Immunogenicity And Immunopersistence Of A Bivalent Human Papillomavirus Vaccine (E.coli) In A Female Population Aged 9-45 Years

Objectives:This study aims to analyze the immunogenicity and persistence of bivalent human papillomavirus vaccine(E.coli)(later referred to as "HPV vaccine",it was the first domestic HPV vaccine to be approved for marketing)in healthy women aged 9-45 years,and to provide a theoretical basis for the application of HPV vaccine.Methods:This study was based on a retrospective analysis of completed phase Ⅲclinical trials and immune bridging trials of HPV vaccine.725 girls aged 9-17 years and 3415 adult females aged 18-45 years were enrolled according to "full vaccination,no major protocol violations,and validated serologic results at 0d and 7m".The effect of age,immunization interval,baseline natural infection status,and vaccine lots on the immunogenicity of HPV vaccine were analysed by comparing seropositivity,seroconversion rate and geometric mean concentration(GMC),and on this basis,the persistence of HPV vaccine immunity was analysed,with a statistical description of antibody responses 2 years after vaccination in girls aged 9-17 years and 5 years after vaccination in adult women aged 18-45 years.Results:Seven months after the first dose of HPV vaccine,the peak level of vaccineinduced immunity was reached,and the seropositivity and seroconversion rates of HPV16/18 IgG antibodies in healthy women aged 9-45 years were close to 100%,with vaccine-induced HPV-16/18 IgG antibody GMCs of 886.6 IU/mL and 296.5 IU/mL,respectively.Among women aged 9-45 years who received 3 doses of HPV vaccine,all HPV 16/18 IgG antibody GMC decreased with age(P<0.05);deviations from the initial immunization interval(first and second dose)of 28-60 d and the booster interval(second and third dose)of 98-198 d had no significant effect on the immunogenicity of HPV vaccine.For people with different baseline DNA/antibody status,only HPV-16 was found to have higher vaccine immunogenicity in the baseline IgG antibody-negative and DNAnegative groups than in the corresponding positive groups in the 18-45 years(3-dose group);no statistical differences were found in the other groups.However,vaccineinduced HPV-16/18 IgG GMC was more than 100 and 50 times higher than natural infection in both the baseline DNA and antibody-positive and negative groups,respectively;differences in immunogenicity between vaccine lots were not statistically significant.At 2 years post-immunization,the seropositivity rate for HPV-16/18 IgG antibodies remained 100%in females aged 9-17 years,with HPV16 IgG GMC of 73.2 IU/mL,139.3 IU/mL,and 98.6 IU/mL,and HPV-18 IgG GMC were 24.9 IU/mL,71.2 IU/mL and 41.5 IU/mL in females aged 9-14 years(2-dose group),9-14 years(3-dose group),and 15-17 years(3-dose group);The seropositivity rate for HPV-16/18 IgG antibodies in women aged 18-45 years at 5 years post-immunization was close to 100%,with HPV16 IgG GMC of 51.7 IU/mL and 34.3 IU/mL,and HPV-18 IgG GMC of 19.3 IU/mL and 12.7 IU/mL in women aged 18-26 years(3-dose group)and 27-45 years(3-dose group),respectively.Conclusion:The bivalent human papillomavirus vaccine(E.coli)has good immunogenicity and persistence of immunity in a population of Chinese women aged 945 years,and the younger the age,the more immunogenic the HPV vaccine is.Postvaccination antibody levels were much higher than natural infection,regardless of prevaccination HPV-16/18 infection.For those who were unable to complete HPV vaccination on time,completion of three doses of HPV vaccine at intervals of 28-60 days for initial immunisation and 98-198 days for booster immunisation had no significant effect on the immune response.The study vaccine had stable lot-to-lot consistency and was of reliable product quality.5 years after HPV vaccination,high and stable levels of antibodies are still present and are expected to provide prolonged immune protection.