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Immune Monitoring Reveals Fusion Peptide Priming to Imprint Cross-Clade HIV-Neutralizing Responses with a Characteristic Early B Cell Signature

  1. Author:
    Cheng, Cheng
    Duan, Hongying
    Xu, Kai
    Chuang, Gwo-Yu
    Corrigan, Angela R
    Geng, Hui
    O'Dell, Sijy
    Ou, Li
    Chambers, Michael
    Changela, Anita
    Chen, Xuejun
    Foulds, Kathryn E
    Sarfo, Edward K
    Jafari, Alexander J
    Hill, Kurt R
    Kong, Rui
    Liu, Kevin
    Todd, John P
    Tsybovsky,Yaroslav
    Verardi, Raffaello
    Wang, Shuishu
    Wang, Yiran
    Wu, Winston
    Zhou, Tongqing
    Arnold, Frank J
    Doria-Rose, Nicole A
    Koup, Richard A
    McDermott, Adrian B
    Scorpio, Diana G
    Worobey, Michael
    Shapiro, Lawrence
    Mascola, John R
    Kwong, Peter D

  2. Author Address

    Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA., Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21710, USA., Department of Ecology and Evolutionary Biology, University of Arizona, Tucson, AZ 85721, USA., Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA., Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@nih.gov., Vaccine Research Center, National Institutes of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.,
    1. Year: 2020
    2. Date: Aug 04
  2. Journal: Cell reports
    1. 32
    2. 5
    3. Pages: 107981
  4. Type of Article: Article
  5. Article Number: 107981
  6. ISSN: 2211-1247
  1. Abstract:

    The HIV fusion peptide (FP) is a promising vaccine target. FP-directed monoclonal antibodies from vaccinated macaques have been identified that neutralize up to ~60% of HIV strains; these vaccinations, however, have involved ~1 year with an extended neutralization-eclipse phase without measurable serum neutralization. Here, in 32 macaques, we test seven vaccination regimens, each comprising multiple immunizations of FP-carrier conjugates and HIV envelope (Env) trimers. Comparisons of vaccine regimens reveal FP-carrier conjugates to imprint cross-clade neutralizing responses and a cocktail of FP conjugate and Env trimer to elicit the earliest broad responses. We identify a signature, appearing as early as week 6 and involving the frequency of B cells recognizing both FP and Env trimer, predictive of vaccine-elicited breadth ~1 year later. Immune monitoring of B cells in response to vaccination can thus enable vaccine insights even in the absence of serum neutralization, here identifying FP imprinting, cocktail approach, and early signature as means to improve FP-directed vaccine responses. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2020.107981
  3. PMID: 32755575
  4. View record in Web of Science®
  5. WOS: 000557812600006
  6. PII : S2211-1247(20)30966-9

Library Notes

  1. Fiscal Year: FY2019-2020
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