Neutralization of non-vaccine human papillomavirus pseudoviruses from the A7 and A9 species groups by bivalent HPV vaccine sera

Eve Draper, Sara Bissett, Rebecca Howell-Jones, Debbie Edwards, Graham Munslow, Katherine Soldan, Simon Beddows*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    51 Citations (Scopus)


    The majority of cervical cancers are associated with infection by one or more Human Papillomavirus (HPV) types from just two distinct Alpha-Papillomavirus species groups, A7 and A9. The extent to which the current HPV16/18 vaccines will protect against other genetically related HPV types is of interest to inform vaccine implementation, cervical disease surveillance and the development of second generation HPV vaccines. The aim of this study was to determine the frequency and titer of neutralizing antibodies against a range of A7 (18, 39, 45, 59, 68) and A9 (16, 31, 33, 35, 52, 58) HPV types using sera from individuals immunized with the bivalent HPV vaccine within the school-based, UK national HPV immunization programme. Serum samples were collected from 69 girls aged 13-14 years, a median 5.9 months (inter-quartile range, IQR, 5.7-6.0) after their third vaccine dose. Cross-neutralizing antibodies against HPV31, HPV33, HPV35 and HPV45 were common and strongly associated with the titer for the related vaccine-type, but were considerably lower (<1%) than their related vaccine type-specific response. The low prevalence of these HPV types in the population and the ages within the study cohort suggest these responses are due to vaccination. It is unclear whether such low levels of neutralizing antibodies would be sufficient to protect at the site of infection in the absence of other immune effectors but the coincidence with HPV types reported from efficacy studies is intriguing. The utility of neutralizing antibodies as surrogate markers of protection remains to be determined.

    Original languageEnglish
    Pages (from-to)8585-8590
    Number of pages6
    Issue number47
    Publication statusPublished - 3 Nov 2011

    Bibliographical note

    Funding Information:
    This work was supported by the UK Medical Research Council (grant number G0701217 ). We thank Dr. Rosemary McCann (Greater Manchester Health Protection Unit, U.K.), Dr. Ray Borrow and Elaine Stanford (Vaccine Evaluation/Seroepidemiology Unit, Manchester Royal Infirmary, U.K.) for coordinating the collection of the serum samples used in this study and Prof. Elizabeth Miller and Liz Sheasby (National Vaccine Evaluation Consortium, U.K.) for providing anonymized infant, HPV-naïve sera. We are grateful to Tom Nichols for helpful discussions on statistical analyses. We are indebted to Prof. John T. Schiller and Dr. Chris Buck (National Cancer Institute, Bethesda, U.S.A.) and Dr. H. Faust and Prof. J. Dillner (Malmö University Hospital, Malmö, Sweden) for helpful discussion and access to the majority of the pseudovirus clones used in this study.


    • Antibody
    • Human papillomavirus
    • Vaccine


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