epithelial cell of the membrane when a virological synapse formed.

In the videos, you can see how this encounter spurs production of the infectious HIV virus, seen as green fluorescent dots. Then, like the neon green ray of a blaster gun in some B-grade SciFi movie, the virus sheds across the synapse into the mucosal epithelial cell.

This video shows a top view of an HIV-infected cell (green) in contact with the urethral epithelium and beginning to form a burst of viruses.

Once the virus crosses the epithelial layer via transcytosis, the HIV is engulfed by immune cells called macrophages. After an hour or two, once the virus has been produced and shed, the cell contact ends and the infected T cell moves on.

“Infected cells, once contacting the epithelium as if it is seating comfortably on it, start to spill a string of viruses like a gun does with bullets. After shedding a salve of fluorescent viruses on the mucosa that lasted a couple of hours, the infected cells decided to detach and turn away like a goodbye,” Bomsel told ZME Science.

This video shows a top view of an HIV-infected cell (green) in contact with the urethral epithelium and forming viruses. A virological synapse forms between them and virus is shed by the HIV-infected cell.

The French researcher confessed that it was “beautiful to see these populations of different kind of cells interacting together at the microscopic levels,” even though we’re talking about a pathogen as dangerous as HIV.

One of the most surprising findings, though, was that the infected T cells targeted epithelial cells directly above macrophages. This suggests there’s an interaction between the macrophages and the epithelium, which no one had predicted before.

This video shows an HIV-infected cell (green) that has already formed a synapse with an epithelial cell. The virus then starts to shed. When all the virus has been shed, the infected cell leaves.

The macrophages that consumed the HIV continue to produce and shed the virus for 20 days, after which the cells enter a latent, non-virus-producing state. However, the virus is still stored in macrophage reservoirs in the genital tissue. This explains why it’s so challenging to treat HIV. Antiretroviral therapies can keep the HIV reservoirs latent but interrupting therapy will cause the infection to rebound and continue spreading.

In light of these recent findings — which describe a precise mechanism of HIV entry and early establishment of HIV reservoirs in tissue macrophages — perhaps a vaccine active at the mucosa level could avoid an HIV reservoir formation if it is administered early upon infection.

“With our model and the detailed kinetic knowledge of how reservoirs are infected, new drugs that could potentially eradicate these reservoirs might now be established and tested,” said Bomsel.

The team of researchers is already working to find ways of purging the reservoir. They’re testing a “shock and kill” strategy where a macrophage-specific agonist is coupled to mucosal antibodies specific to the HIV surface. The plan is to activate the HIV reservoirs in the macrophages so these become visible to the immune system.

Scientific reference: Cell Reports, Real et al.: “Live imaging of HIV-1 transfer across T-cell virological synapse to epithelial cells that promotes stromal macrophage infection”.

A single injection protects monkey from HIV infections

A single injection of HIV-targeting antibodies protects monkeys from HIV infection for 20 weeks, a new study reports.

Image via Wikipedia.

Although there is still no definitive vaccine or cure for HIV, 30 years of research have brought us closer and closer to finally finding a way to kill out the virus. For instance, studies into immune responses have found that individuals with HIV can develop antibodies that block infection by a broad range of viral strains. These antibodies have been used to control the virus in patients who are already infected, and are also used to develop therapies that keep HIV at bay.

[panel style=”panel-default” title=”Antibodies” footer=””]Antibodies are proteins that the body produces to fight infections. Antibodies can attack substances that the body recognizes as alien, such as bacteria, viruses, and foreign substances in the blood. Typically, antibodies are produced to counteract a specific antigen. Antibodies can also be used in vaccinations.[/panel]

Now, Malcolm Martin of the US National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, reports that monkeys can be protected from simian HIV (SHIV) infection in the long term, by a single injection of antibodies. He and his colleagues developed an injection by modifying two HIV-neutralizing antibodies, which enabled them to survive longer in the bloodstream. As a result, the cocktail was much more effective at destroying SHIV.

Researchers report that a single injection was able to prevent infection for a median time of 20 weeks. The ability to induce durable protection from HIV is an important step forward, which could, in time, be translated to humans.

Of course, 20 weeks is not an ideal period — researchers hope to develop an injection that lasts much longer — but this lays the groundwork for developing antibodies for use as an annual or biannual pre-exposure prophylactic. In the absence of an HIV vaccine, it’s pretty much the best thing we can hope for.

This is not exactly a vaccine, though it is an injection that temporarily protects against the infection.

