A spate of news coverage on the results of the Phase I IAVI G001 HIV vaccine clinical trial reflects current public interest in vaccine development amid the ongoing COVID-19 pandemic. Data from the proof-of-concept IAVI G001 trial were presented in February at the virtual HIV Research for Prevention conference by William Schief, Ph.D., a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center (NAC) at Scripps Research in La Jolla, California. Schief’s laboratory developed the experimental immunogen tested in IAVI G001, which ultimately demonstrated success in stimulating production of rare immune cells needed to start the process of generating HIV broadly neutralizing antibodies (bnAbs).
Schief and his colleagues have been working for over a decade to design the “holy grail” of vaccines – an HIV vaccine that provides broad and potent protection against the circulating variants of HIV. Their strategy is to engineer a multi-step vaccine regimen that provides protection against HIV infection by stimulating many different types of bnAbs. IAVI G001 represents the first step in that strategy. The goal of the 48-volunteer trial was to test whether the vaccine would stimulate naïve B cells with specific properties that produce precursors to a certain type of bnAb. This is called a “germline targeting” approach. In IAVI G001, 97% of participants who were vaccinated developed the desired type of B cells. These results establish proof of principle for germline targeting in humans and support extending this strategy to further develop the B cells and to target production of other HIV bnAbs. Researchers think the germline targeting strategy could also be applied to vaccines for other challenging pathogens such as influenza, dengue, Zika, and hepatitis C viruses and the malaria parasite.
As a next step, IAVI and Scripps Research are partnering with the biotechnology company Moderna toward replicating the results of IAVI G001, this time through mRNA-delivery of the this and other immunogens. mRNA technology has the potential to significantly accelerate the pace of HIV vaccine development as it has for COVID-19 vaccines. A variety of articles on IAVI G001 published in April have focused on this aspect, which is top of mind as Pfizer’s and Moderna’s mRNA-based COVID-19 vaccines continue to be rolled out. Only future clinical trials will tell if the mRNA platform holds the same promise for HIV.