Clinical trials for experimental HIV vaccines based on mRNA technology begin in United States

Scientists urge African leaders to demand fair licensing following clinical trials of an HIV vaccine candidate.

One remarkable thing about the COVID-19 pandemic was how quickly a vaccine was developed to combat the virus. A process that normally spans a decade or more — dozens of clinical trials, terse patent negotiations, complex roll-out strategies — was condensed into less than one year. mRNA, messenger ribonucleic acids that elicit an immune response from cells before degrading, provided a quick and safe solution to a global health threat.

mRNA technology has been under development since the 1960s, but its success in combatting coronavirus has resulted in renewed interest in using the technology for other diseases. One of these is another pandemic that has killed an estimated 36 million people since it was recognised in 1981 — human immunodeficiency virus, better known as HIV.

The United States’ National Institute of Allergy and Infectious Diseases (NIAID) announced in March the launch of a phase I clinical trial evaluating three experimental HIV vaccines based on an mRNA platform. NIAID director Anthony Fauci said that while finding an HIV vaccine had proven “a daunting scientific challenge”, there was now “an exciting opportunity to learn whether mRNA technology can achieve similar results against HIV infection.”

Elsewhere in the US, the first human trial of an mRNA vaccine against HIV launched in January this year. The vaccine candidate, developed with pharmaceutical company Moderna, is being administered to 56 HIV-negative adults in Washington, Atlanta, Seattle and San Antonio.

Those involved in the trial are cautious with their enthusiasm. The HIV virus is a much more complex target for mRNAs, says Dagna Laufer, vice president of clinical trial development at the International AIDS Vaccine Initiative (IAVI), which is co-managing the trial —dubbed IAVI G002.

If shown to have an acceptable safety profile and able to induce the desired immune response, the vaccine candidates could be the first stage of a multi-step vaccine regimen. But we will need to undertake multiple trials to achieve this goal, and these trials will be conducted over at least a five- to ten-year period."

Dagna Laufer, vice president of clinical trial development, International AIDS Vaccine Initiative (IAVI)

Estimated number of people (all ages) living with HIV (1990-2020)

What makes HIV such a difficult disease to tackle is that it is a retrovirus, meaning it stays in the body forever by copying its genome and inserting it into the host’s cells. This is unlike COVID-19, which is an RNA virus that is shed by the body after a few weeks. To protect against HIV, the mRNA vaccine must do more than just elicit a temporary immune response; it must encourage the body to produce a special type of B-cells — broadly neutralizing antibodies — that can suppress HIV long-term.

Achieving this is incredibly tricky, not least because the message protein that can do this has not yet been conclusively identified. But non-mRNA vaccines for HIV are also struggling to take off. A trial for a non-mRNA vaccine developed by pharmaceutical company Johnson & Johnson was abandoned in 2021 after it emerged that the vaccine candidate provided about 25 per cent protection against HIV — a level considered too low to be effective.

Still, IAVI and Moderna are planning for success. A first trial on macaques in 2021 showed that their HIV vaccine candidate delivered a message that caused the monkeys to make antibodies that could neutralize an HIV infection. The next trial, IAVI G003, is scheduled to start by mid-2022 and will be conducted at clinical research centers in Rwanda and South Africa, Laufer tells SciDev.Net. The idea behind the phase II trial is that African scientists will play “a leadership role” both in conducting the study and analyzing the resulting data.

Global South production

The shift of the trial to Africa may go some way towards addressing another major issue with vaccine trials for HIV — the lack of involvement of those most affected by the virus.

According to the World Health Organization, more than two-thirds of the 25 million people living with HIV live in Africa, where the risk of dying from the disease is also the highest.

There are a number of reasons for this: a lack of access to quality healthcare, the cost of antiretroviral therapy, and the stigma associated with HIV. These factors combine to make Africa a less interesting target for pharmaceutical companies.

This has been evident during the COVID-19 pandemic. Despite being home to 1.3 billion people, only 375 million vaccine doses had been administered in Africa as of March this year, according to the WHO.

For this reason, there is growing concern about access among those monitoring the development of mRNA and conventional vaccines for HIV. There is no certainty whether, if successful, an mRNA HIV vaccine will be available to those who need it most.

“Even if we do get an HIV vaccine, we have to do better than COVID-19 in terms of equity and access,” says Mitchell Warren, the executive director of AVAC, a global advocacy group for HIV prevention.

Warren says that conducting clinical trials in Africa is a good first step, but that this needs to be followed up with true collaboration. “Africa is not just a clinical trial site, Africa is a continent of [more than] 50 countries with leading researchers, with vaccine manufacturing capacity, with growing regulatory expertise,” he told SciDev.Net.

“If African partners are hosting clinical trials, they should also demand immediate access and registration of the final product. We do not want the research to be done there for a license elsewhere.”

Laufer says the IAVI G002 trial is “not yet on a product development pathway”. But issues around who gets to produce the vaccine, should it be successful, were highlighted with COVID-19. Moderna did not share the formula for its COVID-19 vaccine, but it has pledged not to enforce patents against companies manufacturing COVID-19 vaccines for 92 low- and middle-income countries. Other vaccine developers such as Pfizer and AstraZeneca also retained the patent information on how to make their vaccines. In response, the WHO and a South African consortium set up an mRNA technology transfer hub to create their own vaccines.

“Moderna has not proven itself to be generous when releasing the patent or making their COVID-19 mRNA vaccine available in developing countries to date,” says Monica Gandhi, the director of the University of California San Francisco Center for AIDS Research. “Therefore, we will need government and community pressure on the company to share its technology with the rest of the world, given that HIV incidence is highest in developing countries.”

Moderna did not respond to a request for comment from SciDev.Net. However, the company revealed plans in March to open an mRNA vaccine production facility in Kenya, which would manufacture the COVID-19 vaccine, among others. The company will make an initial US$500 million investment in the facility, but did not confirm whether some of this money would go towards work on the HIV vaccine.

For Warren, the Moderna announcement is good news because, he says, it will increase production capacity in the global South and diversify vaccine manufacturing. Having a product made within the region could also go some way towards alleviating vaccine hesitancy in Africa, where people have reported reluctance to accept COVID-19 vaccines due to a mistrust of global corporations.

“Any centralized corporate control of the mRNA platforms really feeds inequity,” Warren says. “We need distributed manufacturing. For a global pandemic you cannot rely on a single manufacturer.”

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