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

• Published in: Cell host & microbe Vol. 29; no. 4; pp. 564 - 578.e9
• Main Authors: Townsley, Samantha M., Donofrio, Gina C., Jian, Ningbo, Leggat, David J., Dussupt, Vincent, Mendez-Rivera, Letzibeth, Eller, Leigh Anne, Cofer, Lauryn, Choe, Misook, Ehrenberg, Philip K., Geretz, Aviva, Gift, Syna, Grande, Rebecca, Lee, Anna, Peterson, Caroline, Piechowiak, Mary Bryson, Slike, Bonnie M., Tran, Ursula, Joyce, M. Gordon, Georgiev, Ivelin S., Rolland, Morgane, Thomas, Rasmi, Tovanabutra, Sodsai, Doria-Rose, Nicole A., Polonis, Victoria R., Mascola, John R., McDermott, Adrian B., Michael, Nelson L., Robb, Merlin L., Krebs, Shelly J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.04.2021
• Subjects: acute infection; B cells; B-Lymphocytes - immunology; Broadly Neutralizing Antibodies; Cell Line; env Gene Products, Human Immunodeficiency Virus - immunology; Epitopes - immunology; founder envelope; HIV; HIV Antibodies - immunology; HIV Infections - immunology; HIV Infections - virology; HIV-1 - immunology; Humans; Viral Envelope - immunology; Viremia; B cells; HIV; acute infection; broadly neutralizing antibodies; founder envelope
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2021.01.016

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. [Display omitted] •A reduction in total peripheral B cells associates with HIV neutralization breadth•The initial interaction of founder Env with naive B cells predicts bNAb development•Increased B cell engagement with founder Env increases activation and differentiation Investigating how HIV-infected patients develop broadly neutralizing antibodies can inform vaccine design. Townsley et al. show that elevated B cell interactions with the HIV founder envelope glycoprotein within the first month of infection lead to increased B cell activation and differentiation, which predict development of neutralization breadth years later.