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Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual

  1. Author:
    Krebs, Shelly J.
    Kwon, Young D.
    Schramm, Chaim A.
    Law, William H.
    Donofrio, Gina
    Zhou, Kenneth H.
    Gift, Syna
    Dussupt, Vincent
    Georgiev, Ivelin S.
    Schatzle, Sebastian
    McDaniel, Jonathan R.
    Lai, Yen-Ting
    Sastry, Mallika
    Zhang, Baoshan
    Jarosinski, Marissa C.
    Ransier, Amy
    Chenine, Agnes L.
    Asokan, Mangaiarkarasi
    Bailer, Robert T.
    Bose, Meera
    Cagigi, Alberto
    Cale, Evan M.
    Chuang, Gwo-Yu
    Darko, Samuel
    Driscoll, Jefferson
    Druz, Aliaksandr
    Gorman, Jason
    Laboune, Farida
    Louder, Mark K.
    McKee, Krisha
    Mendez, Letzibeth
    Moody, M. Anthony
    O'Sullivan, Anne Marie
    Owen, Christopher
    Peng, Dongjun
    Rawi, Reda
    Sanders-Buell, Eric
    Shen, Chen-Hsiang
    Shiakolas, Andrea R.
    Stephens,Tyler
    Tsybovsky,Yaroslav
    Tucker, Courtney
    Verardi, Raffaello
    Wang, Keyun
    Zhou, Jing
    Zhou, Tongqing
    Georgiou, George
    Alam, S. Munir
    Haynes, Barton F.
    Rolland, Morgane
    Matyas, Gary R.
    Polonis, Victoria R.
    McDermott, Adrian B.
    Douek, Daniel C.
    Shapiro, Lawrence
    Tovanabutra, Sodsai
    Michael, Nelson L.
    Mascola, John R.
    Robb, Merlin L.
    Kwong, Peter D.
    Doria-Rose, Nicole A.

  2. Author Address

    WRAIR, US Mil HIV Res Program, Silver Spring, MD USA.Henry Jackson Fdn, Bethesda, MD USA.NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN USA.Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA.Duke Univ, Sch Med, Durham, NC USA.Ctr HIV AIDS Vaccine Immunol Immunogen Discovery, Durham, NC USA.Frederick Natl Lab Canc Res, Electron Microscopy Lab, Canc Res Technol Program, Frederick, MD USA.Columbia Univ, New York, NY 10027 USA.
    1. Year: 2019
    2. Date: MAR 19
    3. Epub Date: 2019 03 12
  2. Journal: IMMUNITY
  3. CELL PRESS,
    1. 50
    2. 3
    3. Pages: 677-+
  5. Type of Article: Article
  6. ISSN: 1074-7613
  1. Abstract:

    Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.immuni.2019.02.008
  3. PMID: 30876875
  4. View record in Web of Science®
  5. WOS: 000461660500018

Library Notes

  1. Fiscal Year: FY2018-2019
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