The development couldn’t come a moment too soon. Since 1981, AIDS has killed at least 25 million people, and an estimated 18 million people are currently infected with HIV (the real figures are probably much higher than that).

It’s not the first time an HIV vaccine has been proposed. Just days ago, researchers proposed a solution which included dormant, last-ditch antibodies to develop a new type of vaccine. In another study, five patients were reportedly HIV-free after vaccine therapy. Scientists are zooming in on a solution, step by step.

The study “A single injection of crystallizable fragment domain–modified antibodies elicits durable protection from SHIV infection” has been published

Russia on the brink of HIV crisis as AIDS denial runs rampant through the country

Less than half of Russians with HIV are taking the necessary antiretroviral drugs, in part due to a conspiracy theory that’s running rampant through the country. Basically, many Russians refuse to believe HIV and AIDS are real, instead choosing to believe that they are a myth invented by the West.

Antiretroviral Drugs to Treat HIV Infection. Credits: NIAID.

As the world marks the World Aids Day on 1 December, many people have been fooled by a cruel conspiracy theory. HIV/AIDS denialism is the belief — thoroughly contradicted by conclusive medical and scientific evidence — that the human immunodeficiency virus (HIV) does not cause acquired immune deficiency syndrome (AIDS). The conspiracy theory comes with slight variations, with some believing that HIV doesn’t exist at all, while others claiming that HIV exists but it does nothing to cause AIDS. In South Africa especially, AIDS denialism has been prevalent, with researchers attributing over 300,000 AIDS-related deaths, along with 171,000 other HIV infections and 35,000 infant HIV infections, to the South African government’s former embrace of HIV/AIDS denialism. Now, this worrying trend is picking up steam elsewhere in the world.

In Russia, 900,000 Russians are living with HIV today, with 10 new cases emerging every hour. While globally, HIV rates have been slowly going down, in Russia (and much of Eastern Europe), they are growing alarmingly fast. National health interventions have been almost non-existent, and public awareness and support are very low, as is the national trust in doctors. Within this unfortunate social situation, a pseudoscience cult has started to emerge. People often don’t even learn about proper treatment options and sometimes refuse treatment altogether.

“It’s unacceptable in our day and age that children are dying while a range of treatment is available,” said Alexey Yakovlev, head doctor of the Botkin hospital in Saint-Petersburg, where a 10-year-old girl died in August after her religious parents repeatedly refused to treat her.

HIV cases have dropped worldwide, but in some parts of the world, things are starting to get worse. Credits: NIAID.

A positive diagnosis handled badly is how denialism most often begins. Without psychological support and often seeing the diagnosis as a “you only have a few years to live” sentence, patients often turn to alcohol and drugs — but even more often, they turn to the internet. As you’ve probably happened to see in your day to day life, the internet isn’t really a regulated space where you’re guaranteed to find accurate, scientific information. Quite the contrary: proper science and pseudoscience often emerge side by side, and sometimes, all you need to convince people on the internet is scream loud enough. So instead of reading accurate information about HIV, AIDS, and treatment options, you might read that AIDS is a divine punishment or something that derives from anal sex. You might learn that you need a silver enema or to put jade eggs in your vagina. Perhaps there’s a “miracle cure,” usually something simple like a fruit. In short, you might read all sorts of crap on the internet, and when you’re under the tremendous pressure which comes with a harsh diagnosis, you might fall for it. Things only get worse when celebrities start advocating such pseudoscience.

In Russia, one such celebrity is Olga Kovekh, a former military doctor, currently employed as a physician in a clinic in Volgograd. According to The Independent, she’s expressed doubts about the existence of pneumonia, vaccines, and even suggested that TB could be treated with proper administration of ham sandwiches. Of course, she addressed HIV too, reportedly stating that HIV drugs are poison.

“One goal of the AIDS myth is decreasing the planet’s population to two billion by establishing total control” through vaccinations, she said. Along with similar-minded people, she presents HIV as an American invention, something which only happens to “druggies” and “gays.” This only helps fuel denial. If you believe the propaganda, you’re not a druggie and you’re not gay, you might have a hard time understanding how this happened to you — and like a vicious cycle, it goes on and on.

“The biggest reason (for people becoming denialists) is lack of consultation,”said Yekaterina Zinger, director of the Svecha foundation in Saint-Petersburg.. “People don’t get enough information and begin to think that somebody is hiding something from them.”

“The temptation to believe that it’s a myth is very high,” she said, especially for heterosexual people that are not in risk groups commonly associated with HIV that “don’t understand how it happened to them”.

