HPV vaccination in HIV+ adolescents and young adults induces strong HPV-specific immune responses

Abstract

Background: HPV-associated ano-genital infections represent the most common sexually-transmitted disease in the general population. The incidence of HPV-associated cancers has been increasing in HIV-infected patients. HPV vaccination may be an approach to reduce the risk of HPVassociated cancers in HIV-infected patients and a combined strategy of screening and vaccination may guarantee an adequate prevention of HPVassociated lesions. Immunogenicity of HPV vaccines in HIV-infected patients is still not adequately evaluated. We analyzed immunogenicity of a quadrivalent HPV vaccine in HIV-infected patients without molecular evidence of vaccine-type HPV infection focusing on HPV-specific cell mediated immunity (CMI). Methodology: 31 ARV-treated HIV-infected adolescents (age range 28-14 years, with undetectable viremia and effective CD4 recovery) and 25 sexand age-matched HIV-seronegative healthy controls were enrolled in the study. HPV-16/18/6/11 VLP vaccine (Gardasil®) was administered 3 times (baseline, 2 and 6 months). Immune activation (CD4/CD25/HLADRII, CD8/ CD25/HLADRII), T-cell patterns and HPV-specific immune responses (CD4/ IFN-g/IL-2, CD8/IFN-g/TNF-a, CD8/Perforin/GranzymeB) were evaluated. Results: HIV-infected individuals showed: 1) no changes in CD4 counts, percentage of CD4 cells and HIV viral load; 2) a significant increase in naïve CD8 T-cells, activated CD8 T-cells and in central memory CD4 and CD8 T-cells; 3) a significant reduction in terminally differentiated CD8 T-cells; 4) a significant increase in unstimulated and in HPV-specific IL2+/CD4+, IFN-g +/CD4+, IFN-g+/CD8+ and TNF-a+/CD8+ T-cells; and 5) a significant increase in HPV-specific Perforin- and Granzyme B-secreting CD8 T-cells. Results obtained in HIV-infected patients were comparable to those seen in HC. Conclusions: HPV-16/18/6/11 VLP vaccine induces strong HPV-specific cell-mediated immunity in ARV-treated HIV-infected individuals that are comparable to those observed in HIV-seronegative controls. HPV-specific CMI is likely an important component of the protective effect of this vaccine, data herein indicating that this arm of immunity is not impaired in ARV-treated HIV infected individuals.