FRIDAY, March 30 (HealthDay News) -- Sequential HIV infections lead to the development of a broad neutralizing antibody (NAb) response, according to a study published online March 29 in PLoS Pathogens.
Noting that NAb breadth is positively associated with viral diversity, Valerie Cortez, from the University of Washington in Seattle, and colleagues investigated whether individuals infected with multiple HIV-1 strains develop a broad NAb response as a result of antigenic stimulation by distinct viruses. Plasma samples were collected from 12 superinfected women and three singly-infected women matched to each case. Samples were tested against a panel of eight viruses, representing four different HIV-1 subtypes, at matched time points approximately five years post-initial infection.
The researchers found that, post-superinfection, superinfected women developed broader NAb responses than singly-infected individuals (relative risk, 1.68). The association persisted even after controlling for NAb breadth developed before superinfection, CD4+ T cell count, and viral load. Significantly greater potency was seen in superinfected individuals compared with controls, in both unadjusted and adjusted analyses. Two of the superinfected individuals were able to neutralize variants from four different subtypes at plasma dilutions >1:300. In both of these individuals, cross-subtype breadth was seen within a year of superinfection (within 1.5 years of 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," the authors write.
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