An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals

作者：Nathan Erdmann, Wilton B. Williams, Stephen R. Walsh, Derek W. Cain, Matthew Clark, Ryan Tuck, Sommer Holmes, Benae Clardy, Andrew Foulger, Robert E. Parks, Margaret Barr, Amanda Eaton, Kevin O. Saunders, Nicole Grunenberg, Paul T. Edlefsen, Paul Goepfert, Kristen W. Cohen, Janine Maenza, Kenneth H. Mayer, Hong‐Van Tieu, Magdalena E. Sobieszczyk, Edith Swann, Haiyan Lu, Stephen C. De Rosa, Zachary K. Sagawa, Bob C. Lin, Robin E. Carrol, Krisha McKee, Nicole A. Doria-Rose, Mark K. Louder, M. Anthony Moody, Christopher B. Fox, Guido Ferrari, Robert J. Edwards, Priyamvada Acharya, S. Munir Alam, Georgia D. Tomaras, David C. Montefiori, Peter B. Gilbert, M. Juliana McElrath, Lawrence Corey, Barton F. Haynes, Lindsey R. Baden, the NIAID HVTN 133 Study Group · 发表于：medRxiv · 年份：2024 · DOI：10.1101/2024.03.15.24304305 · 被引用次数：8 · 研究领域：HIV Research and Treatment、Immunotherapy and Immune Responses、T-cell and B-cell Immunology

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.