Broadly neutralizing antibodies (bnAbs) are known to protect against HIV infection. However, there are challenges to triggering bnAbs through vaccination and bnAbs rarely develop during infection. In humans, bnAb-precursor B cells are rather uncommon.

Now, a first-in-human test evaluated the safety of a germline targeting priming vaccine candidate—eOD-GT8 60mer nanoparticle adjuvanted with AS01B—and whether it would induce bnAb-precursor responses. The promising results show that the germline-targeting priming immunogen was safe and induced bnAb-precursor responses in 26 of the 27 vaccine recipients (97%).

This work is published in Science, in the paper, “Vaccination induces HIV broadly neutralizing antibody precursors in humans.”

A preventative HIV vaccine is urgently needed to put an end to the HIV/AIDS pandemic. A vaccine that elicits the production of bnAbs, which can recognize the globally diverse strains of HIV and protect against infection, could provide an ideal solution.

For some pathogens that have eluded the development of vaccines that induce broad immunity, bnAbs have been considered. These bnAbs bind to relatively conserved epitopes on membrane glycoproteins of each pathogen.

A goal of some vaccine development programs is to create vaccines that could consistently induce these bnAbs. Now, a Phase I clinical trial provides promising results for a bnAb HIV vaccine. An effective bnAb HIV vaccine needs to recruit rare bnAb precursors through germline-targeting to produce HIV bnAbs.

This new study presents results from a randomized, double-blind, placebo-controlled Phase I 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%).

They 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 study, the authors wrote, “establishes clinical proof of concept for the germline-targeting vaccine design priming strategy, supports development of boosting regimens to generate VRC01-class bnAb responses against HIV, and encourages application of the germline-targeting strategy to other targets in HIV and other pathogens.”

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