| dc.description.abstract | 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. Crosssubtype
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. | en |