With proper medication, many cases of HIV infection can result in normal or almost normal life expectancy years. But without it, the disease can be indeed a sentence. Russia is one of the leaders when it comes to HIV testing, with 25 million tests administered last year. But with a shortage of available treatment, and with pseudoscience running amok, the country might be on the verge of a health crisis.

Illustration of the HIV virus. Credit: Pixabay.

What’s the difference between HIV and AIDS

Most people use the terms HIV and AIDS interchangeably. Though the two are certainly connected, they mean different things.

Illustration of the HIV virus. Credit: Pixabay.

Illustration of HIV. Credit: Pixabay.

HIV is first and foremost a virus

Simply put, both HIV and AIDS are caused by the same human immunodeficiency virus but represent two different stages of the disease. Thought it might sound confusing at first, doctors, scientists, and the media use the term HIV to both describe the virus and the infection it causes. The distinction becomes clear once you understand the context the term is used in.

It’s not clear yet but the consensus seems to be that the virus appeared sometime in the late 19th or early 20th century in Western and Central Africa. The virus initially appeared in a non-human primate and was then transmitted to people after someone killed and ate the infected creature.

In the United States, AIDS was first recognized as a distinct condition in 1981 due to an increase in the incidence of rare opportunistic infections and cancers in homosexual men. There’s actually a rather freakish backstory about these early days of HIV/AIDS research. We’ve covered before the story of a Canadian flight attendant named Gaetan Dugas who for decades has been wrongly labeled as the ‘patient zero’ — the source of HIV infections in the United States. It was only recently that his name was cleared.

Typically, HIV causes flu-like symptoms two to four weeks after infection. Patients often describe the sensation as “the worst flu ever.” This short period is called the acute infection and unfortunately, many people mistake their HIV infection for the flu, making them susceptible to transmitting HIV to other persons. After the acute infection period, our immune systems temporarily bring the infection under control leading to the latency period.

During the latent period, an HIV infected person can feel no symptoms for years. Symptoms will arise once HIV infection turns into AIDS.

To diagnose HIV during the latent phase, doctors have a couple of tests at their disposal. When infected with HIV, the body produces telltale antibodies against it. Blood or saliva tests can detect these antibodies and determine whether or not a person is HIV positive. For this test to work, however, the person has to have been infected for at least a couple of weeks. If you suspect you’re infected with HIV, the wisest thing to do is to repeat the test after four weeks.

Another widely used HIV test looks for specific proteins produced by the virus called antigens. This test can accurately detect HIV mere days after infection.

HIV is transmitted through the exchange of bodily fluids.These fluids are blood, semen, pre-seminal fluids, rectal fluids, vaginal fluids, and breast milk. In the United States, HIV is spread mainly by having unprotected sex or sharing injection drug equipment, such as needles, with someone who has HIV. An infected mother can pass on the HIV infection to her child during pregnancy. Rarely, some people can become infected from a tainted blood transfusion. You can’t get HIV from skin-to-skin contact, nor is HIV spread through saliva.

AIDS is a condition

While HIV is a virus that causes an infection, acquired immune deficiency syndrome (AIDS) is a condition or syndrome caused by the HIV infection. AIDS develops after HIV does enough damage to the immune system to trigger the syndrome. AIDS is essentially the final stage of the HIV infection.

To diagnose AIDS, doctors look for certain biomarkers that signify the transition from HIV latency to AIDS. In its fight with the immune system, the virus ends up destroying immune cells called CD4 cells. Typically, a person who isn’t infected with HIV has a CD4 cell count of anywhere from 500 to 1,200. HIV patients with fewer than 200 CD4 cells are diagnosed with AIDS.

AIDS is also diagnosed indirectly when the presence of opportunistic infections is clear. These infections are diseases caused by various other viruses, fungi, or bacteria that would not normally affect a person with a healthy immune system.

Symptoms will vary from person to person because AIDS essentially means the patient has a damaged immune system that can’t fight infections well. So having AIDS makes you vulnerable to all sorts of other viruses and diseases. You can have AIDS but then easily get tuberculosis, pneumonia, certain types of cancer, and other infections. It’s these acquired diseases that eventually kill the AIDS patient, not the syndrome itself.

HIV vs AIDS at a glance

  • HIV is a virus or infection while AIDS is a condition.
  • A person could become HIV positive, but never develop symptoms.
  • You can have an HIV infection without acquiring AIDS. Thanks to modern treatments and medicine, people can live with HIV infections for years or even decades without acquiring AIDS.
  • In other words, someone with AIDS has to have the HIV virus, but someone with HIV doesn’t have to have AIDS.
  • HIV has no cure. The infection never goes away even if the patient never develops AIDS.
  • Like other viruses, HIV can be transmitted from person to person. AIDS, on the other hand, is a syndrome that is acquired only after a person gets infected with HIV.

