Immunogenicity And Safety Of An E.Coli-produced Bivalent Humanpapillomavirus(Type 16 And 18) Vaccine In Preadolescent Girls Of 9-17 Years

Objectives:To evaluate the immunogenicity and safety of an Escherichia Coli produced bivalent human papillomavirus(type 16 and 18)vaccine administered in girls aged 9-17 years.Method:Participants were enrolled afer signing the informed consent and met the inclusion criterias but not the exclusion ones.This is an open label designed immunogenicity and safety study.Subjects of 9-14 years old were randomly assinged to the standard 0/1/6 month schedule or the alternative 0/6 month schedule,while all subjects of 15-26 years old the standard one.Participants would receive one dose vaccine each visit during specific time window.After injection all reactions occured in 1 month after injecion were required to be recorded on the dinary card.Blood samples were collected at 0,6,7 month to evaluate the immune response to detect the IgG antibody and the nuetrolizing antibody of vaccine related HPV type.Results:1031 subjects from Yancheng city in Jiangsu province were recurited during the october of 2015.979 participants were entrolled and 934 got the qualified blood sample detected.In per-protocol and intention-to treat dataset the immune response of the 9-14 years of 3 dose was demostrated to be noninferior to the 18-26 years of 3 dose with the HPV 16,18 geometric mean concentration ratio being 1.70,1.89 above.The same conclusion could be draw from the 9-14 years of 2 dose compared with the 18-26 years with the ratio being 1.32,1.21 above.The assumption of non-inferiority between 9-14 years of 2 dose and 9-14 years of 3 dose was not supported and the ratio was aroud 0.67-0.70,0.45-0.61 seperately.The differences of seroconversion were all above 0.00%with the lower bound of 95%CI above-5%.The administration of the Escherichia Coli produced HPV 16/18 vaccine was tolerated in preadolesenct girls.The rate of total adverse events was similar in participants of 9-14 years of 2 dose,9-14 years of 3 dose,9-17 years of 3 dose,28-26 years of 3 dose with the rate around 67%-80%.The systemic adverse event occuring in the four groups were around 54%-63%.The most six common systemic adverse events were pain at injection site,fever,cough,fatigue,swelling at injection site.The distribution of severity,association in the total adverse event is similiar with 79.92%being grade 1 and 55.47%related to vaccination.Seriou adverse event was rare,and the rate was 0.31%.Conclusions:1)Immunogenicity induced by the Escherichia Coli produced humanpapillomavirus vaccine in girls aged 9-17 years is non-inferior as compared to 18-26 women when administered accroding to the standard 0/1/6 monthe schedule.2)Immunogenicity induced by the candidate vaccine in girls of 9-14 years receiving 2 doses with six months interval is non-inferior as compared to 18-26 women receiving 3 doses.3)Immunogenicity induced by the candidate vaccine in girls of 9-14 years receiving 2 doses with six months interval is not supported to be non-inferior as compared to grils of 9-14 years receiving 3 doses.4)The candidate vaccine was tolerated in girls aged 9-17 years.