Saturday, June 3, 2023

Is There A Vaccine To Prevent Hiv

Prepvacc Phase 2b Trial

Why An HIV Vaccine

Finally, the PrepVacc is another multicentre, randomised, controlled, double-blind phase 2b vaccine study currently underway in Mozambique, South Africa, Tanzania, and Uganda. The study seeks to evaluate the effectiveness/efficacy of a combination of two HIV vaccine regimens with PrEP . The study commenced in January 2020 and is projected to complete in March 2023. A total of 1668 healthy HIV-uninfected adults are expected to be enrolled in the study and an equal number will be randomised into one of six groups to receive either the vaccine regime or placebo with PrEP. The primary endpoints will include evaluation of HIV infection in vaccine recipients and assessment of AEs associated with receiving either vaccine or PrEP regimes which may lead to the regimes being terminated. The ultimate goal is to determine if the vaccine leads to a decrease in HIV prevalence with adequate public health significance to justify implementation of the combination vaccine regimen . A complete list of ongoing vaccine trials is illustrated in Table 2.

Table 2 Illustration of ongoing HIV vaccine trials.

Vaccine Testing And Clinical Trials

First, HIV vaccines are tested in labs and animals. Then, a single HIV vaccine could take years of testing in humans before it would be OK for the public.

A vaccine to prevent HIV typically goes through three phases of clinical trials to test its safety and effectiveness. People in all three phases are supposed to keep practicing safe sex. They’re not deliberately exposed to HIV after they’ve been vaccinated.

Each phase must go well in order to move on to the next one.

  • Phase I lasts between 12 and 18 months. Small numbers of healthy, HIV-negative volunteers help researchers test the safety and figure out best doses.
  • Phase II can last up to 2 years. Hundreds of healthy, HIV-negative volunteers help researchers to refine dosing and test how well the immune system responds.
  • Phase III can last 3 to 4 years with thousands of healthy, HIV-negative volunteers.

Hiv Vaccines Based On The Induction Of Neutralizing Antibodies

Initially, scientists believed that neutralizing antibodies would be adequate to protect against HIV infection and many of the HIV vaccines in this category were designed to primarily target the envelope glycoproteins, gp120 or gp160 . The first experimental immunization of humans against HIV/AIDS was done in Zaire by Zagury and colleagues in 1986 . A small group of Zairians were vaccinated with a vaccinia vector expressing gp160, an envelope glycoprotein. The purpose of the study was to assess whether vaccination could induce neutralizing antibodies and cytotoxic T lymphocyte responses in HIV negative individuals. Administration of the recombinant vaccinia virus vaccine by scarification elicited weak humoral and cellular immune responses that were boosted by four additional immunizations to achieve anamnestic humoral responses and cellular responses, which persisted for more than a year . Following this pioneering in human experimental HIV/AIDS vaccine trial, over 250 clinical trials have been carried out, with the majority being early-phase trials . Approximately 140 of these trials were conducted in the United States with several others being carried out in African countries and Thailand . Major vaccine trials have been completed and timelines are shown in Table 1.

Table 1 Illustration of completed and documented HIV vaccine trials.

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Death From Yellow Fever

“I believe that I am on the trail of the true pathogen,” wrote the American physician Jesse Lazear on September 8, 1900, in a letter to his wife. Lazear researched malaria and yellow fever. He confirmed that the latter is transmitted by mosquitoes. To study the disease, he intentionally allowed himself to be stung, fell ill and died 17 days after writing the letter. Lazear was only 34 years old.

