Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans

Wilton B Williams; S Munir Alam; Gilad Ofek; Nathaniel Erdmann; David C Montefiori; Michael S Seaman; Kshitij Wagh; Bette Korber; Robert J Edwards; Katayoun Mansouri; Amanda Eaton; Derek W Cain; Mitchell Martin; JongIn Hwang; Aria Arus-Altuz; Xiaozhi Lu; Fangping Cai; Nolan Jamieson; Robert Parks; Maggie Barr; Andrew Foulger; Kara Anasti; Parth Patel; Salam Sammour; Ruth J Parsons; Xiao Huang; Jared Lindenberger; Susan Fetics; Katarzyna Janowska; Aurelie Niyongabo; Benjamin M Janus; Anagh Astavans; Christopher B Fox; Ipsita Mohanty; Tyler Evangelous; Yue Chen; Madison Berry; Helene Kirshner; Elizabeth Van Itallie; Kevin O Saunders; Kevin Wiehe; Kristen W Cohen; M Juliana McElrath; Lawrence Corey; Priyamvada Acharya; Stephen R Walsh; Lindsey R Baden; Barton F Haynes

doi:10.1016/j.cell.2024.04.033

Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans

Cell. 2024 May 14:S0092-8674(24)00459-8. doi: 10.1016/j.cell.2024.04.033. Online ahead of print.

Authors

Wilton B Williams¹, S Munir Alam², Gilad Ofek³, Nathaniel Erdmann⁴, David C Montefiori⁵, Michael S Seaman⁶, Kshitij Wagh⁷, Bette Korber⁷, Robert J Edwards⁸, Katayoun Mansouri⁹, Amanda Eaton¹⁰, Derek W Cain⁸, Mitchell Martin⁹, JongIn Hwang⁹, Aria Arus-Altuz⁹, Xiaozhi Lu⁹, Fangping Cai⁸, Nolan Jamieson⁸, Robert Parks⁹, Maggie Barr⁹, Andrew Foulger⁹, Kara Anasti⁹, Parth Patel⁹, Salam Sammour⁹, Ruth J Parsons⁹, Xiao Huang⁹, Jared Lindenberger⁹, Susan Fetics⁹, Katarzyna Janowska⁹, Aurelie Niyongabo¹¹, Benjamin M Janus³, Anagh Astavans¹¹, Christopher B Fox¹², Ipsita Mohanty⁹, Tyler Evangelous⁹, Yue Chen⁹, Madison Berry⁹, Helene Kirshner⁹, Elizabeth Van Itallie⁹, Kevin O Saunders¹³, Kevin Wiehe⁸, Kristen W Cohen¹⁴, M Juliana McElrath¹⁴, Lawrence Corey¹⁴, Priyamvada Acharya¹⁵, Stephen R Walsh¹⁶, Lindsey R Baden¹⁷, Barton F Haynes¹⁸

Affiliations

¹ Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke School of Medicine, Durham, NC 27710, USA. Electronic address: wilton.williams@duke.edu.
² Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke School of Medicine, Durham, NC 27710, USA. Electronic address: munir.alam@duke.edu.
³ Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA; Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USA.
⁴ University of Alabama Medical Center, Birmingham, AL 35223, USA.
⁵ Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke School of Medicine, Durham, NC 27710, USA.
⁶ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
⁷ Los Alamos National Laboratory, Los Alamos, NM 87545, USA; New Mexico Consortium, Los Alamos, NM 87544, USA.
⁸ Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke School of Medicine, Durham, NC 27710, USA.
⁹ Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA.
¹⁰ Department of Surgery, Duke School of Medicine, Durham, NC 27710, USA.
¹¹ Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
¹² Access to Advanced Health Institute, Seattle, WA 98102, USA.
¹³ Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke School of Medicine, Durham, NC 27710, USA.
¹⁴ Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
¹⁵ Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA; Department of Surgery, Duke School of Medicine, Durham, NC 27710, USA; Department of Biochemistry, Duke School of Medicine, Durham, NC 27710, USA.
¹⁶ Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: swalsh@bwh.harvard.edu.
¹⁷ Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: lbaden@bwh.harvard.edu.
¹⁸ Duke Human Vaccine Institute, Duke School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke School of Medicine, Durham, NC 27710, USA; Department of Integrative Immunobiology, Duke School of Medicine, Durham, NC 27710, USA; Duke Global Health Institute, Duke School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@duke.edu.

PMID: 38761800
DOI: 10.1016/j.cell.2024.04.033

Abstract

A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.