Naturally acquired HPV antibodies against subsequent homotypic infection: A large-scale prospective cohort study

Summary: Background: Although recent studies have suggested that naturally acquired Human papillomavirus (HPV) antibodies are partly protective against subsequent homotypic infection, the extent of protection remains indecisive. Here, we evaluate the protective effect of neutralizing and IgG antibodies simultaneously. Methods: In a cohort of 3634 women aged 18-45 years from the control arm of a phase III trial of the HPV-16/18 bivalent vaccine, participants were tested for neutralizing antibodies by pseudovirion-based neutralization assay (PBNA) and IgG antibodies by enzyme-linked immunosorbent assay (ELISA) at baseline. HPV-16/18 incident and persistent infections were identified using cervical specimens periodically collected during the 5·5 years of follow-up. The protective effects of HPV-16/18 neutralizing and IgG antibodies against homotypic infection were assessed using a Cox proportional hazard model. Findings: For the persistent infection (PI) endpoints of HPV-16/18 lasting for over 6/12 months, a prevalence of type-specific neutralizing antibodies was highly protective (6-month PI: hazard ratio (HR) = 0·16, 95% confidence interval (CI): 0·04, 0·65; 12-month PI: HR = 0·23, 95% CI: 0·06, 0·94), whereas a prevalence of IgG antibodies was associated with minor and non-significant protection (6-month PI: HR = 0·66, 95% CI: 0·40, 1·09; 12-month PI: HR = 0·66, 95% CI: 0·36, 1·20). After increasing the cut-off value to the median IgG level, the risk of 6-month PI was significantly lower in seropositive vs seronegative women (HR = 0·38, 95% CI: 0·18, 0·83). Interpretation: Naturally acquired antibodies are associated with a substantially reduced risk of subsequent homotypic infection. Funding: NSFC; The Fujian Province Health Education Joint Research Project; Xiamen Science and Technology Major Project; CIFMS; and Xiamen Innovax