HIV vaccine trial hits snag

Finding a vaccine for HIV prevention, which cost the government Shs61b, has been one of the biggest interests of scientists, a move that health experts and civil society organisations (CSOs) say when successful, would play a very significant role in attaining the goal of ending Aids by 2030.

Uganda registers around 52,000 new HIV infections annually, according to information from the Uganda Aids Commission.

The PrEPVacc HIV prevention study is for experimental HIV vaccine regimens and a new form of oral pre-exposure prophylaxis (PrEP) which were being trialled in Uganda, Tanzania and South Africa.

The oral PrEP arm has been allowed to continue to the completion date of the project which was planned to run from 2018 to 2024.

Dr Eugene Ruzagira, the PrEPVacc’s Trial Director, who is based at the Medical Research Council / Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI & LSHTM) Uganda Research Unit, said in a statement on Wednesday that the vaccine trial has stopped prematurely. 

“Vaccinations to PrEPVacc trial participants have been stopped because an analysis of the data collected so far by our Independent Data Monitoring Committee has led them to conclude that there is little or no chance of demonstrating that the vaccines we are testing are reducing the risk of acquiring HIV,” he said.

By the time the vaccine arm was stopped, 1,512 volunteer participants had enrolled. At enrolment, the study leaders said, participants reported behaviours that made them more vulnerable to acquiring HIV.

Prof Pontiano Kaleebu, the trial’s chief investigator, told this newspaper last evening: “Some may be discouraged, others may be encouraged. For others, it might be an impetus to say ‘We have to do better’ and go back to the drawing board.”

Prof Kaleebu is the Uganda Virus Research Institute director.

“The biggest challenge with HIV is to get that design [of a vaccine] that will induce the right antibodies. And which antibodies are those? It is not easy [to find] because even nature is failing to completely eradicate this,” he added.

Dr Fred Collins Semitala, the executive director of Makerere University Joint Aids Programme, on the other hand, said the HIV vaccine world has been an area which is a bit “turbulent.”

“It has not been very easy to identify something potent and safe for widespread scale-up. As scientists, it was one of the avenues they were checking on but I think there should be more in the pipeline,” he told this newspaper.

“It is disappointing that something has not worked but it doesn’t stop people from being innovative and creative. Even then, there are some lessons [that have been learnt],” he added.

PrEPVacc is led by African researchers from Entebbe in Uganda at the MRC/UVRI and LSHTM Uganda Research Unit. Records on the PrEPVacc website indicate there are 80 senior scientists, clinicians, social scientists, community liaison specialists and professional support roles, from 15 partner organisations.

The trial had two experimental combination vaccine regimens that researchers wanted to see whether they could provide any protection against HIV in populations at risk of acquiring HIV. 

“Both [vaccine regimens] have already been evaluated in clinical trials in the US, Europe and Africa and have demonstrated their safety and ability to induce immune responses. The outcome of PrEPVacc will tell us whether the regimens can protect against HIV infection,” the information from the PrEPVacc website reads.

Before the actual trial where vaccines were administered, preparations were done. Preparations for the trial included an observational study, whose first participants were enrolled in July 2018. The first participants in the clinical trial enrolled in December 2020 and by March 2023, a total of 1,512 had been enrolled.

The trial relied on funding from Europe and partner institutions in the study. “The European and Developing Countries Clinical Trials Partnership (EDCTP) awarded a grant of €15 million (Shs61 billion) for the study and all of the institutional partners are providing co-funding through staff salaries,” more information from the PrEPVacc website reads.

Following the announcement of the stopping of the trial on Wednesday, many people and organisations including the International Aids Society (IAS) came up to call for increased efforts in the search for an HIV vaccine.

“We cannot and will not lose hope that the world will have an effective HIV vaccine that is accessible by all who need it, anywhere,” IAS executive director Birgit Poniatowski said in a statement: “A vaccine remains one of our most powerful tools to reach and change the lives of vulnerable communities and key populations in the most affected parts of the world.”

In Prof Kaleebu’s words

“The first PrEPVacc trial participants in Masaka are helping their communities, and the world, by answering important questions about how we can best prevent HIV in future. These volunteers are critical to the success of PrEPVacc, but we would not be in a position to ask these questions without the efforts of many other participants and researchers in the past. PrEPVacc builds on a long history of partnerships between African countries and European institutions, including EuroVacc, AfrEVacc, TaMoVac and MDP. I have been working at Imperial College London on ways to prevent HIV since the virus was first discovered and I am immensely proud that we now have this African-led, European-supported trial beginning in Uganda.”

Prof Pontiano Kaleebu, the UVRI director who is the trial’s chief investigator in a statement on December 16, 2020 when vaccinations (actual trial) started in Uganda, said:

‘‘The development of a vaccine preventing HIV is a critical goal for Africa. It is a goal that must have even greater urgency now that no HIV vaccines are being trialled for efficacy anywhere in the world. We have come so far in our HIV prevention journey, but we must look to a new generation of vaccine approaches and technology to take us forward again. We must also look to a new generation of leaders. We set up PrEPVacc to grow our capacity in Africa to do future trials ourselves and to develop those who will lead them here in Africa. Our participants and collaborators should be very proud that PrEPVacc is the largest HIV vaccine efficacy trial to run in East Africa.”