Treatment and life expectancy

Once HIV turns into AIDS, the patient is in big trouble. Life expectancy drops significantly and the immune system is cut to shreds. Eventually, other infections or cancers kill the AIDS patient. Without treatment, a person whose infection progresses into AIDS can expect to survive no more than 3 years.

Today, however, HIV isn’t the death sentence that it used to be. Antiretroviral therapy (ART) can prevent HIV from replicating, vastly reducing the amount of virus in the body, thereby improving the resilience of the immune system. That being said, ART is not a cure for HIV but it can help patients live for many years with HIV without feeling sick. Before the introduction of ART in the mid-1990s, people with HIV could progress to AIDS in a few years. As such, ART is truly a life saver.

This therapy also reduces the risk of transmitting HIV to others. Often, doctors will recommend the partners of someone infected with HIV to take a preventive treatment called pre-exposure prophylaxis (PrEP). This treatment helps keep HIV from founding a permanent infection.

In early 2017, the FDA has approved a medication sold under the name of Truvada that can reduce the risk of HIV infection by up to 92 percent. And after decades of research and billions of dollars worth of funding, we seem to be inching in on a cure. In 2016, British researchers working at Oxford, Cambridge, Imperial College London, University College London and King’s College London claim they have developed a treatment that may have cured a 44-year-old British man of HIV. 

 

Five HIV patients are now virus-free thanks to a new vaccine therapy — but success rate is low

The new therapy gives our bodies new tools to weed out HIV without any other drugs — one man has been HIV-free for 7 months.

Image credits: NIBSC/SPL

According to the UN, 18 million people (about half of all people living with HIV) take antiretroviral medication (ART). These drugs are expensive, unavailable in some parts of the world, and usually come with very nasty side effects. Patients also have to take them every single day, in some cases for the rest of their lives. Furthermore, ART doesn’t really cure HIV, it just keeps it under control so it doesn’t wreak havoc on the body.

Three years ago, Beatriz Mothe of the IrsiCaixa AIDS Research Institute in Barcelona, Spain, started working on a new approach. She and her colleagues developed a trial in which 24 people recently diagnosed with HIV were given two vaccines developed by Tomas Hanke and his colleagues at the University of Oxford. They were also given ART, to see what kind of an immune response the vaccines trigger. Mitchell Warren, executive director of the Aids Vaccine Advocacy Coalition says that this new study, even though it’s conducted on a small sample size, could make a great difference.

“Long-term systems that don’t require daily pill taking could really help accelerate getting 37 million people with HIV undetectable and not infectious – that would be a great opportunity to turn the tide on the epidemic,” he told The Independent.

In the latest stage of the trial, 15 of them received a new treatment: a booster dose of one of the vaccines, followed by a cancer drug called romidepsin (which has been shown to stir HIV in the past). ART doesn’t kill nor cure the virus. However, when taken in combination they can prevent the growth of the virus. When the virus is slowed down, so is AIDS (the disease). But if you want to kill it, you have to convince it to go out — this is what romidepsin does.

Unfortunately, the approach proved unsuccessful for 10 participants. The virus immediately bounced back and they had to switch back to ART. But for five of them, it went really well; one patient is HIV-free without taking ART for seven months, while the other 4 have been free of detectable virus for six, 14, 19 and 21 weeks, respectively. It’s not clear why only a third of patients were responsive to the treatment, but Mothe said they are investigating it. This is still in the early stages of research, as the results haven’t even been published in a peer-reviewed paper — just presented at the Conference on Retroviruses and Opportunistic Infections in Seattle.

If their attempts prove successful, it can make a world of a difference. Costs of ART in low to middle-income countries alone was estimated to hit $19 billion in 2015 — despite only reaching half of those infected with HIV. There’s still a long way to go, but it seems like Mothe and her team are on the right path.

Medication prevents HIV/AIDS has 92% success rate, but people don’t know about it yet

A medication sold under the name of Truvada was approved by the Food and Drug Administration in 2012 to prevent HIV infection. If taken daily, the pills can reduce the risk of HIV infection by up to 92 percent.

Truvada: The pill and its commercial label and presentation as marketed in Denmark. Image credits: Fersolieslava / Wiki Commons.

