B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies

Samantha M. Townsley, Gina C. Donofrio, Ningbo Jian, David J. Leggat, Vincent Dussupt, Letzibeth Mendez-Rivera, Leigh Anne Eller, Lauryn Cofer, Misook Choe, Philip K. Ehrenberg, Aviva Geretz, Syna Gift, Rebecca Grande, Anna Lee, Caroline Peterson, Mary Bryson Piechowiak, Bonnie M. Slike, Ursula Tran, M. Gordon Joyce, Ivelin S. GeorgievMorgane Rolland, Rasmi Thomas, Sodsai Tovanabutra, Nicole A. Doria-Rose, Victoria R. Polonis, John R. Mascola, Adrian B. McDermott, Nelson L. Michael, Merlin L. Robb, Shelly J. Krebs*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14–43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.

Original languageEnglish
Pages (from-to)564-578.e9
JournalCell Host and Microbe
Issue number4
StatePublished - 14 Apr 2021
Externally publishedYes


  • B cells
  • HIV
  • acute infection
  • broadly neutralizing antibodies
  • founder envelope


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