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

Abstract

This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12-13 year-old girls who were vaccinated at the age of 9-10 with 2 doses of qHPV (0-6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99-100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88-98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93-99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4-1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.

HPV vaccines – A review of the first decade

“…Canada trialed a two dose, six month interval, Gardasil vaccination series followed by a booster three years after initial vaccination in girls 9-10 years old [19]. The booster was randomized to either Cervarix or Gardasil.…”

Alternative HPV vaccination schedules in Latin America

“…Thus, a three-dose vaccine regimen over six months was originally chosen for HPV vaccines copying the Hepatitis B vaccine schedule (0, 1-2, 6 months). Alternative vaccine schedules have been proposed afterwards based in: i) noninferior immunogenicity or immune response levels compared to those at which clinical efficacy has been proven (i.e., those observed in a 3-dose vaccine schedule in women aged [15][16][17][18][19][20][21][22][23][24][25][26]; and, ii) proven efficacy in clinical trials and/ or effectiveness among women who were provided less than three doses due to a lack of adherence to a 3-dose vaccine schedule. In 2007, the Comité sur l'Immunisation du Québec published a report containing the initial arguments, both immunological and operational, for an extended HPV vaccination schedule at months 0, 6 and 60.…”

“…As the immune response was only assessed one month post-booster given at 18-36 months post-second dose when an antibody plateau is expected, long-term data are needed to further evaluate the effect and persistence of immunity after a booster dose. 17 The information above was subsequently used in 2009 by an External Assessment Committee established for advising on the introduction of HPV immunization in Mexico. The Committee recommended vaccination with a 0-6-60 months schedule based on the facts above and the additional benefits of its application: simplified logistics and infrastructure, higher coverage using the same amount of resources and potential combined strategy of third dose administration at sexual debut ages within a sexual education intervention.…”

Personalized Human Papillomavirus Vaccination for Persistence of Immunity for Cervical Cancer Prevention: A Critical Review With Experts' Opinions

“…The goal of vaccination is to provide a life-time persistence of specific antibodies against HPV infection, primarily because the effectiveness and acceptability of the HPV vaccine would be greatly improved if the protection were sustained, without the need for repeated boosting throughout life. Currently, long-term follow-up studies evaluating increased effects of the booster doses of HPV vaccine are limited (12). There are a number of approaches to improve vaccine effectiveness: On the one hand, vaccine adjuvants, which facilitate increased and longer-lasting immunity in vaccines are crucial for the effectiveness of the HPV vaccine persistence of immunity (POI) (11,13).…”