An HIV-1 gp41 MPER liposome vaccine elicits neutralizing epitope-targeted antibody responses in HIV-seronegative individuals

Journal article

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 participants. 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 the polyethylene glycol component of the vaccine. 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.

Authors: Erdmann, N; Williams, WB; Walsh, SR; Cain, DW; Clark, M

• Alternative title: HIV-1 vaccination with gp41 MPER-peptide liposomes
• Publication status: Accepted
• Peer review status: Peer reviewed
• Publisher: Springer Nature
• Journal: Nature Communications
• Acceptance date: 2026-06-22
• EISSN: 2041-1723
• Language: English
• Keywords: HIV vaccine; liposome; immunogenicity; fusion proteins