One gap in our understanding of the biology of HPV infection is that it is not known if infection with an HPV type confers immunity to subsequent reinfection with the same type. The availability of sensitive and specific serological assays using virus-like particles (VLPs) composed of HPV capsid proteins now makes it possible to address this issue. Studies to determine whether anti-capsid protein antibodies will prevent infection in human populations would have relevance for efforts to develop VLP-based vaccines and may provide an estimate of the level of anti-capsid antibody that a vaccine would have to induce in order to be protective. We recently obtained permission to test serum specimens from women enrolled in three large prospective studies of the natural history of HPV infection; the CDC sponsored HERS, the NIH sponsored WIHS, and the NCI sponsored Guanacaste Project in Costa Rica. The former two studies include HIV positive and HIV negative women. Because HIV infected individuals may be a prime target population for an HPV vaccine, it is important to know if the relationship of pre-existing anti-HPV antibodies to the risk of subsequent HPV infection for these women is the same or different from that for HIV negative women. Recruitment sera from women enrolled in three studies will be tested by ELISA for antibodies to VLPs of HPV-16, -31, -18, -45, -6, and -11. The antibody status at recruitment will be related to incident HPV infection and/or disease over a follow-up period of 4-7 years. The following are the questions to be addressed in this proposal: (1) Are serum antibodies to VLPs of a particular HPV type associated with a decreased frequency of incident infection with that HPV type? (2) Are serum antibodies to an HPV type associated with a decreased frequency of incident infection with genetically closely related types? (3) What is the minimum level of VLP antibodies that confers full protection? (4) Are serum antibodies to VLPs associated with reinfections characterized by a lower viral load, shorter duration of viral shedding and/or lower risk of cytological abnormalities than that of incident infections in antibody negative women? (5) Are serum antibodies to HPV VLPs in HIV seropositive women, as compared to HIV seronegative women, associated with the same or a higher frequency of incident HPV infection and/or disease? (6) In HIV seropositive women, is the extent of immunodeficiency, as measured by CD4+ cell counts, inversely correlated with the degree of protection provided by pre-existing anti-VLP antibodies?
