First generation HPV vaccines (Cervarix® and Gardasil®) have demonstrated almost 100% efficacy against the development of cervical cancer precursors associated with the vaccine-incorporated genotypes HPV16/18. One unanticipated benefit of HPV vaccination is that the vaccines also display a degree of cross-protection against closely related genotypes HPV31/33/45. Impact estimates within the context of national HPV immunization programmes corroborate the vaccine and non-vaccine genotype efficacy data derived from clinical trials. Protection against vaccine-incorporated genotypes is likely mediated by neutralizing antibodies, while the basis for cross-protection against non-vaccine genotypes is less certain.
Review available data on the specificity of the vaccine-induced cross-neutralizing antibody response in relation to cross-protective efficacy against non-vaccine genotypes.
The generation of cross-neutralizing antibodies is a common feature of HPV vaccination with a tendency for Cervarix® vaccinees to exhibit a broader response with greater magnitude than Gardasil® vaccinees. Although such antibodies constitute only a minor component of the antibody reservoir, they are nevertheless detectable in genital secretions of vaccinated individuals. Serum cross-neutralizing antibodies are detectable several years post-vaccination but display age- and dose-dependencies. Emerging evidence suggests that some naturally occurring HPV variants maybe differentially sensitive to vaccine-induced cross-neutralizing antibodies.
These observations do not in themselves establish cross-neutralizing antibodies as correlates of cross-protection but suggest such antibodies may be used as surrogates. The broader vaccine-type protection afforded by second generation HPV vaccines will likely overshadow any benefit due cross-protection, but there will remain large cohorts of vaccinated women worldwide for which cross-protection will continue to play a significant role.