Journal: medRxiv / Year: 2024 Title: HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum induces human autologous tier-2 neutralizing antibodies. 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 ...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 ...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.
Entire : BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies ...
Entire
Name: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies gp120-GH and base from participant 09
Components
Complex: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies gp120-GH and base from participant 09
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Supramolecule #1: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies ...
Supramolecule
Name: BG505 SOSIP.664 in complex with wk26 human polyclonal antibodies gp120-GH and base from participant 09 type: complex / ID: 1 / Parent: 0 Details: Polyclonal antibodies isolated from human serum and digested to Fab using papain
Source (natural)
Organism: Homo sapiens (human)
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Experimental details
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Structure determination
Method
negative staining
Processing
single particle reconstruction
Aggregation state
particle
-
Sample preparation
Concentration
0.03 mg/mL
Buffer
pH: 7.4 Component:
Concentration
Name
50.0 mM
Tris
150.0 mM
sodium chloride
Staining
Type: NEGATIVE / Material: uranyl formate
Grid
Model: Homemade / Material: COPPER / Mesh: 400 / Support film - Material: PARLODION / Support film - topology: CONTINUOUS
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Electron microscopy
Microscope
FEI TECNAI F20
Electron beam
Acceleration voltage: 120 kV / Electron source: FIELD EMISSION GUN
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