In the US, the main purpose of Truvada (technically called PrEP) was to protect men who are having sex with other men. According to the CDC, they account for 83 percent of new HIV diagnoses. Previous research had already shown that the medicine is able to prevent HIV even when one of the partners is already positive, and this is confirmed in real life, according to NPR. But it’s not just men who can benefit from the drug – it can help women just as well, and organizations in Washington are trying to promote Truvada to people who don’t know they need it. African-American women especially are more at risk statistically, but most are not aware such a drug even exists.

“This is all about empowering women, especially black women, by giving them sexual health options and also embarking on a path of research,” says Linda Blout, president of Black Women’s Health Imperative, a nonprofit organization in Washington, D.C. The organization is helping to launch the capital’s first citywide program to promote use of the drug among women.

According to the CDC, African-American women make up 62% of women HIV cases, while white women account for 18 percent and Latinas for 14 percent. Most of the new HIV cases come from sexual intercourse, not from other drug or injection-related uses. For most of these women, it’s not just the lack of information, lack of empowerment is also a major issue — they just can’t ask their partners to wear a condom or to get tested.

“A lot of the issue has to do with misinformation or simply not being informed at all,” says Nancy Mahon, executive director of the MAC AIDS Fund, which is providing financial support for the effort. “When it comes to PrEP, many people still don’t even know it exists, especially heterosexuals. Many black women we’ve spoken to felt puzzled about why we were addressing how this drug is available to them. A component of the issue is that the drug is hard to obtain without a doctor.”

So we’re getting there in terms of science and the anti-HIV drugs are getting better and better. But moving things from the lab and into society is a whole new ball game. Dr. Eugene McCray, director of the CDC’s Division of HIV/AIDS Prevention says it can take up to a decade for consumers to start accepting a drug.

“The other problem here is that it generally takes five to 10 years for consumers to become socially acquainted with any drug,” McCray says. “That’s why we’re trying to push the information associated with PrEP to the communities in dire need of it.”

Revolutionary HIV vaccine to be tested on 600 people next year

HIV is still one of the most devastating diseases in human history, with 36.7 million people being infected in 2015 – including 1.8 million children. But scientists are not slumbering, and for decades they have been working on ways to attack the disease. Now, we may be zooming in on a working vaccine, as human tests are set to start next year.

Image credits: National Cancer Institute.

Scientists from Western University have revealed details about SAV001, the first preventive HIV vaccine using a killed HIV virus. So far, human tests on 33 participants have already shown that the drug has no serious adverse effects, and now, researchers are preparing for Phase II clinical trials – in other words, they are trying it on a larger group of non-HIV people to assess its effectiveness in producing anti-HIV antibodies. The good news is that this process is usually quite fast – we could have the results of this trial by next fall. If that works, then this has a lot of potential in dealing with the AIDS epidemic – a vaccine could be a game changer.

“If we can show that this vaccine is effective in preventing people from contracting HIV, we can stop the AIDS epidemic and that would be tremendous,” said project lead Chil-Yong Kang in a statement.

The vaccine works by exposing the body to an inactive, “killed” virus. In contrast, live vaccines (which are nearly always attenuated vaccines) use pathogens that are still alive. This strategy has been successful against a number of other dangerous conditions, including polio, flu, and hepatitis A. The reason this hasn’t been done before is because the HIV virus is so difficult to inactivate – it just evolves quickly and bypasses our defenses. In order to bypass this problem, researchers swapped some of the HIV genes with genetic material taken from honeybees, rendering it harmless to humans.

Still, don’t hold your breath just yet. We are still likely years away from this drug hitting the shelves because drugs like this require arduous testing to ensure that there are no negative consequences – even before the drug’s effectiveness is assessed.

“We were very excited with the phase I results,” Chil-Yong Kang added. “The trial demonstrated that our vaccine stimulates broadly neutralising antibodies that will neutralise not only single sub-types of HIV, but other sub-types, which means that you can have the vaccine cover many different strains of the virus.”

The results of that trial have been published this week in the journal Retrovirology, and we will likely see results next year.

NIH isolates new antibody which neutralizes 98% of HIV strains in lab trials

An antibody produced by an HIV-positive patient has been found to neutralize 98 percent of all HIV strains it was pitted against, including most of those resistant to other antibodies of the same class.

Orange glass antibody. Image credits Upupa4me / Flickr.

Orange glass antibody.
Image credits Upupa4me / Flickr.

Antibodies are chemical compounds produced by the immune system to deal with pathogens such as bacteria or viruses. They function by binding to them to either neutralize or flag them for disposal by white blood cells. One of the biggest hurdles our bodies have to overcome in creating an efficient HIV antibody is the virus’ ability to rapidly adapt and overcome whatever is thrown at it. So these substances usually see a limited timeframe of efficiency against the virus, after which it morphs becoming untouchable again.