Researchers and their self-experiments

Hvtn 706/hpx3002/mosaico Phase 3 Efficacy Trial


Another mosaic-based vaccine concept currently in clinical trials is the HVTN 706/HPX3002 , or Mosaico trail. This multicentre, randomized, controlled, double-blind phase 3 efficacy trial is currently underway in Europe, North America, and South America. It commenced in October 2019 and is expected to be completed by September 2023. This study seeks to assess the safety and efficacy of the Ad26.Mos4.HIV and adjuvanted clade C gp140 and Mosaic gp140 protein vaccine prime-boost vaccine regimen in healthy, HIV-uninfected MSM and transgender people. This study has enrolled approximately 3800 participants, aged 18-60 years, and randomly allocated to receive either the vaccine or placebo as outlined in the HVTN 705/HPX2008. The primary endpoint is to assess vaccine efficacy. Secondary endpoints are, to assess the number of participants with solicited and unsolicited local and systemic adverse events , medically-attended adverse events and SAEs, frequency and magnitude of HIV Env-specific humoral and cellular immune responses, antibody titers for Ad26, risky sexual behaviour, and Pre-Exposure Prophylaxis intake. Preliminary results reported at the International AIDS conference in Mexico city , showed evidence of vaccine induced immune responses to different HIV strains circulating worldwide .

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Hvtn 097 Phase 1b Vaccine Trial

The first vaccine concept tested by HVTN based on the RV144 concept was the HVTN 097 trial , which was a randomized, controlled, double-blind phase 1b study done in South Africa . The trial was designed to assess the safety and immunogenicity of the vaccine regimen in healthy, HIV-uninfected South African adults. The regimen consisted of two prime doses of the experimental canarypox HIV vaccine ALVAC-HIV followed by two booster shots of the AIDSVAX B/E. Study participants were randomized into three groups, in a 3:1:1 ratio, to receive the vaccine combined with tetanus and hepatitis B immunizations, the vaccine only or placebo. The tetanus and hepatitis B immunizations were included to assess possible cross-correlates of immune responses to HIV vaccine, however no significant differences in HIV immune responses were observed indicating that subsequent results were solely due to immune responses to HIV . The prime-boost vaccine regimen induced mostly Env-specific CD4+ T cell responses at significantly higher levels compared to RV144 vaccine recipients . IgG antibodies recognizing the V1V2 region and the IgG3 binding antibody responses to both gp120 and V1V2 antigens were also significantly higher among HVTN 097 vaccine recipients relative to RV144 recipients. ADCC antibody responses were also higher in HVTN 097 than in RV144, 72.6% and 58.5% , respectively. These favourable results provided compelling rationale for conducting larger clinical trials in South Africa .

Myth: An Hiv Vaccine Already Exists

Fact: This is also false. There is no licensed vaccine against HIV or AIDS, but scientists are getting closer than ever before to developing an effective vaccine against HIV. In 2009, a large-scale vaccine study conducted in Thailand showed that a vaccine combination could prevent about 32 percent of new infections. The HVTN is leading the effort to build on these results, and planning for several studies is underway.

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How Many Vaccinations Will A Person Need To Be Protected

The number of vaccinations needed for HIV protection can only be determined through clinical trials and will depend on the specific vaccine regimen being tested. The ultimate goal is to develop vaccines that require the fewest possible vaccinations. It is possible that first-generation HIV vaccines will require more vaccinations, and that improvements resulting from further research will allow for fewer vaccinations.

How Is A Preventive Hiv Vaccine Different From A Therapeutic Hiv Vaccine

Moderna develops vaccine for HIV/AIDS

While a preventive HIV vaccine is given to people who do not have HIV, a therapeutic HIV vaccine is given to people who already have HIV. The goal of a therapeutic HIV vaccine is to strengthen a persons immune response to the HIV that is already in the persons body. Researchers are exploring the use of therapeutic HIV vaccines:

  • To slow down the progression of HIV infection
  • To eliminate the need for antiretroviral therapy while keeping undetectable levels of HIV

To learn more, read the HIVinfo What is a Therapeutic HIV Vaccine? fact sheet.

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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.

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

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!

