Evaluation of vaccine-induced binding and neutralizing antibodies as correlates of risk of HPV

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Abstract

Background

Estimated vaccine efficacy (VE) at 15 years for a single dose of quadrivalent human papillomavirus (HPV) vaccine in adolescent girls in India exceeded 90% against persistent infection (PI) from HPV 6/11/16/18, similar to VE for two or three doses [1]. Binding and neutralizing antibodies were evaluated as correlates of risk.

Methods

HPV-specific antibody titers were measured by ELISA and pseudovirion-based neutralization assay on 25 PI cases of HPV 6, 11, 16, 18 and/or 31 and on 126 matched controls. HPV 31 was included, given cross-protection, to provide sufficient cases for analysis; limited numbers prevented assessment of correlates to each type. Age-adjusted logistic regression models assessed antibody biomarkers as correlates.

Results

HPV 18 binding antibody titers inversely correlated with PI: OR=0.62, 95%CI=(0.39, 0.99), p=0.045 per 10-fold titer increase. Our analysis identified no other correlate.

Conclusion

Higher HPV 18 titers were associated with a lower risk of PI with HPV 6/11/16/18/31.

The clinical trial is registered with ISRCTN, ISRCTN98283094 , and ClinicalTrials.gov, NCT00923702 .

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