Immunogenicity of quadrivalent HPV and combined hepatitis A and B vaccine when co-administered or administered one month apart to 9–10 year-old girls according to 0–6 month schedule

Abstract

IntroductionThe approved schedules for human papilloma virus (HPV) vaccines (qHPV (Gardasil®) and bHPV (Cervarix®)) include three doses administered at 0, 1-2 and 6 m. The first two doses given within a relatively short period of time are expected to prime the immune system and the third is expected to confer long-lasting immunity.1 When given according to this schedule to 16-45 y old females, HPV vaccines have been shown to be highly immunogenic and protect against persistent infection, anogenital warts and precancerous abnormalities.2-10 Post-licensure trials with bHPV showed that > 98% of 15-25 y old females developed antibodies to HPV 16 and HPV 18 which remain detectable up to 76 mo after a single vaccine dose.3 In addition, a significant increase in antibody titers resulted from a second dose of vaccine and high clinical efficacy was demonstrated in individuals who received less than three vaccine doses. [4][5][6] Finally, in preadolescents and adolescents, both HPV and combined HAV/HBV vaccines Background. No immunogenicity data has been reported after a single dose of the quadrivalent HPV vaccine (qHPVGardasil®) and no data are available on co-administration of this vaccine with the HAV/HBV vaccine (Twinrix-Junior®). Two pre-licensure studies reported similar anti-HPV but lower anti-HBs titers when co-administering HPV and HBV vaccines.Objectives. To assess the immunogenicity of the qHPV and HAV/HBV vaccine when co-administered (Group-co-adm) or given one month apart (Group-sep) and to measure the persistence of HPV antibodies three years post-second dose of qHPV vaccine in both study groups.Methods. 416 9-10 year-old girls were enrolled. Vaccination schedule was 0-6 months. Anti-HAV and anti-HBs were measured in all subjects 6 months post-first dose and 1 month post-second dose. Anti-HPV were measured 6 months post-first dose in Group-co-adm and in all subjects 1 and 36 months post-second dose.Results. six months post-first dose: 100% of subjects had detectable anti-HAV and 56% and 73% had detectable antiHBs in Group-co-Adm and Group-sep, respectively. In Group-co-adm 94, 100, 99 and 96% had detectable antibodies to HPV 6, 11, 16 and 18, respectively. One month post-second dose of qHPV and HAV/HBV vaccine, in both study groups 99.5-100% of subjects had an anti-HAV titer ≥ 20IU/L, 97.5-97.6% an anti-HBs level ≥ 10IU/L, and 100% had an anti-HPV titer ≥ 3LU. Thirty-six months post-second dose of qHPV all but four subjects (99%) had antibodies to HPV18 and 100% had antibodies to HPV6, 11 and 16. The great majority (97-100%) had an anti-HPV titer ≥ 3 LU. Post-second dose administration of qHPV and HAV/HBV, no meaningful difference was observed in the immune response in the two study groups to any component of vaccines.conclusions. The results indicate that qHPV and HAV/HBV can be given during the same vaccination session. Two doses of of qHPV and HAV/HBV vaccines induce a strong immune response. Three years post-second dose of qHPV, the great majority of subjects had antibodies to HPV types included in the v...

The effect of a booster dose of quadrivalent or bivalent HPV vaccine when administered to girls previously vaccinated with two doses of quadrivalent HPV vaccine

“…Thus, it is highly plausible that no different persistence of immunity or response to a booster dose would occur in non-participating subjects. Second, as previously reported 10 we used relatively strict enrollment criteria in 2008-2009 and immunogenicity results presented here should not be extrapolated to individuals with underlying comorbidities, especially to the immunocompromised individuals. Third, we did not measure the antibody avidity or cellular immune response and cannot exclude some differences in the 2 study groups.…”

“…We have previously reported the immunogenicity results when using qHPV (quadrivalent vaccine Gardasil Ò contains HPV6, HPV11, HPV16 and HPV18) according to a 0-6 month schedule in 9-10 year-old girls. 10 The results showed that 6 months post-first dose 94-100% of vaccinated girls have detectable antibodies to 4 HPV genotypes included in the vaccine and a 55-99-fold increase in antibody titers was observed post-second dose administration. However, little data on persistence of immunity exist when using qHPV in a 2-dose schedule and no data has been reported about the magnitude of the immune response to a booster third dose of vaccine when given a few years post-second dose.…”

“…Subjects' socio-demographic characteristics and immunogenicity and safety results post-first and post-second dose were reported elsewhere. 10,12 In 2011-2012 subjects were 12-13 year-old. Those who accepted to continue their participation were randomized 1:1 (SAS Institute software) to receive either a dose of qHPV (Group qHPV) or a dose of bHPV (Group bHPV).…”

“…4,5 In pre-licensure clinical trials conducted by vaccine manufacturers, the 0, 1-2 and 6 months schedule was used 4,5 and only a few post-licensure clinical trials assessed the immunogenicity and efficacy of alternative vaccination schedules including a 0, 6 month schedule in 9-13 year-old girls. [6][7][8][9][10] Existing data show that 2 doses of HPV vaccine administered to pre-adolescents induce an immune response which is similar to and even higher than the immune response observed after 3 doses given to [16][17][18][19][20][21][22][23][24][25][26] year-old females. 11 These observations raised the question regarding the number of doses needed when vaccinating pre-adolescent girls.…”

Less than 3 doses of the HPV vaccine – Review of efficacy against virological and disease end points

“…At six months after a single dose of the vaccine, 94-100% of the 9-10 y old girls had detectable antibodies in randomized controlled trials. 13 The originally recommended schedule of the HPV vaccines was to administer 2 priming doses (at one or 2 months interval) and a single booster dose at 6 months. A single priming dose is likely to be adequate for such a vigorously immunogenic vaccine, especially in adolescent populations with high immunecompetence.…”