Back to Search Start Over

HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies.

Authors :
Hahn WO
Parks KR
Shen M
Ozorowski G
Janes H
Ballweber-Fleming L
Woodward Davis AS
Duplessis C
Tomai M
Dey AK
Sagawa ZK
De Rosa SC
Seese A
Siddaramaiah LK
Stamatatos L
Lee WH
Sewall LM
Karlinsey D
Turner HL
Rubin V
Furth S
MacPhee K
Duff M
Corey L
Keefer MC
Edupuganti S
Frank I
Maenza J
Baden LR
Hyrien O
Sanders RW
Moore JP
Ward AB
Tomaras GD
Montefiori DC
Rouphael N
McElrath MJ
Source :
MedRxiv : the preprint server for health sciences [medRxiv] 2024 May 09. Date of Electronic Publication: 2024 May 09.
Publication Year :
2024

Abstract

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.<br />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.

Details

Language :
English
Database :
MEDLINE
Journal :
MedRxiv : the preprint server for health sciences
Accession number :
38766048
Full Text :
https://doi.org/10.1101/2024.05.08.24306957