A Phase 1 clinical trial provides promising results for a broadly neutralizing antibody (bnAb) HIV vaccine, according to a new study. The findings of this first-in-humans test establish a clinical proof-of-principal for germline-targeting vaccine design for HIV and other intractable pathogens. A preventative HIV vaccine is urgently needed to put an end to the HIV/AIDS pandemic. One that elicits the production of broadly neutralizing antibodies (bnAbs), which can recognize the globally diverse strains of HIV and protect against infection, could provide an ideal solution. However, triggering bnAbs through vaccination has not yet been possible. One of the key challenges towards achieving this goal is that bnAbs rarely develop during infection, and, in humans, bnAb-precursor B cells are rather uncommon. An effective bnAb HIV vaccine will need to recruit rare bnAb precursors through germline-targeting to produce HIV bnAbs. Here, David Leggat and colleagues present results from a randomized, double-blind, placebo-controlled phase 1 clinical trial showing that a germline-targeting priming immunogen was safe and feasible, and induced bnAb-precursor responses in 26 of the 27 vaccine recipients (97%). Leggat et al. designed a germline-targeting, self-assembling nanoparticle immunogen, eOD-GT8, which presented 60 copies of an engineered HIV envelope protein containing mutations designed to enhance its affinity to recruit rare bnAb precursors. “The clinical trial reported by Leggat et al. provides persuasive human data supporting the concept of germline targeting,” writes Penny Moore in a related Perspective, which discusses the study’s findings and limitations in greater detail.
Science
Vaccination induces HIV broadly neutralizing antibody precursors in humans
2-Dec-2022