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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
HIV-1 superinfection in women broadens and strengthens the neutralizing antibody response
PLoS Pathogens, Volume 8, No. 3, Article e1002611, Year 2012
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Description
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. © 2012 Cortez et al.
Authors & Co-Authors
Cortez, Valerie
United States, Seattle
University of Washington
United States, Seattle
Fred Hutchinson Cancer Research Center
Odem-Davis, Katherine S.
United States, Seattle
Fred Hutchinson Cancer Research Center
McClelland, Raymond Scott
United States, Seattle
University of Washington
Jaoko, Walter G.
Kenya, Nairobi
University of Nairobi
Overbaugh, Julie M.
United States, Seattle
Fred Hutchinson Cancer Research Center
Statistics
Citations: 70
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1371/journal.ppat.1002611
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Infectious Diseases
Participants Gender
Female