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|Oct. 2017||Wagner GA, Landais E, Caballero G, Phung P, Kosakovsky Pond SL, Poignard P, Richman DD, Little SJ, Smith DM. Intrasubtype B HIV-1 superinfection correlates with delayed neutralizing antibody response. J Virol. 2017;91(17). PMID: 28615205. PMCID: 5553187.|
An effective antibody-based HIV vaccine has not yet been achieved. Significant gaps of knowledge remain regarding correlates of protection and induction of HIV-specific neutralizing antibodies (NAb). HIV superinfection, i.e., re-infection of an individual, provides a unique opportunity to address these gaps because (a) failure of HIV infection to provide immunity is analogous to vaccine failure to provide protection, and (b) NAb development is modulated by viral genetic diversity.
We examined associations between the development of NAb and the occurrence of superinfection in a well-characterized, antiretroviral-therapy-naive, primary HIV infection cohort. Deep sequencing was applied to blood plasma samples to detect superinfection. We compared the NAb activity against autologous and heterologous viruses between 10 participants with intrasubtype B superinfection and 19 monoinfected controls, matched to duration of infection and risk behavior. Within the first six months, individuals who would later become superinfected had weaker NAb activity against autologous and subtype-specific neutralization-sensitive viruses. Between two and three years after primary infection, NAb levels strengthened and reached those of controls. One superinfected individual developed the broadest and most potent NAb response in the cohort consistent with the notion that antigenic diversity can prime certain pathways of breadth development in some individuals.
Our findings suggest that within the first year after HIV infection, a relatively weak NAb response increases susceptibility to superinfection in the face of repeated exposures. These findings could inform HIV vaccine design by providing testable correlates of protection from initial HIV infection. These data also suggest that an effective antibody-based vaccine will likely need to elicit humoral immune responses in a different and more directed way than in natural infection to achieve broad protection.