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Whats A Proof Of Principle

A proof of principle is a study that tests and confirms a hypothesis. This phase I study of IAVI G001 began in 2018 to test the hypothesis that a self-assembling nanoparticle of engineered HIV envelope proteins could activate naive B cells. And it worked.

What we did is show that the concept can work in humans, Schief said. We have a theory of how to design a vaccine that will elicit the response we want. We think the first shot must achieve a certain goal, to induce responses from these cells. And we showed it did. Proof of principle means you can do it again, starting from a different set of rare cells.

Schief cautioned that the study has not been peer reviewed, nor has a paper been written about the results, but he expects the review to happen sometime this summer.

How Is Prep Different From A Vaccine

Treatment programme cuts HIV transmission rate

Reasons PrEP may not be for you include:

  • Cost, since the medications can be expensive

  • Barriers to getting the needed medication

  • Needing to take the medication every day

  • Side effects

PrEP is also not 100% effective in preventing HIV. So, although PrEP would be an important preventative strategy, a vaccine would likely be a more accessible and impactful option overall.

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Broadly Neutralizing Antibodies And The Subsequent Antibody

Researchers have attempted to produce immunogens that induce the immune system to synthesize broadly neutralizing antibodies for several years. BNAbs inhibit the virions from entering the host cells, preventing HIV integration into the genome. Their role is particularly important because bNAbs are able to protect against the strain that the patient has been infected with as well as multiple different immunological strains . Though Env-specific bNAbs are produced in patients with chronic HIV-1 infections, an antibody must undergo extensive somatic mutation with possible insertions or deletions in the immunoglobin heavy and light chains in the germinal center. BNAbs also typically have a third heavy-chain complementarity-determining region loop, and this feature allows the antibody to combat the Env glycan shield. Some researchers tracked the evolution of the antibody to its development into a bNAb in an effort to understand the generation of bNAb . However, despite all the different versions of HIV envelope glycoproteins studied and synthesized, these glycoproteins or fragments have been unable to elicit a neutralizing response to primary isolates of HIV-1 .

Researchers assessed VRC01 further and found that it protected against HIV-1 clades B and C in vitro. Subsequently, they tested VRC01 in two simultaneous proof-of-concept trials, HVTN 703 and 704, starting in 2016. These trials were completed to learn whether this bnAb could prevent HIV-1 acquisition .

Major Scientific Hurdles In Hiv Vaccine Development: Historical Perspective And Future Directions

  • 1KwaZulu-Natal Research Institute for Tuberculosis and HIV , Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
  • 2Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA, United States

Following the discovery of HIV as a causative agent of AIDS, the expectation was to rapidly develop a vaccine but thirty years later, we still do not have a licensed vaccine. Progress has been hindered by the extensive genetic variability of HIV and our limited understanding of immune responses required to protect against HIV acquisition. Nonetheless, valuable knowledge accrued from numerous basic and translational science research studies and vaccine trials has provided insight into the structural biology of the virus, immunogen design and novel vaccine delivery systems that will likely constitute an effective vaccine. Furthermore, stakeholders now appreciate the daunting scientific challenges of developing an effective HIV vaccine, hence the increased advocacy for collaborative efforts among academic research scientists, governments, pharmaceutical industry, philanthropy, and regulatory entities. In this review, we highlight the history of HIV vaccine development efforts, highlighting major challenges and future directions.

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How Long Does Vaccine

HIV vaccine-induced seropositivity in HIV-negative vaccine recipients varies substantially depending on the specific vaccine used and the participant’s individual response to it. In trials conducted by the HIV Vaccine Trials Network over the last 10 years, the average chance of VISP occurring was about 42%.5 With a few vaccines, VISP has lasted for more than 15 years. For other vaccines, VISP did not occur at all. Because different types of diagnostic tests may be used, VISP can appear at any point after administration of a vaccine candidate, even after completion of the HIV vaccine study. Study volunteers in NIAID-sponsored trials are offered long-term monitoring to watch for VISP providers should encourage their patients to ask what long-term monitoring/testing is available from the trial sponsors.

