Sequential immunization with antigens from different strains of HIV-1, influenza viruses or dengue viruses induced cross-neutralizing antibodies and enhanced the antibody responses against previous antigens. The characteristics of neutralizing antibodies induced by sequential immunization with different types of HPV L1VLPs are unclear. In this study, mice were primed with one or two types (HPV16 or HPV16/18) of L1VLPs, then boosted sequentially with HPV6/18/45/11/31/58 or HPV6/45/11/31/58 L1VLPs, and sera were analyzed with HPV pseudovirus-based neutralization assay. The results showed that neutralizing activities against earlier immunized vaccine types were enhanced gradually by subsequent immunizations, and low levels of neutralizing activities against non-vaccine types (HPV33/35/52/59/68) were also observed. After absorbing the immune sera with vaccine type (HPV16/18/45) L1VLPs, neutralizing activities against tested priming and boosting types (HPV16/18/58) decreased significantly, and that against non-vaccine type (HPV33) were also partially eliminated. Moreover, neutralizing activities against vaccine types (HPV16/58) were significantly reduced after absorbing with non-vaccine-type VLPs (HPV33/52). These data suggest that cross-neutralizing epitopes exist among different HPV L1VLPs. The cross-neutralizing activities against non-vaccine types and the enhanced neutralizing activities against earlier immunized vaccine types may be resulted from sequential boosting with these cross-neutralizing epitopes. These observations support for early vaccination with more types of L1VLPs derived from HPVs that cause serious threat to population. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.
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