HIV-1 Superinfection in Women Broadens and Strengthens the Neutralizing Antibody Response

PLoS Pathogens

Katherine Odem-Davis¹  Julie Overbaugh¹  R. Scott McClelland²  Walter Jaoko²  Valerie Cortez³ 

[1] Department of Epidemiology, University of Washington, Seattle, Washington, United States of America;Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America;Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, Washington, United States of America

关键词: HIV-1;    Viral load;    T cells;    Antibodies;    Superinfection;    Antibody response;    Monoclonal antibodies;    Antigens;   

DOI  :  10.1371/journal.ppat.1002611

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Identifying naturally-occurring neutralizing antibodies (NAb) that are cross-reactive against all global subtypes of HIV-1 is an important step toward the development of a vaccine. Establishing the host and viral determinants for eliciting such broadly NAbs is also critical for immunogen design. NAb breadth has previously been shown to be positively associated with viral diversity. Therefore, we hypothesized that superinfected individuals develop a broad NAb response as a result of increased antigenic stimulation by two distinct viruses. To test this hypothesis, plasma samples from 12 superinfected women each assigned to three singly infected women were tested against a panel of eight viruses representing four different HIV-1 subtypes at matched time points post-superinfection (∼5 years post-initial infection). Here we show superinfected individuals develop significantly broader NAb responses post-superinfection when compared to singly infected individuals (RR = 1.68, CI: 1.23–2.30, p = 0.001). This was true even after controlling for NAb breadth developed prior to superinfection, contemporaneous CD4+ T cell count and viral load. Similarly, both unadjusted and adjusted analyses showed significantly greater potency in superinfected cases compared to controls. Notably, two superinfected individuals were able to neutralize variants from four different subtypes at plasma dilutions >1∶300, suggesting that their NAbs exhibit elite activity. Cross-subtype breadth was detected within a year of superinfection in both of these individuals, which was within 1.5 years of their initial infection. These data suggest that sequential infections lead to augmentation of the NAb response, a process that may provide insight into potential mechanisms that contribute to the development of antibody breadth. Therefore, a successful vaccination strategy that mimics superinfection may lead to the development of broad NAbs in immunized individuals.

【 授权许可】

CC BY