But a new antibody isolated by the US National Institutes of Health (NIH) called N6 has shown it can maintain its ability to recognize HIV even as the virus changes and breaks away from it. It is also an estimated 10 times more potent than VRC01, an antibody in the same class, which has passed to phase II clinical trials on human patients after protecting monkeys against the virus for six months.

“The discovery and characterisation of this antibody with exceptional breadth and potency against HIV provides an important new lead for the development of strategies to prevent and treat HIV infection,” said Anthony S. Fauci from the US National Institute of Allergy and Infectious Diseases.

N6 was tested on 181 different strains of HIV and destroyed 98% of the samples, including 16 out of 20 strains immune to other antibodies of its class. For comparison, VRC01 is only effective against 90% of HIV strains. N6 brings not only a wider scope but also much greater potency, the researchers report.

“Of those antibodies being considered for clinical development, there are examples of antibodies that are extremely broad but moderate in potency (e.g. 10E8 or VRC01) or extremely potent and less broad (e.g. PGT121 or PGDM1400).”

“However, the discovery of the N6 antibody demonstrates that this new VRC01-class antibody can mediate both extraordinary breadth and potency even against isolates traditionally resistant to antibodies in this class.”

One size fits all

To see what makes N6 so good at overcoming the shifting defenses of the virus, the team tracked its behavior over time as it interacted with HIV. They found the antibody targets bits of the virus which stay similar throughout different strains, not those which are prone to change — such as the V5 region. By binding to this area, N6 prevents the virus from infecting the host’s immune cells — which makes HIV-positive individuals’ defenses crumble, developing into AIDS, the acquired immune deficiency syndrome.

“N6 evolved such that its binding was relatively insensitive to the absence or loss of individual contacts typically found in the VRC01 class,” the team reports.

While there are some mutations of HIV that are resistant to N6, they rarely developed. This suggests that the virus doesn’t have as much time to react to the antibody as it has with other treatments scientists are exploring.

“The rare occurrence of N6 resistance mutations suggests that such mutations come at a relatively high fitness cost, which might represent a partial barrier to the selection of resistant mutants,” they explain.

So far, N6 has only been tested in lab settings. Until the results can be re-created in vivo on live human trials, the team recommends we remain cautiously optimistic.

Of course, these results have so far only been demonstrated in the lab, so until we see the same levels of success in actual human trials, we need to remain cautiously optimistic. However, given recent breakthroughs by UK researchers, who managed to completely flush HIV out of a patient’s system and those of a German team’s gene-snipping approach, a reliable cure for HIV/AIDS may be just around the corner.

The full paper “Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth” has been published in the journal Immunity.

Drugs clear HIV from British patient’s system, offering hope for a cure

A new treatment has shown “remarkable” progress in fighting HIV, doctors report. The work is being carried out by five of Britain’s top universities — Oxford, Cambridge, Imperial College London, University College London and King’s College London — coordinated by the NHS.

Scanning electromicrograph of an HIV-infected H9 T cell.
Image credits NIAID / flickr.

A 44-year-old British man could become the first ever patient to be cured by HIV using a treatment developed by five UK universities working together. The man (who has asked to remain anonymous) is one of 50 trial patients for a new drug that can attack the virus even in its dormant form, the team reports.

The man’s blood has been tested clean of HIV, the scientists told The Sunday Times, although that could be the effect of regular treatments. The catch with the virus — and what’s made it so tricky to cure in the past — is that it can infect white T-cells, splicing itself into their DNA. Not only does this make the cells ignore the virus, but after the drugs clear a patient’s system, they actually produce more of the virus. If these infected cells were cleared out, it could prove to be the first real cure for HIV — and that’s what the team has been working on.

“This is one of the first serious attempts at a full cure for HIV,” said managing director of the National Institute for Health Research Office for Clinical Research Infrastructure Mark Samuels.

“We are exploring the real possibility of curing HIV. This is a huge challenge and it’s still early days but the progress has been remarkable.”

Currently, the most efficient treatment we have against HIV are anti-retroviral therapies (Art), which work pretty well at destroying the virus but they can’t spot the infected T-cells. The new treatment uses a two-pronged attack. First, a vaccine teaches the body how to identify HIV-infected cells so our immune system can clear them out. Secondly, a drug called Vorinostat is used to activate the dormant T-cells which start producing HIV-specific proteins, turning them into huge targets for healthy white cells.

