HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy

Humanpapillomavirus(HPV)persistentinfectionsareassociatedwithcervicalcancerandother HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently availableHPVvaccinesisimportant. Atotalof149femalesubjectsvaccinatedwithCervarixorGardasil participatedtothestudyandtheywerestratifiedaccordingtoage(10–12-year-oldand16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memoryBcellswereanalyzedafteranaverageof4–6yearsfromthethirdimmunization. Thehumoral responses against HPV-16 and HPV-18 (andHPV-6andHPV-11forGardasil) were high in both age groupsandvaccinesuptosixyearsfromthethirddose. However,Cervarixinducedsignificantlyhigher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memoryBcellsagainstHPV-16andHPV-18. Moreover,thepercentageofsubjectswithvaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individualswithcirculatingantibodies,butundetectablememoryBcellswerefound. Finally,ahigher proportionofCervarix-vaccinatedsubjectsdisplayedcross-neutralizingresponsesagainstnon-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differe