Oral Presentation Lorne Infection and Immunity 2018

HIV superinfection fails to recruit memory B-cell responses and drive neutralization breadth (#37)

Penny Moore 1
  1. University of Witwatersrand and National Institute for Communicable Diseases, Johannesburg, South Africa

An effective HIV vaccine will likely need to elicit broadly neutralizing antibodies (bnAbs), and understanding factors that promote their development during infection could identify mechanisms that vaccine strategies could leverage. HIV superinfection has previously been associated with broader antibody responses, and offers an opportunity to assess how the human immune system responds to sequential exposure to two distinct HIV Envelope antigens.  Here, we characterized the neutralizing antibody responses (nAb) in five superinfected women from the CAPRISA 002 cohort and investigated mechanisms by which superinfection could promote bnAbs.  We show that superinfection did not boost memory nAb responses primed by the first infection, or promote nAb responses to epitopes conserved in both infecting viruses.  While one superinfected individual, CAP256, developed extremely potent bnAbs,  superinfection was not the driver of breadth in this donor.  Overall, we find that sequential exposure to two distinct Envelopes led to, at most, additive nAb breadth.  These data have important implications for vaccine design, as they suggest that sequential immunization with heterologous Envelopes, a major current focus of the HIV vaccine field, may not be sufficient to focus the immune response onto conserved epitopes on the HIV-1 Envelope.