Precise targeting of HIV broadly neutralizing antibody precursors in humans.
rct · Level II
Where this comes from
- Record sourced from PubMed, PMID 40373114.
- Also identified by DOI 10.1126/science.adv5572 and PMC identifier 12313413.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
A protective HIV vaccine will need to induce broadly neutralizing antibodies (bnAbs) in humans, but priming rare bnAb precursor B cells has been challenging. In a double-blinded, placebo-controlled phase 1 human clinical trial, the recombinant, germline-targeting envelope glycoprotein (Env) trimer BG505 SOSIP.v4.1-GT1.1, adjuvanted with AS01<sub>B</sub>, induced bnAb precursors of the VRC01-class at a high frequency in the majority of vaccine recipients. These bnAb precursors, which target the CD4 receptor binding site, had undergone somatic hypermutation characteristic of the VRC01-class. A subset of isolated VRC01-class monoclonal antibodies neutralized wild-type pseudoviruses and was structurally extremely similar to bnAb VRC01. These results further support germline-targeting approaches for human HIV vaccine design and demonstrate atomic-level manipulation of B cell responses with rational vaccine design.
Medical subject headings
- AIDS Vaccines
- Antibodies, Monoclonal
- Broadly Neutralizing Antibodies
- env Gene Products, Human Immunodeficiency Virus
- HIV Antibodies
- HIV Infections
- HIV-1