Imperial College London consultant physician Professor Sarah Fidler said the treatment worked in the laboratory and there was “good evidence” it will work in patients. She also stressed out that just because a drug worked once doesn’t make it a treatment yet — “We are still a long way from any actual therapy,” she said.

The anonymous patient, a social worker from London, is understandably excited about the results:

“It would be great if a cure has happened. My last blood test was a couple of weeks ago and there is no detectable virus.”

“I took part in the trial to help others as well as myself. It would be a massive achievement if, after all these years, something is found to cure people of this disease. The fact that I was a part of that would be incredible.”

Only two other people have ever been cured of HIV. One is Timothy Brown, also known as The Berlin Patient, who received a stem cell transplant from a patient with natural immunity to HIV in 2008. The other, a Mississippi newborn, seemed to have been cured through anti-retroviral therapy in 2013, an undoubtedly unique case.

Hopefully, they’re just the first in what’s to become a very long list of successes.

Scientists stumble upon a vaccine which blocks HIV in monkeys – human trials planned

Scientists were surprised when they unexpectedly stumbled upon a relatively simple vaccine which blocks infection with SIV – the monkey equivalent of HIV – and stops the spread of the virus in already infected monkeys.

How it works

T-lymphocyte. Image via David Darling.

All efficient vaccines against a viral infection elicit virus-specific neutralizing antibodies and sometimes also cytotoxic T-lymphocytes (CTL) that prevent virus infection or eradicate the virus rapidly after it enters the body. So far, this has proven impossible in the case of HIV, despite huge advancements in the last couple of decades. So far, only one trial out of more than a hundred proved limited efficiency, with modest and short lasting protection.

This vaccine, which was described by researchers as ‘surprising’ and ‘unexpected’ works by stimulating the production of a previously unknown group of CD8 T-cells. T-cells are a type of white blood cells that play a crucial role in the body’s immunity. What HIV (and SIV) does is that it supressess the generation of T-cells, and stops the body from recognizing as a dangerous pathogen. This vaccine stimulates the production of a type of T-cells, while suppressing the production of others; the virus is recognized by the body as a pathogen and the body organizes a much better defense.

“Instead of activating dendritic cells by loading them ex vivo with inactivated HIV, we then investigated possibility of developing a prophylactic anti-SIV vaccine by directly stimulating mucosal dendritic cells in vivo.”, authors write in their study.

The vaccine was  based on a long standing but yet unproven theory that conventional vaccines that rely on stimulating an immune response to a microbe in advance of exposure to it could not work in HIV. The problem that HIV poses compared to other viruses is that it uses the very cells that are supposed to fight against it to reproduce. This means that if the body mounts a blind defense, which is the traditional approach for vaccines, HIV would just use the body’s defenses to reproduce. The trick they used was to make the body recognize HIV, but prevent it from launching a proliferative defense which would be used against it.

The Results

Initially, they started out with 21 monkeys which received the vaccine and 8 monkeys which received the vaccine with Lactobacillus plantarum – a common type of gut bacteria.

15 out of the 29 monkeys were completely protected even 4 years after the vaccine was given! The control group of 26 monkeys who were exposed to SIV were all still infected 4 years after. What’s even more notable is that the researchers administered the vaccine through different ways (rectal, vaginal gel and drink). While some of the monkeys who received the vaccine rectally or vaginally were not resistant to infections, all the monkeys who drank the vaccine with the gut bacteria were protected against future SIV exposure.

To be perfectly honest, scientists weren’t expecting to get such remarkable results. They were mystified to see that doing something as simple as giving inactivated SIV along with a simple probiotic preparation produced such a strong immune-suppressant response, especially as iSIV given by itself produced a more typical immune-stimulant response.

Moving on to humans

The results are so promising that they are immediately planning to move on to humans. So far, two trials are planned – in one, HIV-negative volunteers at low risk of HIV will be given the vaccine to see if it stimulates the same immune- and virus-suppressant responses. In the other one, HIV-positive volunteers on fully-suppressive antiviral therapy will be given the vaccine and then taken off ART six months later if the vaccine prompts the same response.

However, it has to be said that just because a vaccine works in monkeys it doesn’t necessarily mean it will have the same success in humans. We will have to wait for human clinical trials, and that will take quite a while (at least a couple of years); so even if everything works out just fine, we’re still a few years away from an effective HIV vaccine. However, this is exciting news, which may very well turn out to be the AIDS breakthrough we’ve been waiting for. Time and future research will tell.

