Mucosal but not parenteral immunization with purified human papillomavirustype 16 virus-like particles induces neutralizing titers of antibodies throughout the estrous cycle of mice

We have recently shown that nasal immunization of anesthetized mice with hu man papillomavirus type 16 (HPV16) virus-like particles (VLPs) is highly ef fective at inducing both neutralizing immunoglobulin A (IgA) and IgG in gen ital secretions, while parenteral immunization induced only neutralizing Ig G. Our data also demonstrated that both isotypes are similarly neutralizing according to an in vitro pseudotyped neutralization assay. However, it is known that various amounts of IgA and IgG are produced in genital secretion s along the estrous cycle. Therefore, we have investigated how this variati on influences the amount of HPV16 neutralizing antibodies induced after imm unization with VLPs. We have compared parenteral and nasal protocols of vac cination with daily samplings of genital secretions of mice. Enzyme-linked immunosorbent assay analysis showed that total IgA and IgG inversely varied along the estrous cycle, with the largest amounts of IgA in proestrus-estr us and the largest amount of IgG in diestrus. This resulted in HPV16 neutra lizing titers of IgG only being achieved during diestrus upon parenteral im munization. In contrast, nasal vaccination induced neutralizing titers of I gA plus IgG throughout the estrous cycle, as confirmed by in vitro pseudoty ped neutralization assays. Our data suggest that mucosal immunization might be more efficient than parenteral immunization at inducing continuous prot ection of the female genital tract.