Prof Pontiano Kaleebu, the UVRI director who is the trial’s chief investigator in a statement on December 6, 2023 after the trial was stopped, said:

‘‘The development of a vaccine preventing HIV is a critical goal for Africa. It is a goal that must have even greater urgency now that no HIV vaccines are being trialled for efficacy anywhere in the world. We have come so far in our HIV prevention journey, but we must look to a new generation of vaccine approaches and technology to take us forward again. We must also look to a new generation of leaders. We set up PrEPVacc to grow our capacity in Africa to do future trials ourselves and to develop those who will lead them here in Africa. Our participants and collaborators should be very proud that PrEPVacc is the largest HIV vaccine efficacy trial to run in East Africa.”

HIV VACCINE SEARCH JOURNEY THAT HAS ENDED IN HEARTBREAK

In December 2020,  hopes were high when the first participants in the clinical trial for experimental HIV prevention vaccine regimens enrolled.

Before the actual administering of the vaccine regimens started in 2020, preparations had been done since 2018. Preparation for the trial included an observational study, whose first participants were enrolled in July 2018. The first participants in the clinical trial enrolled in December 2020 and by March 2023, a total of 1,512 had been enrolled.

The trial was running in Uganda (specifically in Masaka), Tanzania and South Africa under the PrEPVacc project which was planned to run from January 2018 to December 2024. The trial had two arms, the other arm had a new form of oral pre-exposure prophylaxis (PrEP) which the researchers were testing. 

PrEPVacc is led by African researchers from Entebbe in Uganda at the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine (MRC/UVRI and LSHTM) Uganda Research Unit.

The vaccine regimens have already been evaluated in clinical trials in [the] United States, Europe and Africa and have demonstrated their safety and ability to induce immune responses, according to information from the PrEPVacc website. The outcome of PrEPVacc would tell scientists whether the regimens can protect against HIV infection.

The trial relied on funding from Europe and partner institutions in the study. The European and Developing Countries Clinical Trials Partnership (EDCTP) awarded a grant of €15 million (Shs61billion) for the study and all of the institutional partners are providing co-funding through staff salaries, more information from PrEPVacc website reads.

However, Dr Eugene Ruzagira, the PrEPVacc’s Trial Director, who is based at the MRC/UVRI & LSHTM Uganda Research Unit in Uganda, said in a statement on Wednesday that the trial has stopped prematurely because of unconvincing data on their ability to protect vaccine recipients. However, the oral PREP arm would continue to the completion date.

Dr Ruzagira said this action followed an analysis of the data collected by their Independent Data Monitoring Committee which led “them to conclude that there is little or no chance of demonstrating that the vaccines we are testing are reducing the risk of acquiring HIV.

WHERE DO WE GO FROM HERE?

The Uganda Virus Research Institute (UVRI) director, Prof Pontiano Kaleebu, has said there are more HIV vaccine candidates in the pipeline in addition to ongoing studies aimed at discovering a vaccine that works. 

Prof Kaleebu is the chief investigator of the trial of the experimental HIV prevention vaccine regimens, which has been halted over the ineffectiveness of the regimens in preventing infection. The UVRI director also said there is a lot of work going on at UVRI to study HIV so that the right vaccine can be found in collaboration with scientists around the world.

“Globally, they [HIV vaccine candidates] are many but they are early stages. Some are being tested on animals or are at phase one [clinical trial], especially those germline-targeting vaccines and Ribonucleic acid (RNA) [vaccines],” he told this newspaper.

Germline-targeting vaccine design, according to available scientific information, is a new approach which centers on producing vaccines that stimulate the immune system to produce broadly neutralising antibodies (bnAbs) against HIV.

These special antibodies, scientists say, can neutralise different strains of the fast-mutating virus by binding to important yet difficult-to-access regions of the virus surface that don’t vary much from strain to strain.

Prof Kaleebu explained that this new approach is based on learning what the body does. “So what people are doing is that in some of these [HIV] infected people, after a long time, they produce very good bnAbs that can neutralise the virus –in a few individuals,” he said.

“So they are now going back to germline-targeting vaccines that will go to the B cells, lymph node, and specifically target those right B cells to produce those right antibodies as a vaccine. They are rare but they can be developed but how you develop them is to engineer a vaccine to do that,” he added.

Information from the website of the International Aids Vaccine Initiative (IAVI) indicates that a phase one trial is going on for two experimental HIV vaccine candidates which are based on RNA technology.

“Engineered HIV envelope proteins delivered through messenger RNA and designed to target germline B cells and guide their maturation toward the development of neutralising antibody responses,” information from the agency reads.

Phase one trials in humans assess the safety of the candidate, Phase II trials further assess safety as well as assess immunogenicity, and Phase III trials assess the efficacy of the candidate.

The new failure of the vaccine comes about 30 years after another trial for another experimental HIV prevention vaccine in Uganda failed, according to information from the Joint Clinical Research Centre (JCRC) and the National Institutes of Health of the United States. The vaccine that failed in 1990s, JCRC said, was developed in France while the one whose trial was stopped this year had an experimental vaccine candidate made by the Switzerland-based EuroVacc Foundation.