A HIV-1 Gp41 Peptide-Liposome Vaccine Elicits Neutralizing Epitope-Targeted Antibody Responses in Healthy Individuals
This article has been Reviewed by the following groups
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
Background
HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys.
Methods
The HVTN133 phase 1 clinical trial ( NCT03934541 ) studied the MPER-peptide liposome immunogen in 24 HIV-1 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October 2019 and 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.
Results
The trial was stopped prematurely due to an anaphylaxis reaction in one participant ultimately attributed to vaccine-associated polyethylene glycol. The immunogen induced robust immune responses, including MPER+ serum and blood CD4+ T-cell responses in 95% and 100% of vaccinees, respectively, and 35% (7/20) of vaccine recipients had blood IgG memory B cells with MPER-bnAb binding phenotype. Affinity purification of plasma MPER+ IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations.
Conclusions
MPER-peptide liposomes induced gp41 serum neutralizing epitope-targeted antibodies and memory B-cell responses in humans despite the early termination of the study. These results suggest that the MPER region is a promising target for a candidate HIV vaccine.
Trial Registration
http://www.clinicaltrials.gov/ Identifier: NCT03934541
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) | 📘📘📘📘📘 -
