The antibody response in HIV-1-infected donors

Abstract

Purpose of review-Although the goal of preventive HIV vaccine design is primarily the induction of broadly neutralizing antibodies (bNAbs), recent evidence suggests that a protective response will also benefit from Fc effector functions. Here, we provide an update on the antibody response to HIV infection, including both Fab and Fc-mediated antibody responses. We also highlight recent studies showing the interplay between these functions, focusing primarily on studies published in the last year.Recent findings-Identification and characterization of bNAb donors continues to provide insights into viral factors that are potentially translatable to vaccine design. Improved and more diverse measures of Fc effector function, and modulators thereof, are enabling a deeper understanding of their role in infection. New data providing mechanistic links between the innate and adaptive humoral immune responses are creating exciting opportunities for vaccine strategies, with the aim of eliciting a polyfunctional protective response.Summary-New insights into the overall humoral response to HIV infection are defining diverse and synergistic mechanisms required for antibody protection from HIV through vaccination.

IgG3 enhances neutralization potency and Fc effector function of an HIV V2-specific broadly neutralizing antibody

“…The variable and constant regions of antibodies are often treated as two structurally and functionally distinct components, despite growing evidence of co-operation between them [18, 70]. We recently showed that early and potent Fc effector polyfunctionality predicted the development of neutralizing activity, highlighting that these different functions of antibodies are intrinsically linked [55].…”

Highly protective antimalarial antibodies via precision library generation and yeast display screening

“…4 ; Guo et al, 2019 ). Natural antibody development samples a heavily biased sequence space due to SHM targeting preferences, which impedes the natural development of effective antibodies against various diseases ( Julien and Wardemann, 2019 ; Murugan et al, 2020 ; Richardson and Moore, 2019 ; Schramm and Douek, 2018 ). Prior studies showed minimal correlation between SHM and immune protection for PfCSP-specific antibodies, and our findings support a hypothesis that natural antimalarial antibody development may be limited by incomplete sampling of rare mutations in vivo ( Schramm and Douek, 2018 ; Shen et al, 2020 ; Sheng et al, 2017 ; Fig.…”

“…4 ). Rare mutations can play an important role in protective antibody development for infections with repeated antigen exposure like malaria and HIV-1 ( Julien and Wardemann, 2019 ; Murugan et al, 2020 ; Saunders et al, 2019 ; Shen et al, 2020 ) where chronic or repeated infection can sometimes enable the development of improbable mutations which achieve remarkable protective activity ( Richardson and Moore, 2019 ; Saunders et al, 2019 ).…”