Comparative humoral and cellular immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18–45 years: Follow-up through Month 48 in a Phase III randomized study

Abstract

Abbreviations: ANOVA, analysis of variance; AS04, Adjuvant System containing 3-O-desacyl-4'-monophosphoryl lipid A (MPL; 50 mg) adsorbed on aluminum salt (500 mg Al(OH) 3 ); ATP, according-to-protocol; CI, confidence interval; CMI, cell-mediated immune; CVS, cervicovaginal secretion; ED 50 , effective dose producing 50% response; ELISA, enzyme-linked immunosorbent assay; GM, geometric mean; GMR, geometric mean (titer) ratio; GMT, geometric mean titer; HPA, Health Protection Agency; HPV, human papillomavirus; IgG, immunoglobulin G; MSC, medically significant condition; nAb(s), neutralizing antibody(ies); NOAD, new onset autoimmune disease; NOCD, new onset chronic disease; PBMC, peripheral blood mononuclear cells; PBNA, pseudovirion-based neutralization assay; SAE, serious adverse event; TVC, total vaccinated cohort; VLP, virus-like particle.We previously reported higher anti-HPV-16 and -18 immune responses induced by HPV-16/18 vaccine compared with HPV-6/11/16/18 vaccine at Month 7 (one month after completion of full vaccination series) in women aged 18-45 y in an observer-blind study NCT00423046; the differences of immune response magnitudes were maintained up to Month 24. Here we report follow-up data through Month 48. At Month 48, in according-to-protocol cohort for immunogenicity (seronegative and DNA-negative for HPV type analyzed at baseline), geometric mean titers of serum neutralizing antibodies were 2.0-to 5.2-fold higher (HPV-16) and 8.6-to 12.8-fold higher (HPV-18) in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. The majority of women in both vaccine groups remained seropositive for HPV-16. The same trend was observed for HPV-18 in HPV-16/18 vaccine group; however, seropositivity rates in HPV-6/ 11/16/18 vaccine group decreased considerably, particularly in the older age groups. In the total vaccinated cohort (regardless of baseline serological and HPV-DNA status), anti-HPV-16 and -18 neutralizing antibody levels induced by HPV-16/18 vaccine were higher than those induced by HPV-6/11/16/18 vaccine. CD4C T-cell response for HPV-16 and HPV-18 was higher in HPV-16/18 vaccine group than in HPV-6/11/16/18 vaccine group. Memory B-cell responses appeared similar between vaccine groups. Both vaccines were generally well tolerated. Overall, the higher immune response observed with the HPV-16/18 vaccine was maintained up to Month 48. A head-to-head study incorporating clinical endpoints would be required to confirm whether the observed differences in immune response between the vaccines influence the duration of protection they provided.

Immunogenicity and protective efficacy of an EV71 virus-like particle vaccine against lethal challenge in newborn mice

“…Combing the content of antigen and other control standard to detect the different lots vaccine of ED 50 , which could received the consistency data of vaccines quality. [42][43][44] In our paper we calculated the ED 50 of the EV71 VLPs and the anti-EV71 serum. It may predict the protective efficacy in humans when compared with future clinical trial results and could be instructive to determine the dosage used in future clinical trials.…”

Comparison of long-term immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and HPV-6/11/16/18 vaccine in healthy women aged 18-45 years: End-of-study analysis of a Phase III randomized trial

“…2 The observed differences in the magnitude of immune responses between the vaccines were maintained at Month 24 3 and up to Month 48. 4 This study is now complete and data on vaccine-induced antibody responses up to 5 y postvaccination (Month 60) are presented.…”

Cost-effectiveness of two-dose human papillomavirus vaccination in Singapore

“…(58)(59)(60) Differences in the magnitude of immune response between vaccines have been suggested to determine the duration of protection, although such differences are not accounted for in the current model. (59) (33) Due to the lack of published HPV-related disutility weights for the Singaporean population, disutility weights for pre-malignant stages and cervical cancer stages from other countries were applied. Disutilities were assumed to be constant over time and they were subtracted from a utility value of 1 for all ages.…”