Abstract
Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view.
Highlights
Human papillomavirus (HPV) infection is the most frequent sexually transmitted viral infection, which is associated with the occurrence of both benign and malignant lesions
Cervarix ensures the long-term duration of humoral responses against both HPV-16 and HPV-18 in all adolescents (10–12 y individuals) and in more than 90% of young adults (16–20 y individuals), whereas the percentages of subjects with detectable IgG titers is lower in Gardasil-vaccinated women, in young adults for HPV-18 specific-IgG
These results indicate that Cervarix induces long-lasting humoral immunity in both adolescents and young adult women against HPV-16 and HPV-18 subtypes
Summary
Human papillomavirus (HPV) infection is the most frequent sexually transmitted viral infection, which is associated with the occurrence of both benign and malignant lesions. Persistent infection with high-risk HPV types is the fourth major cause of cervical cancer worldwide and it is associated with ano-genital and oropharynx cancers, in both males and females, in a time frame of 15–20 years after acquisition or even less (5–10 years) in persons with a weakened immune system. A vaccine that induces long-term immune responses and protection against oncogenic HPV types is of outmost importance in preventing cervical cancer and other HPV-related diseases and tumours. All of the vaccines elicit high titres of potent, type-specific nAbs that prevent infection by transudation or exudation through the epithelium at the site of infection [8,18,19] and induce protection against cervical cancer that is associated to the vaccine HPV with approximately 100% efficacy [20,21,22,23]. As the role of memory B cells is not completely clear in the case of HPV vaccination, we measured their persistence in comparison to antibody levels and properties
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