Journal Reference: Jean-Marie Andrieu, Song Chen2, Chunhui Lai, Weizhong Guo and imageWei Lu. Mucosal SIV vaccines comprising inactivated virus particles and bacterial adjuvants induce CD8+ T-regulatory cells that suppress SIV-positive CD4+ T-cell activation and prevent SIV infection in the macaque model.  Front. Immunol., 30 June 2014 | doi: 10.3389/fimmu.2014.00297

Illustration of HIV virus.

Study of HIV evolution shows the virus is adapting to human hosts

Illustration of HIV virus.

Illustration of HIV virus. Photo: FDA

One of the most threatening modern pandemics, HIV/AIDS, has been thoroughly studied in the past few decades, with billions awarded to research seeking out a cure. Progress has been slow, but today doctors have a number of tools at their disposal to curve HIV development, spreading and ail patients, despite a cure has yet to be found (though hope exists for infected babies). One of the greatest challenges when dealing with viral infections such as HIV is adaptation. If the virus adapts to drugs or even a possible cure, then the researchers’ work can turn out useless. While most studies focused on exploring HIV’s capacity to adapt to drugs, a recent study from Simon Fraser University, Canada looked at how HIV adapts to its human hosts. The results show that indeed HIV is adapting to the human immune system, but this change is gradual and unlikely to affect current vaccine design.

The HIV evolution

Zabrina Brumme, an assistant professor in SFU’s Faculty of Health Sciences, led the research that characterized HIV sequences from patients dating from 1979, the beginning of the North American HIV epidemic, to the modern day. She and her team performed painstaking reconstruction work, which required the careful recovery of viral RNA from historic specimens followed by laboratory culture.

“HIV adapts to the immune response in reproducible ways. In theory, this could be bad news for host immunity—and vaccines—if such mutations were to spread in the population,” says Brumme. “Just like transmitted drug resistance can compromise treatment success, transmitted immune escape mutations could erode our ability to naturally fight HIV.”

Armed with a slew of  ancestral HIV sequences, the researchers could from there establish  the spread of immune escape mutations in the population.

“Overall, our results show that the virus is adapting very slowly in North America,” says Brumme. “In parts of the world harder hit by HIV though, rates of adaptation could be higher.”

This reproductive pattern, however, is too slow to affect current vaccine design or other treatments, which is definitely good news.

“We already have the tools to curb HIV in the form of treatment—and we continue to advance towards a vaccine and a cure. Together, we can stop HIV/AIDS before the virus subverts host immunity through population-level adaptation,” Brumme adds.

The findings were reported in the journal PLOS Genetics.

German scientists have managed to remove HIV from cells while leaving those cells alive

Using an enzyme to ‘cut out’ the virus, German researchers have managed to find remove HIV from cells, leaving the cells virtually unharmed. This has a boatload of work before it sees the light of day, but it’s the most promising HIV study I’ve read in quite a while.

Killing HIV cells, mice, and a Petri dish

The media has a way of exaggerating when it comes to disease-focused research. Any advance, any achievement that was only successful in a lab is labeled as the ‘cure for cancer’ (or HIV, or whatever). This is not a cure for HIV, at the moment; matter of fact – it may never see the light of day. But it has many good things going for it, and it just might work.

Biomedicine researchers at Dresden’s Technical University succeeded in curing several HIV-infected mice with the new method by using a specific enzyme to cut the virus off.

“There are various methods and similar approaches, but removing the virus from infected cells is unique,” said Professor Joachim Hauber, head of the antiviral strategy section at partner research institute, Hamburg’s Heinrich Pette Institute.

This approach is the only one that destroys HIV while leaving the previously infected cells virtually unharmed. They did this not only in the controlled environment of a Petri dish, where everything is standardized, but in living mice, where the reality is much more complex and unpredictable. But moving from mice to humans is an equally challenging step.

Dresden team leader Professor Frank Buchholz said the ‘molecular scissors’ which cut the virus could be used in ten years in humans, but unfortunately, his team doesn’t have the funding to continue the studies.

“Blood would be taken from patients and the stem cells which can form blood cells, removed,” he said.

Cutting viruses

What they do is extract white blood cells, give them a new gene, then reinsert them into the body. The body then naturally proliferates the cells, and the gene, throughout the whole body.

The theory was that the genetically altered immune cells would reproduce, cut the HIV from infected cells and leave them unharmed – and exactly this was observed in mice.

“The amount of virus was clearly reduced, and even no longer to be found in the blood,” said Hauber.

The researchers have managed to manipulate the enzyme so that it can identify a particular sequence and remove it, and they claim this can be applied successfully to over 90 percent of all HIV cases. Hopefully, they will receive the necessary funding, otherwise this is all in vain.

Via TheLocal.de