5 Cooper, C. J., Metch, B., Dragavon, J., Coombs, R.W., Baden, L. R. . Vaccine-induced HIV seropositivity/reactivity in noninfected HIV vaccine recipients. JAMA, 304.

To Stop Hiv Researchers Are Investigating An Mrna Vaccine

Now proven with COVID, mRNA could lead to HIV vaccine
  • Researchers are using Modernas mRNA vaccine technology to target HIV.
  • The eventual goal is to stimulate the immune system to produce broadly neutralizing antibodies that target multiple HIV strains.
  • Over the past few decades, finding a safe and effective vaccine to prevent HIV infection has proven to be very challenging.

An early stage clinical trial of an mRNA-based HIV vaccine could begin this month, according to the U.S. National Library of Medicine clinical trial registry.

This vaccine candidate uses technology developed by biotech company Moderna the same technology used for its highly effective COVID-19 vaccine.

The trial, which builds on earlier research by the International AIDS Vaccine Initiative and Scripps Research, would test the first stage of a multistep vaccine regimen.

The eventual goal is to stimulate the immune system to produce broadly neutralizing antibodies that target multiple HIV strains.

Additional clinical trials will be needed before a vaccine capable of preventing HIV infection is available.

Many people are familiar with the coronavirus spike protein: mRNA vaccines train the immune system to produce antibodies that target the spike protein and prevent the virus from infecting cells.

HIV also has a spike-shaped virus protein known as Env, or the envelope protein. The shape of this protein varies among different strains of the virus, making it harder to target with antibodies.

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Vax003 And Vax004 Efficacy Trials

1994 saw the emergence of two possible vaccine candidates that were used in efficacy trials. These vaccine concepts were advanced to efficacy trials because they conferred protection to chimpanzees following HIV challenge and were safe and immunogenic in phase 1/2 clinical trials in humans . The first two efficacy trials were carried out, from 1998 to 2003, by VaxGen in North America and Thailand . Based on the knowledge gained regarding genetic variability of HIV strains and the ability to use various co-receptors, the two initial candidate HIV vaccines were redesigned as bivalent gp120 vaccines for the North American trial and for the Thailand trial . The two redesigned gp120 vaccines were derived from R5 and X4 strains . The VAX004 efficacy trial recruited 5417 volunteers who were mainly men who have sex with men in North America, and the VAX003 trial recruited 2545 volunteers comprising intravenous injection drug users in Bangkok, Thailand. Unfortunately, in 2003, data analysis revealed that the two vaccines did not prevent HIV acquisition and did not ameliorate disease .

Applying Mrna Vaccine Approach To Hiv

The International AIDS Vaccine Initiative and Scripps have partnered with Moderna to test an mRNA-based vaccine version of this approach.

Messenger RNA, or mRNA, contains a blueprint for making a specific protein. MRNA vaccines deliver these instructions to the cells, which then produce the protein.

In the phase 1 trial using Modernas technology, the mRNA vaccine will carry the instructions for a protein that stimulates the immune system in the same way as the earlier Scripps and International AIDS Vaccine Initiative trial.

This trial will enroll 56 healthy people without HIV, and will test two versions of the vaccine candidate.

Two groups of people will receive a mix of the two vaccine candidates, and the other two groups will receive one or the other.

Researchers will look to see whether the vaccine generates the desired immune response the immune precursors cells and whether there are any safety concerns.

This is only the first of several clinical trials, so it will take some time before scientists know whether this approach can prevent HIV infection.

However, many people will be watching closely to see whether the mRNA technology does for HIV what it did for COVID-19.

If nothing else, I hope that were able to leverage the lessons learned from the COVID-19 trials for developing a safe and effective HIV vaccine, said Anthony J. Santella, DrPH, a public health researcher at the University of New Haven.

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