HPV vaccine: an overview of immune response, clinical protection, and new approaches for the future

Although long-term protection is a key-point in evaluating HPV-vaccine over time, there is currently inadequate information on the duration of HPV vaccine-induced immunity and on the mechanisms related to the activation of immune-memory. Longer-term surveillance in a vaccinated population is needed to identify waning immunity, evaluating any requirements for booster immunizations to assess vaccine efficacy against HPV-diseases. Current prophylactic vaccines have the primary end-points to protect against HPV-16 and 18, the genotypes more associated to cervical cancer worldwide. Nevertheless, data from many countries demonstrate the presence, at significant levels, of HPVs that are not included in the currently available vaccine preparations, indicating that these vaccines could be less effective in a particular area of the world. The development of vaccines covering a larger number of HPVs presents the most complex challenge for the future. Therefore, long term immunization and cross-protection of HPV vaccines will be discussed in light of new approaches for the future

Rectal and vaginal immunization of mice with human papillomavirus L1 virus-like particles.

Human papillomavirus (HPV) vaccines based on L1 virus-like particle (VLP) can prevent genital HPV infection and associated lesions after three intramuscular injections. Needle-free administration might facilitate vaccine implementation, especially in developing countries. Here we have investigated rectal and vaginal administration of HPV16 L1 VLPs in mice and their ability to induce anti-VLP and HPV16-neutralizing antibodies in serum and in genital, rectal and oral secretions. Rectal and vaginal immunizations were not effective in the absence of adjuvant. Cholera toxin was able to enhance systemic and mucosal anti-VLPs responses after rectal immunization, but not after vaginal immunization. Rectal immunization with Resiquimod and to a lesser extent Imiquimod, but not monophosphoryl lipid A, induced anti-HPV16 VLP antibodies in serum and secretions. Vaginal immunization was immunogenic only if administered in mice treated with nonoxynol-9, a disrupter of the cervico-vaginal epithelium. Our findings show that rectal and vaginal administration of VLPs can induce significant HPV16-neutralizing antibody levels in secretions, despite the fact that low titers are induced in serum. Imidazoquinolines, largely used to treat genital and anal warts, and nonoxonol-9, used as genital microbicide/spermicide were identified as adjuvants that could be safely used by the rectal or vaginal route, respectively