Vaccination induces HIV broadly neutralizing antibody precursors in humans.
rct · Level II
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- Record sourced from PubMed, PMID 36454825.
- Also identified by DOI 10.1126/science.add6502 and PMC identifier 11103259.
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Abstract
Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01<sub>B</sub> had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.
Medical subject headings
- AIDS Vaccines
- Broadly Neutralizing Antibodies
- HIV Infections
- HIV Antibodies
- Germ Cells
- Immunoglobulin Light Chains
- Immunoglobulin Heavy Chains