Impact of baseline covariates on the immunogenicity of a quadrivalent (types 6, 11, 16, and 18) human papillomavirus virus-like-particle vaccine.

BACKGROUND: The quadrivalent (types 6, 11, 16, and 18) human papillomavirus (HPV) L1 virus-like-particle vaccine was 95%-100% effective in preventing cervical and genital disease related to HPV-6, -11, -16, and -18. Vaccine efficacy is thought to be mediated by humoral immunity. Here, we analyze the effect of the baseline characteristics of subjects on vaccine-induced immune responses. METHODS: Immunogenicity data from 12,343 subjects 9-26 years old randomized to quadrivalent HPV vaccine or placebo in phase 2/3 studies were analyzed. Covariates examined were day 1 HPV serostatus, age, race/ethnicity, region of residence, lactation status, hormonal contraceptive usage, smoking status, Pap test diagnosis, immunosuppressant or anti-inflammatory agent use, and number of sex partners. Anti-HPV responses were summarized as serum anti-HPV-6, -11, -16, or -18 geometric mean titers 1 month after dose 3. RESULTS: Age at vaccination initiation was inversely proportional to the vaccine-induced anti-HPV response. Vaccination of subpopulations of subjects who were seropositive at day 1 to a vaccine HPV type resulted in more robust anti-HPV responses to that type, compared with those in subjects who were seronegative at baseline. Anti-HPV responses were comparable among the remaining demographic subgroups. CONCLUSIONS: The immunogenicity of quadrivalent HPV vaccine was comparable among subjects with differing baseline characteristics. These data support vaccination with quadrivalent HPV vaccine across a broad range of baseline subject characteristics.

Induction of immune memory following administration of a prophylactic quadrivalent human papillomavirus (HPV) types 6/11/16/18 L1 virus-like particle (VLP) vaccine.

BACKGROUND: The duration of protection afforded by vaccines represents a critical test of their utility as public health interventions. Some vaccines induce long-term immunity, while others require booster doses. Vaccines that induce long-term protection are usually characterized by the generation of immune memory. Recent trials of a quadrivalent (types 6, 11, 16, 18) human papillomavirus (HPV) vaccine have demonstrated high efficacy through 5 years of follow-up. We evaluated the extent to which the vaccine is able to generate HPV type-specific immune memory. METHODS: A total of 552, 16-23-year-old women were enrolled in a double-blind, placebo-controlled study. At enrollment, subjects were randomized in a 1:1 ratio to receive three-dose regimens of quadrivalent HPV vaccine or placebo with 3 years' follow-up. A subset of 241 subjects (n=114 in the quadrivalent HPV vaccine group and n=127 in the placebo group) underwent 2 further years of follow-up. All extension subjects received quadrivalent HPV vaccine at month 60 to examine the extent of immune memory in response to the primary vaccination series. RESULTS: Serum anti-HPV levels declined post-vaccination, but reached a plateau at month 24 that remained stable through month 60. Administration of a challenge dose of vaccine induced a classic anamnestic response, with anti-HPV levels 1 week post-challenge reaching levels observed 1 month following the completion of the three-dose primary series. At 1 month post-challenge, anti-HPV responses were higher than those observed 1-month post-dose 3. DISCUSSION: A three-dose regimen of quadrivalent HPV vaccine induces high efficacy and stable anti-HPV levels for at least 5 years. Vaccination also induces robust immune memory. These findings suggest that the efficacy of this vaccine will be long lasting.

Noninferiority of antibody response to human papillomavirus type 16 in subjects vaccinated with monovalent and quadrivalent L1 virus-like particle vaccines.

The incorporation of multiple antigens into a single human papillomavirus (HPV) vaccine may induce immune interference. To evaluate whether interference occurs when HPV type 16 (HPV16) virus-like particles are combined in a multivalent vaccine, we conducted a study to evaluate anti-HPV16 responses among subjects receiving three-dose regimens of either a monovalent HPV16 vaccine or a quadrivalent HPV (types 6, 11, 16, and 18) vaccine.