Thursday, December 8, 2022

Why No Vaccine For Hiv

Myth: The Search For An Hiv Vaccine Has Been Going On For A Long Time And It Just Isnt Possible To Find One That Works

With rapid development of COVID-19 vaccine, why no vaccine yet for HIV?

Fact: The science of HIV-vaccine development is challenging, but scientific understanding continues to improve all the time. In just the past few years there have been promising results from the RV144 study in Thailand as well as exciting laboratory work, such as the discovery of new broadly neutralizing antibodies against HIV. HIV is a powerful opponent, but scientists are constantly learning from one another and using advanced technology to fight it. Science has come a long way in the 30 years since AIDS was discovered. In comparing preventive HIV vaccine work to other vaccine development, the time it has taken is not so surprising it took 47 years to develop the polio vaccine!

How Many Hiv Vaccines Are In Clinical Trials

There is currently a vast research network related to HIV trials. There are over 700 trials related to HIV vaccines alone. These trials are in different stages of their research. About 50 studies are just beginning and looking for study volunteers. Others have finished collecting data and are looking into their results. Many studies have already been published.

The first study to show promise in preventing HIV was the RV-144 study in Thailand. While this vaccine candidate did show some benefit, it was only 31% effective in lowering HIV infection.

The HVTN 702 study took the lessons learned from the earlier RV-144 study in hopes of making a more effective vaccine. However, an interim analysis in early 2020 showed that the vaccine was not effective at preventing HIV. Study participants will continue to be followed, but no additional shots will be given.

There are also two large international studies that show promise. Both of them use mosaic vaccines vaccines that contain components from many HIV strains to trigger an immune response against several common HIV types.

The first study, called Imbokodo, uses a mosaic vaccine meant to prevent HIV infection in adult women. Participants in the study get the vaccine 4 times over 1 year. The study is currently in progress, and we can expect to see results this year.

About This Research Topic

Despite continuous progress in the development of anti-viral and anti-bacterial/parasite drugs, the high cost of medicines and the potential for re-infection, especially in high risk groups, suggest that protective vaccines to some of the most dangerous persistent infections are still highly desirable. There …

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Myth: Since Pills Can Prevent Hiv Infection An Hiv Vaccine Is No Longer Necessary

Fact: HIV-negative people who are at risk can take antiretroviral medication daily to lower their chances of becoming infected if they are exposed to the virus. The pill Truvada has been approved by the US Food and Drug Administration for use by people who are sexually active with multiple partners, for people who do not use condoms or do not use them all the time, and for people who have an HIV-positive partner or partners whose HIV status is unknown. PrEP is unlikely to be an option for everyone because the pills are expensive, may cause side effects, and may not be accessible. Remembering to take a pill every day is also challenging for some people. PrEP is an important new addition to the existing methods of HIV prevention, however, the most effective way to eliminate a disease is by using an effective vaccine. Vaccines are an effective, affordable and practical option. Until we have an effective vaccine, the HVTN supports the use of all available HIV prevention tools and encourages people to learn about their prevention options.

Still No Vaccine For Hiv

HIV/AIDS vaccine: Why don

Before diving into the challenges with vaccines, heres a reminder on how they work: Vaccines deliver a small and modified amount of a particular virus to your immune system. This tiny introduction isnt enough to make you sick instead, it lets your body recognize the particles and build up a tailored defense to those molecules. The next time around, when you actually get exposed to the virus, then that virus will trigger your immune cells to wake up, says Wilton Williams, an assistant professor at the Duke University School of Medicine.

HIV is particularly good at tricking immune systems, says Williams, who is working to develop an HIV vaccine. As soon as the virus starts replicating in our bodies, molecules on its surface which our immune system reads to determine whether a cell is friend or foe look a lot like other proteins in healthy people. The resemblance allows the virus to get a big head start on infecting cells, Williams says, before the immune system recognizes a threat.

Any preventive measure that convinces the immune system to attack this protein in HIV must be fine-tuned. The vaccine will likely deliver tweaked versions of HIV surface proteins. These molecules must be distinct enough from actual HIV for the immune system to recognize them as a threat while also provoking the exact infection-fighting qualities needed to fend off a real infection.Other viruses dont require vaccine developers to engineer this kind of deception.

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Off Treatment And Still Undetectable

One approach to curing HIV is called treatment-free remission, or ART-free remission. This approach is also called a functional cure, because it would render HIV harmless without eliminating HIV from the body completely.

ART does a great job at eliminating HIV from the circulating blood of a PLWH, which is what keeps those on ART healthy and makes it impossible for those who are virally suppressed for at least six months to transmit HIV to their sexual partners . But even with viral suppression by ART, HIV remains hidden in a so-called HIV reservoir made up of immune system cells that contain HIV in the form of HIV DNA . Such HIV is called latent, because it hides from detection by the immune systemand these cells are called resting, because they are not actively producing new copies of the virus.

