Examining neutralizing antibody activity as an immune correlate of HIV-1 superinfection

Abstract

Background: HIV-1 superinfection occurs roughly half as frequently as initial infection, suggesting the HIV-1 immune response is partially protective of reinfection. Identifying immune correlates of superinfection will potentially elucidate protective responses that vaccine candidates should be designed to induce. Objective: To examine the role of neutralizing antibody (NAb) activity in protecting against HIV-1 superinfection. Design/Methods: In the largest assessment of pre-superinfection NAb activity to date, we quantified NAb breadth and potency, based on neutralization of 4 diverse Env variants, in samples from immediately before superinfection in 13 diverse superinfection cases from a cohort of female sex workers in Mombasa, Kenya. Using a case-control design, these measures were compared to those of 39 singly infected controls individually matched to each case based on time since initial infection and viral subtype. Results: In conditional logistic regression analyses, pre-superinfection or matched timepoint NAb breadth and potency were not associated with superinfection status [odds ratio =1.0, 95% confidence interval (0.52-1.93); and OR=0.93, 95% CI (0.75, 1.15) respectively]. These results remained unchanged after controlling for contemporaneous viral load and CD4 count. Further, the timing of superinfection post initial infection did not appear to modify the relationship between pre-superinfection NAb activity and risk of superinfection. Conclusion: Pre-superinfection NAb breadth and potency, as measured against heterologous viruses, did not influence the risk of superinfection amongst 13 diverse superinfection cases. This suggests that the breadth of the NAb response does not play a substantial role in protecting against superinfection, and indicates that a successful antibody-based vaccine will likely need to elicit a NAb response more robust than that found in chronic infection.