New HIV Vaccine Development Approach Promising
By Mary Hearty
The phase 1 clinical trial of a novel strategy to develop an effective HIV vaccine shows that the vaccine induced the targeted response in 97% (35 out of 36) of those who were vaccinated.
The researchers behind the strategy are drawn from four institutions including the International AIDS Vaccine Initiative (IAVI), Scripps Research, Fred Hutchinson Cancer Center (Fred Hutch) and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC).
In a paper published in Science on December 2, 2022, the scientists reveal critical new insights into their novel vaccine strategy, which involves a stepwise approach to producing antibodies capable of targeting a wide range of HIV variants.
“The data we are publishing in Science demonstrates for the first time that one can design a vaccine that elicits made-to-order antibodies in humans. We specified in advance certain molecular properties of the antibodies that we wanted to elicit, and the results of this trial show that our vaccine antigen consistently induced precisely those types of antibodies,” says co-senior author William Schief, a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center, whose laboratory developed the vaccine antigen.
“We believe this vaccine design strategy will be essential to make an HIV vaccine and may help the field create vaccines for other difficult pathogens.”
This comes at a time when more than one million new HIV infections occur each year, highlighting the need for effective HIV vaccines.
The Phase I trial, known as IAVI G001, tested the first stage in a multi-stage HIV vaccine regimen the researchers are developing. Importantly, the study also provides a detailed immunological analysis of the vaccine responses.
“HIV represents an area of dire unmet need across the world, which is what makes the findings from our Phase I clinical trial so encouraging,” says Mark Feinberg, president and CEO of IAVI. “Through the close-knit collaboration of many different scientists, disciplines, and institutions, we are that much closer to designing an effective vaccine that could help end the HIV pandemic.”
Priming the immune system
According to the researchers, broadly neutralizing antibodies (bnAbs) are a rare type of antibodies that can fight and protect against many different variants of a virus — including HIV. This is why scientists have tried to develop an HIV vaccine that induces bnAbs, but thus far without success.
The researchers in the study are using a strategy known as ‘germline targeting’ to eventually produce bnAbs that can protect against HIV.
The first step of germline targeting involves stimulating the rare immune cells — known as bnAb-precursor B cells — that can eventually evolve into the cells that produce the bnAbs needed to block the virus.
To accomplish this first step, the researchers designed a customized molecule — known as an immunogen — that would “prime” the immune system and elicit responses from these rare bnAb-precursor cells.
The overarching goal of the IAVI G001 trial was to determine if the vaccine had an acceptable safety profile and could induce responses from these bnAb-precursor B cells.
“Through extensive safety and tolerability monitoring during the trial, we showed the vaccine had a favorable safety profile, while still inducing the necessary target cells,” says study author Dagna Laufer, vice president and head of clinical development at IAVI. “This represents a large step forward in developing an HIV vaccine that is both safe and effective.”
To determine if the targeted bnAb-precursor B cells were induced, the researchers carried out a sophisticated analytical process.
“The workflow of multidimensional immunological analyses have taken clinical trial evaluation to the next level,” says co-senior author Adrian McDermott, former chief of the Vaccine Immunology Program at the NIAID VRC. “In evaluating these important immunological factors, we helped show why the vaccine antigen was able to induce the targeted response in 97% of vaccine participants.”
With these promising data in hand spanning both safety and immune responses, the researchers will continue to iterate and design boosting immunogens that could eventually induce the desired bnAbs and provide protection against the virus.
These findings also come shortly after two additional studies in Immunity published in September 2022, which helped validate the germline-targeting approach for vaccinating against HIV.
“Working together with IAVI, Scripps Research, the VRC, GWU, additional investigators at Fred Hutch, and many others, this trial and additional analyses will help inform the design of the remaining stages of a candidate HIV vaccine regimen — while also enabling others in the field to develop vaccine strategies for additional viruses,” says McElrath.