By Michael Gwarisa
Over the past few years, several interventions have been developed as the world intensifies the fight against HIV and AIDS. These include combined strategies such as behavioral, biomedical, and surgical methods to prevent HIV like Voluntary Medical Male Circumcision (VMMC).
For other epidemics such as smallpox, polio, measles and COVID-19, vaccines saved the day as they proved to be efficient tools against the further spread of infections. However, for HIV, it has been a different story altogether. On May 18 every year, the world unites to commemorate World AIDS Vaccine Day in honour of Clinton’s speech that underlined the urgent need for an effective vaccine. World Aids Vaccine Day was observed for the first time in 1998. Although finding an effective HIV vaccine would significantly improve prevention strategies to control the AIDS pandemic, history has shown that getting an effective HIV vaccine has been an elusive target.
The search for an HIV vaccine has been going on for more than four decades, with the first HIV vaccine trials having been conducted in 1987. In Zimbabwe, the first HIV vaccine trials were conducted from 2016. The University of Zimbabwe Clinical Trials Research Centre (UZ-CTRC) banner, has participated in at least five past HIV vaccine trials since 2016. These include the HVTN 703/HPTN 081/AMP Study where 430 participants were enrolled between 2016-2021, and the Imbokodo HIV vaccine studies amongst other trials.
The HVTN 705/HPX2008 or Imbokodo study, which began in 2017 to test whether the Imbokodo vaccine regimen could prevent women in Sub-Saharan Africa from getting HIV was discontinued in 2021 following indications that the vaccine did not provide sufficient protection against infection. Even though this development frustrated hopes of getting an effective HIV vaccine in our lifetime, findings from both clinical and pre-clinical studies have provided a new roadmap to inform future vaccine design.
Dr Muchaneta Bhondai-Mhuri, Investigator of Record at University of Zimbabwe Clinical Trials Research Centre told a Media and Science Café on HIV Vaccine Research that there was promising evidence that could lead to the development of an HIV vaccine in the future.
We will not give up hope for looking for an HIV vaccine,” said Dr Bhondai-Mhuri.
“With every HIV vaccine study that is being done, we are learning something new. Even if the vaccine does not show us that it is efficacious, we learn something new. For example the HVTN 705 study, did show us that even though it was not efficacious, participants can mount an immune response. So that is new information that will lead to the development of an HIV vaccine.”
Lessons from the Imbokodo or HVTN 705 study
The primary purpose of HVTN705 study was to assess the preventive vaccine efficacy (VE), safety and tolerability of a candidate HIV vaccine (HIV) infection in HIV-seronegative women residing in sub-Saharan Africa. The vaccine showed no safety concerns even though it did not provide sufficient protection against HIV infection, according to a primary analysis of the study data. Under the study, participants mounted an immune response leading to Vaccine-Induced Seropositivity(VISP).
“The purpose of this study was to assess the preventive vaccine efficacy, the safety and the tolerability of a candidate HIV vaccine for infection in HIV seronegative women who were residing in sub-Saharan Africa. So we wanted to see, one, was this vaccine safe? Two, we wanted to see if it can be tolerated. We wanted to see if it was effective in the prevention of HIV,” said Dr Bhondai-Mhuri.
The UZ-CTRC also participated in the monumental proof-of-concept Antibody Mediated Prevention(AMP) studies. The AMP studies demonstrated that a broadly neutralizing antibody (bnAb) called VRC01 was effective at preventing the acquisition of HIV strains that were sensitive to the Bnab. However, VRC01 did not significantly reduce overall HIV acquisition in the AMP trials . Investigators found that only 30% of the HIV strains circulating in the regions where the trials were conducted were sensitive to VRC01. By this, the vaccine trials showed that there are different sub-types of HIV. There are some sub-types which were shown to respond to this antibody, but not all of them.
“Therefore, overall, it did not reduce the overall risk of acquiring HIV, but it gave us hope because it taught us that people can receive monoclonal antibodies intravenously without feeling too uncomfortable. So it showed that it was possible and it is safe for people to receive monoclonal antibodies.”
The results also proved that the concept is acceptable in African communities, as shown by the number of people who participated in this study. Over 430 participants participated and continued in the study until 2021. The results from the AMP trials were instrumental in the development of future research on bnAbs.
“It paved the way for the development of more potent broadly neutralizing antibodies (BNABs), so the information it gave us and everything we learned from this study paved the way for the development of better monoclonal antibodies. It also showed us that there was a need to use combination monoclonal antibodies to be able to achieve effectiveness in the prevention of HIV.”
Why an HIV Vaccine Is Important?
She added ‘An HIV vaccine would address some of the challenges associated with HIV prevention and treatment such as drug adherence, and access to medications among other issues. Vaccines typically provide long-lasting protection and can be given broadly to a wide range of people, leading to community immunity. In the event that an effective vaccine is developed, vaccines could eliminate adherence and stigma problems associated with HIV treatment and could be cost-effective when compared with a lifetime of treatment. It’s also because key populations including people who inject drugs, sex workers, and adolescent girls and young women, who account for nearly half of all new infections — are less likely to access existing treatment and prevention services, We need to ensure that HIV prevention tools are accessible to those most in need. We also need new ways to stop the spread of HIV.’
