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Structural and genetic convergence of HIV-1 neutralizing antibodies in vaccinated non-human primates

  1. Author:
    Cai, Fangping
    Chen, Wei-Hung
    Wu,Weimin
    Jones, Julia A.
    Choe, Misook
    Gohain, Neelakshi
    Shen, Xiaoying
    LaBranche, Celia
    Eaton, Amanda
    Sutherland, Laura
    Lee, Esther M.
    Hernandez, Giovanna E.
    Wu, Nelson R.
    Scearce, Richard
    Seaman, Michael S.
    Moody, M. Anthony
    Santra, Sampa
    Wiehe, Kevin
    Tomaras, Georgia D.
    Wagh, Kshitij
    Korber, Bette
    Bonsignori, Mattia
    Montefiori, David C.
    Haynes, Barton F.
    de Val, Natalia
    Joyce, M. Gordon
    Saunders, Kevin O.

  2. Author Address

    Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27708 USA.Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.Walter Reed Army Inst Res, Emerging Infect Dis Branch, Silver Spring, MD 20910 USA.Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA.NCI, Ctr Mol Microscopy, Ctr Canc Res, NIH, Frederick, MD 21701 USA.Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD USA.Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA.Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA.Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA.Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27708 USA.Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27708 USA.Los Alamos Natl Lab, Los Alamos, NM USA.
    1. Year: 2021
    2. Date: Jun
  2. Journal: PLOS PATHOGENS
  3. PUBLIC LIBRARY SCIENCE,
    1. 17
    2. 6
  5. Type of Article: Article
  6. Article Number: e1009624
  7. ISSN: 1553-7366
  1. Abstract:

    A primary goal of HIV-1 vaccine development is the consistent elicitation of protective, neutralizing antibodies. While highly similar neutralizing antibodies (nAbs) have been isolated from multiple HIV-infected individuals, it is unclear whether vaccination can consistently elicit highly similar nAbs in genetically diverse primates. Here, we show in three outbred rhesus macaques that immunization with Env elicits a genotypically and phenotypically conserved nAb response. From these vaccinated macaques, we isolated four antibody lineages that had commonalities in immunoglobulin variable, diversity, and joining gene segment usage. Atomic-level structures of the antigen binding fragments of the two most similar antibodies showed nearly identical paratopes. The Env binding modes of each of the four vaccine-induced nAbs were distinct from previously known monoclonal HIV-1 neutralizing antibodies, but were nearly identical to each other. The similarities of these antibodies show that the immune system in outbred primates can respond to HIV-1 Env vaccination with a similar structural and genotypic solution for recognizing a particular neutralizing epitope. These results support rational vaccine design for HIV-1 that aims to reproducibly elicit, in genetically diverse primates, nAbs with specific paratope structures capable of binding conserved epitopes.

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External Sources

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  2. DOI: 10.1371/journal.ppat.1009624
  3. View record in Web of Science®
  4. WOS: 000657946000001

Library Notes

  1. Fiscal Year: FY2020-2021
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