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TitleHIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies.
Journal, issue, pagesmedRxiv, Year 2024
Publish dateMay 9, 2024
PubMed AbstractStabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric ...Stabilized trimers preserving the native-like HIV envelope structure may be key components of a preventive HIV vaccine regimen to induce broadly neutralizing antibodies (bnAbs). We evaluated trimeric BG505 SOSIP.664 gp140, formulated with a novel TLR7/8 signaling adjuvant, 3M-052-AF/Alum, for safety, adjuvant dose-finding and immunogenicity in a first-in-healthy adult (n=17), randomized, placebo-controlled trial (HVTN 137A). The vaccine regimen appeared safe. Robust, trimer-specific antibody, B-cell and CD4+ T-cell responses emerged post-vaccination. Five vaccinees developed serum autologous tier-2 nAbs (ID50 titer, 1:28-1:8647) after 2-3 doses targeting C3/V5 and/or V1/V2/V3 Env regions by electron microscopy and mutated pseudovirus-based neutralization analyses. Trimer-specific, B-cell-derived monoclonal antibody activities confirmed these results and showed weak heterologous neutralization in the strongest responder. Our findings demonstrate the clinical utility of the 3M-052-AF/alum adjuvant and support further improvements of trimer-based Env immunogens to focus responses on multiple broad nAb epitopes.
KEY TAKEAWAY/TAKE-HOME MESSAGES: HIV BG505 SOSIP.664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched clade A, tier 2 virus, that map to diverse Env epitopes with relatively high titers. The novel adjuvant may be an important mediator of vaccine response.
External linksmedRxiv / PubMed:38766048 / PubMed Central
MethodsEM (single particle)
Resolution22.0 - 32.0 Å
Structure data

EMDB-40815: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies C3V5, V1V3, N611 and base from participant 017
Method: EM (single particle) / Resolution: 23.0 Å

EMDB-40816: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies gp41-N611/FP and base from participant 03
Method: EM (single particle) / Resolution: 32.0 Å

EMDB-40817: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies gp41-N611/FP and base from participant 07
Method: EM (single particle) / Resolution: 31.0 Å

EMDB-40818: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies gp120-GH and base from participant 09
Method: EM (single particle) / Resolution: 23.0 Å

EMDB-40819: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies C3V5, V1V3, gp41-GH/FP and base from participant 11
Method: EM (single particle) / Resolution: 22.0 Å

Source
  • Homo sapiens (human)

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