“We know that more than 20 percent of people in the world living with HIV experience problems with accessing HIV treatment. We also know that all HIV prevention modalities have their challenges including adherence and access. We know that a vaccine can be present in someone’s immune system for a very long time so it entails long-term prevention.”
‘HIV vaccine research benefits the HIV prevention and treatment field broadly as it has made fundamental contributions to scientists’ understanding of the biology of HIV infection, including the human immune response to infection.’
“Vaccine-focused research into HIV-blocking antibodies has resulted in those antibodies being investigated as stand-alone prevention products. Beyond HIV/AIDS, the investment in HIV vaccine research capacity has strengthened health systems and HIV vaccine research has contributed to medical advances for other diseases, leading to longer, healthier lives for people all over the world,” said Dr Bhondai-Mhuri.
Lessons Learnt from Past Vaccine Trails
Several lessons can be drawn from the vaccine trials. According to Dr Bhondai-Mhuri, the Imbokodo study showed that there were no safety concerns with giving the vaccine even though it did not provide sufficient protection against HIV infection.
“According to the primary analysis of the study data, participants mounted an immune response leading to what is called vaccine-induced seropositivity. This is a good sign because it shows us that individuals can develop active immunity against HIV if they are given a vaccine. In as much as we did not see efficacy, we can see that the road is now open to develop more efficacious candidates because people can develop an active immune system which means there is a possibility that if you get a good vaccine people can start to make their antibodies to fight HIV.
“This also means that someone now has circulating antibodies against HIV, if they test for HIV using the standard test which we use at the moment, which is the antibody-based test, they will test false-positive even though they do not have the HIV antigen in their body. What it means is that this person who’s been exposed to this vaccine, when they need to have an HIV test done, we need to test for the antigen rather than testing for the antibody. Therefore they are continuing to be tested at our study sites for as long as they need HIV testing, they’ll be tested at our sites using both an antibody-based test and an antigen-based test until such a point when they are now negative based on the antibody test.
“So yes it might seem like it’s a bad thing that people are developing VISP, but there is no way around it. If someone has to develop an active immunity against HIV based on them having received a vaccine they have to build the VISP or Vaccine Induced Seropositivity. This is a positive sign. It shows us that there is a need to improve the vaccines to make them more effective and in the future, this could change the face of HIV testing as more and more people become exposed to HIV vaccines.
“We’ve seen in Zimbabwe already we have quite many people who participated in HIV vaccines but as more and more people are exposed to HIV vaccines if they are proving that they are developingVISP, it means that we need to change our HIV testing for people who are vaccine-exposed from antibody-based testing to antigen-based testing.”
The Future of HIV Vaccine Research in Zimbabwe
There are multiple HIV Vaccine Trials ongoing worldwide and in Zimbabwe, the UZ-CTRC is part of the BRILLIANT Consortium holding out hope for the development and testing of HIV vaccine candidates in Africa.
“Multiple HIV trials are going on worldwide and these include combination broadly neutralizing antibodies. I think we’ve already talked about neutralizing antibodies and we said that the trials we’ve done, mostly the AMP-study, have shown us that it can work, it has shown that it is safe, it has shown us that it can be effective. So now we need more broadly neutralizing antibody trials. Att the moment, a couple of HIV vaccines are in trial, , including improvement of old candidates and development of new candidates’.
‘At UZ-CTRC, we recently completed participating in the multicentre, multicountro HVTN 140 study which was testing 3 broadly neutralizing monoclonal antibodies,” added Dr Bhondai-Mhuri.
She however said they were looking to get new trials, especially for broadly neutralizing antibodies and also for HIV vaccines through our other HVTN network, which is the HIV vaccine trials network, and the HPTN network.
Financing HIV Vaccine Research in Zimbabwe
Funding is the cornerstone of every research and gladly for the HIV Vaccine research, the United States Agency for International Development (USAID) has come through in a big way. In Zimbabwe, the University of Zimbabwe and regional partners were in 2023 issued a U.S. Agency for International Development (USAID) award of over US $45 million to implement the HIV Vaccine Innovation, Science, and Technology Acceleration in Africa (HIV-VISTA) program.
“I can say yes HIV vaccine trials are ongoing, yes we are participating and we are looking forward to participating in more and this includes with the partners that we’ve been working with and also with new research partners in the development of new candidates. We are happy that we are securing funding for African researchers to be able to develop a vaccine, to conduct preclinical trials and to conduct clinical trials. ,” said Dr Bhondai-Mhuri.
Although some highly effective HIV prevention tools are available, the epidemic continues. Hence the need for an effective HIV vaccine that the world could count on. An HIV Vaccine in our lifetime could greatly transform the HIV trajectory
