Cross-sectional study on the prevalence of HPV antibodies in the general population of the Czech Republic.

OBJECTIVES: The assessment of the prevalence of antibodies to human papillomaviruses (HPV) in the healthy population is essential for effective planning of HPV vaccine implementation into the preventive programmes for HPV-associated diseases and for the prospective monitoring of the impact of HPV vaccines in the Czech population. METHODS: The seropositivity for HPV-6, 11, 16, 18, 31 and 33 virus-like particles was determined in sera from 3150 healthy individuals (age range 6-76 years) by means of enzyme-linked immunoassay. RESULTS: The seroprevalences for HPV-6, 11, 16, 18, 31 and 33 were 23.8%, 15.2%, 14.5%, 9.9%, 16.4% and 9.6% in women and 18.4%, 13.7%, 6.5%, 5.4%, 6.1% and 4.3% in men. For both genders, except for HPV11, these rates were age dependent. The prevalence of antibodies to HPV-16 and/or 18 reached the maximum of 27.0% in women 30-39 years of age and of 14.4% in men 50-59 years of age. The highest proportion of individuals' seropositive for any of the vaccine types HPV-6/11/16/18 was in 30- to 39-year-old women (50.0%) and in ≥ 60-year-old men (37.6%). Antibodies specific for vaccine HPV types were detected in 18.0% of children 6- to 14-year-old but in 26.4%, those older than 14 years. CONCLUSIONS: The data reveal age-specific differences in the HPV seropositivity rates between healthy women and men and support the implementation of HPV vaccination in the Czech Republic before the age of 13.

Prime/boost immunotherapy of HPV16-induced tumors with E7 protein delivered by Bordetella adenylate cyclase and modified vaccinia virus Ankara.

The Bordetella adenylate cyclase toxoid (CyaA) targets cells expressing the alphaMbeta2 integrin receptor CD11b/CD18 (CR3 or Mac-1) and can penetrate into cytosol of professional antigen-presenting cells, such as dendritic cells. This allows us to use CyaA for delivery of passenger antigens into the cytosolic pathway of processing and MHC class I-restricted presentation, which can promote induction of antigen-specific CD8+ cytotoxic T-lymphocyte immune responses. We show here that vaccination with a genetically detoxified CyaA336/E7 protein, carrying the full-length oncoprotein E7 of the human papilloma virus 16 inserted at position 336 of the cell-invasive AC domain of CyaA, induces an E7-specific CD8+ T-cell immune response and confers on mice protective, as well as therapeutic immunity against challenge with TC-1 tumor cells expressing the E7 oncoprotein. The therapeutic efficacy of priming with the CyaA336/E7 vaccine could further be enhanced by a heterologous booster immunization with a highly attenuated modified vaccinia virus Ankara (MVA) expressing the E7 protein fused to the lysosome-associated membrane protein (LAMP1). These results establish the potential of CyaA as a new antigen delivery tool for prime/boost immunotherapy of tumors.