Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

Syna Kuriakose Gift, Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Sebastian Molnar, Gina Donofrio, Samantha Townsley, Agnes L. Chenine, Meera Bose, Hung V. Trinh, Brittani M. Barrows, Somchai Sriplienchan, Suchai Kitsiripornchai, Sorachai Nitayapan, Leigh Anne Eller, Mangala Rao, Guido Ferrari, Nelson L. Michael, Julie A. Ake, Shelly J. KrebsMerlin L. Robb, Sodsai Tovanabutra, Victoria R. Polonis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = 20.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = 20.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection.

Original languageEnglish
JournalJournal of Virology
Volume97
Issue number2
DOIs
StatePublished - Feb 2023
Externally publishedYes

Keywords

  • ADCC
  • CRF01_AE
  • HIV-1
  • V1V2
  • autologous neutralization
  • neutralization breadth
  • viral load set point

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