An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
Broadly neutralizing antibodies (bnAbs) that target the HIV gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand MPER bnAb precursors in monkeys. The HVTN133 phase 1 clinical trial ( NCT03934541 ) studied the MPER peptide-liposome immunogen in 24 HIV-1 seronegative individuals. Participants were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12. The trial was stopped prematurely due to an anaphylaxis reaction in one participant attributed to vaccine-associated polyethylene glycol. The immunogen induced MPER-specific serum antibodies and CD4+ T-cell responses in 95% and 85% of vaccinees, respectively, and 35% of vaccine recipients had circulating IgG+ memory B cells with an MPER-bnAb binding phenotype. Affinity purification of plasma MPER-specific IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations and tier 2 HIV-1 neutralizing B cell clonal lineages were isolated from MPER-reactive B cells. These results demonstrate that the HIV gp41 MPER region is a promising target for induction of heterologous neutralizing antibodies by a candidate HIV vaccine.
Trial Registration
http://www.clinicaltrials.gov/ Identifier: NCT03934541
Funding
National Institutes of Health, Bill and Melinda Gates Foundation
Article activity feed
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Winfried Weissenhorn
Review 2: "A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals"
Reviewers generally support the study's methodology and findings but raise concerns about the neutralization data's precision and the presence of polyethylene glycol (PEG) in the vaccine formulation, which led to an adverse reaction in the phase 1 clinical trial.
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Xueling Wu
Review 1: "A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals"
Reviewers generally support the study's methodology and findings but raise concerns about the neutralization data's precision and the presence of polyethylene glycol (PEG) in the vaccine formulation, which led to an adverse reaction in the phase 1 clinical trial.
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Strength of evidence
Reviewers: X Wu (Columbia University) | 📗📗📗📗◻️
W Weissenhorn (Institute of Structural Biology in Grenoble) | 📘📘📘📘📘 -