When latently infected, resting immune cells are reactivated, they begin to churn out new copies of fully active HIV. This explains why PLWH need to remain on ART throughout their entire lifeif ART stops, detectable virus comes back.

Finding ways to prevent the latent reservoir from becoming productive after stopping ART is thus a major focus of research into a cure for HIV today. This kind of sustained ART-free remission, sometimes called a functional cure, would allow a PLWH to keep latent virus suppressed without daily medication. Researchers are investigating a number of different strategies for achieving ART-free remission of HIV.

Kicking And Killing Latent Hiv

One of the greatest obstacles to developing an HIV vaccine is the speed by which the virus is able to established latent reservoirs to evade immune detection. It is believed that this can happen as quickly as four hours in case of anal sex transmissionmoving quickly from the site of infection to the lymph nodesto up to four days in other types of sexual or non-sexual transmission.

To date, were neither entirely sure how extensive or large these reservoirs may be nor their potential to cause viral rebound in those believed cleared of infection.

Some of the most aggressive facets of research involve a so-called “kick-kill” strategy, using stimulating agents that can “kick” latent HIV out of hiding, thereby allowing a secondary agent or strategy to “kill” the newly exposed virus.

In this regard, scientists have had some success using drugs called HDAC inhibitors, which have been traditionally used to treat epilepsy and mood disorders. While studies have shown that newer HDAC drugs are capable of “waking” a dormant virus, none have yet been able to clear the reservoirs or even reduce their size. Hopes are currently being pinned on the combined use of HDAC and other novel drug agents .

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Diagnosis And Treatment Of Aids

Presence of HIV in the body can be detected through various blood tests. Antibody/antigen tests help detect the virus within 18 45 to days of the transmission and Antibody tests can detect the same within 23 90. The most advanced test used is Nucleic acid test . It is capable of detecting the virus in the earliest stages, that is, within 5 to 21 days of the transmission.Unfortunately, there is no cure for AIDS. However, if detected early, the progress of HIV infection can be slowed down through antiretroviral therapy.

How Hiv Hampers Vaccine Development

Why Is It So Difficult To Develop an HIV Vaccine?

From the most fundamental standpoint, efforts to develop an HIV vaccine have been hampered by the genetic diversity of the virus itself. The replication cycle of HIV is not only fast but is prone to frequent errors, churning out mutated copies of itself which recombine into new strains as the virus is passed from person to person. Developing a single vaccine able to eradicate over 60 dominants strains as well as the multitude of recombinant strainsand on a global levelbecomes all the more challenging when conventional vaccines can only protect against a limited number of viral strains.

Secondly, fighting HIV demands a robust response from the immune system, and this again where systems fail. Traditionally, specialized white blood cells called CD4 T-cells initiate the response by signaling killer cells to the site of the infection. Ironically, these are the very cells that HIV targets for infection. By doing so, HIV hobbles the bodys ability to defend itself as the CD4 population is systematically depleted, resulting in the eventual breakdown of defenses called immune exhaustion.

Finally, the eradication of HIV is thwarted by the virus ability to hide from the bodys immune defenses. Soon after infection, while other HIV is circulating freely in the bloodstream, a subset of virus embeds itself in hidden cellular sanctuaries . Once inside these cells, HIV is shielded from detection.

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Induce And Reduce: Our Approach To Hiv Cure

HIV is a sneaky virus that can persist in a small population of cells even while its spread to new cells is being suppressed by ARVs. Unless we can find a way to expose hidden HIV and selectively target these cells, well continue to require chronic treatments to keep the virus at bay. Thats why cure research currently underway by Qura Therapeutics and ViiV Healthcare targets these pockets of virus through the concept of induce and reduce.

This strategy is first focused on driving HIV hidden in human immune cells to make viral proteins that allow the cells with HIV to be recognised . Once cells harbouring HIV are exposed, drugs can then tag these reservoir cells for elimination by the host immune system . The Induce and Reduce agents will all be given while people are on suppressive ARV therapy to protect healthy cells from the virus. While it may sound straight forward, it has been a major challenge to reactivate the virus in animals or people in an effective and safe way.

The research required to develop an HIV cure is complex and requires a commitment to the long-term. As we look ahead to the future, were optimistic that the initial steps weve taken towards establishing our approach to HIV cure will move from the laboratory into clinical studies in people, big steps in the long journey to finding a cure for HIV. It is our lifes work to end the HIV epidemic, and we will be here until HIV isnt.

Reference

Where Do Things Stand Now

Efforts to develop a vaccine have been going on for decades but have so far all ended in failure.

Last year, a study called Uhambo that was taking place in South Africa and involved the only vaccine candidate ever shown to provide some protection against the virus frustratingly ended in failure.

J& J’s vaccine candidate is currently being trialed in 2,600 women in sub-Saharan Africa in the Imbokodo trial, which is expected to report results in the coming months.

It’s also being tested in around 3,800 men who have sex with men and transgender individuals across the U.S., South America and Europe in the Mosaico trial.

The J& J vaccine uses similar adenovirus technology to its COVID-19 vaccine, in other words, a genetically modified cold virus delivers genetic cargo-carrying instructions for the host to develop “mosaic immunogens,” which are molecules capable of inducing an immune response to a wide variety of HIV strains.

This is followed up by directly injecting synthetic proteins in later doses.

Another promising approach is to try to generate “broadly neutralizing antibodies” which bind to areas of the HIV virus that are common across its many variants.

The International AIDS Vaccine Initiative and Scripps Research recently announced results from an early-stage trial showing their mRNA vaccine candidate, developed with Moderna, stimulated the production of rare immune cells that create bnAbs.

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Why Is It So Challenging

Vaccines against COVID-19 were developed in record time and have shown remarkable levels of safety and efficacy, helping drive down caseloads in the countries fortunate enough to have wide access.

Many of these shots were developed using technologies that were previously being tried out on HIV so why have we not had breakthroughs yet?

“The human immune system doesn’t self-cure HIV, whereas what was very clear was the human immune system was quite capable of self-curing COVID-19,” Larry Corey, principal investigator of HVTN, a global organization funding HIV vaccine development, told AFP.

COVID vaccines work by eliciting antibodies that bind to the virus’ spike protein and stop it from infecting human cells.

HIV also has spike-shaped proteins on its surface, which are the target of HIV vaccine development.

But while COVID has a number of well-known variants circulating worldwide, HIV has hundreds or thousands of variants inside each infected person, William Schief, an immunologist leading the development of an mRNA HIV vaccine at Scripps Research Institute told AFP.

Because it’s a “retrovirus” it quickly incorporates itself into its host’s DNA. An effective vaccine will need to stop the infection dead in its tracks, not just reduce the amount of virus and leave the remainder to stay with the person forever.

Hunting The Holy Grail: The Marred History Of Hiv Vaccine Trials

Immunology and the Quest for an HIV Vaccine: A New ...

With the recent news that Moderna is set to start human trials of its mRNA HIV vaccine, CTA charts the history of past attempts.

According to the International AIDS Vaccine Initiative , there were 38 million people living with HIV/AIDS in 2020, with 1.5 million contracting the virus that year. 27% of people living with the virus dont have access to treatment, representing a tremendous unmet need and a huge transmission risk.

The search for an HIV vaccine began soon after scientists isolated the virus and confirmed that it caused AIDS in 1984. The scientific community assumed that developing a vaccine for the virus would be fairly simple and would be achieved within a few years, but that was almost 40 years ago and still, no pharma company or research team has come anywhere close to finding one.

HIV has proven to be a tough enemy to defeat due to its ever-changing and evolving structure. Despite no longer being a death sentence thanks to life-saving antiretroviral treatments that dramatically reduce viral load, a vaccine for the highly stigmatised disease is considered the holy grail in stopping HIV, but a true prophylactic agent has remained elusive.

In the last few decades, science has made great strides in understanding the viruss complex structure.

Here, Clinical Trials Arena charts the breakthroughs and failures of HIV vaccine development of the last three decades and profiles the new hopes of recent years.

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Moderna To Begin Human Trials For Two Experimental Hiv Vaccines

The vaccines are mRNA based, like the biotech companys Covid-19 vaccine

Daily Correspondent

The pharmaceutical and biotech company Moderna could begin human clinical trials for two new mRNA-based HIV vaccines as early as September 19, according to a study record posted to the United States National Institutes of Health Clinical Trial registry.

The vaccines will use a mechanism similar to the ground-breaking mRNA system in their Covid-19 vaccine, reports Science Alerts Fiona Macdonald. The study is expected to take place until May 2023.

For several years, scientists have been researching the effectiveness and potential of mRNA vaccines for cancer treatments and other diseases in animal models. The Pfizer-BioNTech and Moderna Covid-19 vaccines were the first mRNA vaccines used in humans. The mRNA vaccines work by giving cells instructions to make bits of the same proteins on a viruss outer shell. The proteins then prime immune cells to recognize and destroy the virus, reports Sarah Chodosh for Popular Science.

Creating a vaccine that targets HIV is challenging because the retrovirus become part of the human genome 72 hours after transmission. To prevent infection, high levels of neutralizing antibodies must be present at the time of transmission, per Popular Science.

We Should Applaud These Groundbreaking Discoveries But Were Not At The Finish Line Yet

This is why the Global Fund, the organization that receives 100% of money generated by partners, is so important. While the medical community continues to work on finding a safe, cost-effective cure for HIV/AIDS, Global Fund programs in over 100 countries are focused on scaling up access to daily antiretroviral medicationthe current, closest thing to a cure for people living with HIV. These programs also provide prevention services, care, treatment and education to the people most affected by HIV, which are crucial to limiting the spread of the virus.

Given the devastating impact of the current COVID-19 pandemic on the fight to end AIDS, supporting the Global Fund is more crucial now than ever before. Join and help ensure those living with HIV can continue to access essential programs and services.

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