Safety and immunogenicity of a quadrivalent human papillomavirus (types 6, 11, 16, and 18) vaccine in HIV-infected children 7 to 12 years old.

BACKGROUND: Quadrivalent human papillomavirus vaccine (QHPV) is > 95% effective in preventing infection with vaccine-type human papillomavirus. The safety and immunogenicity of QHPV are unknown in HIV-infected children. METHODS: HIV-infected children (N = 126)-age > 7 to < 12 years, with a CD4% ≥ 15-and on stable antiretroviral therapy if CD4% was < 25-were blindly assigned to receive a dose of QHPV or placebo (3:1 ratio) at 0, 8, and 24 weeks. Adverse events were evaluated after each dose. Serum antibody against QHPV antigens was measured by a competitive Luminex immunoassay 1 month after the third QHPV dose. RESULTS: The safety profile of QHPV was similar in the 2 study arms and to that previously reported for QHPV recipients. QHPV did not alter the CD4% or plasma HIV RNA. Seroconversion to all 4 antigens occurred in > 96% of QHPV recipients and in no placebo recipients. Geometric mean titer was > 27 to 262 times greater than the seropositivity cutoff value, depending on the antigen, but was 30%-50% lower against types 6 and 18 than those of age-similar historical controls. CONCLUSIONS: QHPV was safe and immunogenic in this cohort of HIV-infected children. Efficacy trials are warranted.

Impact of a quadrivalent HPV6/11/16/18 vaccine in Mexican women: public health implications for the region.

BACKGROUND AND AIMS: Recognition of human papillomavirus (HPV) as a necessary cause of cervical cancer (CC) led to new perspectives for its control and the demonstration of an effective primary prevention strategy through vaccination. We undertook this study to evaluate the safety, efficacy and immunogenicity of a quadrivalent HPV6/11/16/18 vaccine in Mexican women. METHODS: A total of 679 Mexican women between 18 and 23 years old participated in two Phase III double-blind, randomized, placebo-controlled clinical trials of a quadrivalent HPV 6/11/16/18 vaccine. Women were enrolled who tested negative for pregnancy and reported having four or less sexual partners during their lifetime. Vaccine or placebo was administered at day 1, month 2 and month 6. RESULTS: Among Mexican women who were naïve to the respective vaccine type at enrollment, the quadrivalent vaccine was highly efficacious, preventing 100% of HPV6/11/16/18-related cervical intraepithelial neoplasia grade 2/3, adenocarcinoma in situ, condyloma and vaginal intraepithelial neoplasia. Statistical significance was not reached for every endpoint due to the limited sample size. Vaccination was generally well tolerated and immunogenic. DISCUSSION: To widely administer the vaccine, collaborative efforts should be coordinated among public, private and local community sectors. In light of the scarce knowledge of many health professionals with respect to the primary prevention of CC, it will be necessary to educate health providers on the advantages and specific recommendations of HPV vaccines and secondary prevention. Decision making should be based on scientific evidence, allowing health professionals to provide an organized social response that supports the universal right to health.

Safety and immunogenicity of co-administered quadrivalent human papillomavirus (HPV)-6/11/16/18 L1 virus-like particle (VLP) and hepatitis B (HBV) vaccines.

Adolescents and young adults are at high risk for human papillomavirus (HPV) and hepatitis B virus (HBV) infections, which are preventable by currently available, safe and effective, prophylactic vaccines. However, development of a combined immunization strategy may lead to better compliance for these vaccines, thereby contributing to the overall goal of protection against these diseases. This study assessed the safety and immunogenicity of co-administered quadrivalent HPV-6/11/16/18 L1 VLP and HBV vaccines in women (n=1877) aged 16-23 years. Co-administration of HPV and HBV vaccines induced robust anti-HPV-6, HPV-11, HPV-16, HPV-18 geometric mean titers (GMTs) and > or =99% seroconversion rates (Month 7) that were both non-inferior (p<0.001) to those induced by HPV vaccine alone. High Month 7 anti-HBs GMTs were also observed following concomitant vaccination. These GMTs were lower compared to those induced by the HBV vaccine itself; however, >96% of subjects achieved an anti-HBs seroprotection level of > or =10 mIU/mL that was non-inferior (p<0.001) to that of HBV vaccine alone. Overall, co-administered and individual vaccines were generally well-tolerated and did not interfere with the immune response of either vaccine (ClinicalTrials.gov number, NCT00092521).

Safety, immunogenicity, and efficacy of quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like-particle vaccine in Latin American women.

The prevalence of HPV infection in Latin America is among the highest in the world. A quadrivalent (types 6/11/16/18) human papillomavirus L1 virus-like-particle vaccine has been shown to be 95-100% effective in preventing HPV 6/11/16/18-related cervical and genital disease in women naive to vaccine HPV types. A total of 6,004 female subjects aged 9-24 were recruited from Brazil, Mexico, Colombia, Costa Rica, Guatemala and Peru. Subjects were randomized to immunization with intramuscular (deltoid) injections of HPV vaccine or placebo at enrollment (day 1), month 2 and month 6. Among vaccinated subjects in the per-protocol population from Latin America, quadrivalent HPV vaccine was 92.8 and 100% effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types, respectively. These data support vaccination of adolescents and young adults in the region, which is expected to greatly reduce the burden of cervical and genital cancers, precancers and genital warts.

Quadrivalent vaccine against human papillomavirus to prevent anogenital diseases.

BACKGROUND: A phase 3 trial was conducted to evaluate the efficacy of a prophylactic quadrivalent vaccine in preventing anogenital diseases associated with human papillomavirus (HPV) types 6, 11, 16, and 18. METHODS: In this randomized, placebo-controlled, double-blind trial involving 5455 women between the ages of 16 and 24 years, we assigned 2723 women to receive vaccine and 2732 to receive placebo at day 1, month 2, and month 6. The coprimary composite end points were the incidence of genital warts, vulvar or vaginal intraepithelial neoplasia, or cancer and the incidence of cervical intraepithelial neoplasia, adenocarcinoma in situ, or cancer associated with HPV type 6, 11, 16, or 18. Data for the primary analysis were collected for a per-protocol susceptible population of women who had no virologic evidence of HPV type 6, 11, 16, or 18 through 1 month after administration of the third dose. RESULTS: The women were followed for an average of 3 years after administration of the first dose. In the per-protocol population, those followed for vulvar, vaginal, or perianal disease included 2261 women (83%) in the vaccine group and 2279 (83%) in the placebo group. Those followed for cervical disease included 2241 women (82%) in the vaccine group and 2258 (83%) in the placebo group. Vaccine efficacy was 100% for each of the coprimary end points. In an intention-to-treat analysis, including those with prevalent infection or disease caused by vaccine-type and non-vaccine-type HPV, vaccination reduced the rate of any vulvar or vaginal perianal lesions regardless of the causal HPV type by 34% (95% confidence interval [CI], 15 to 49), and the rate of cervical lesions regardless of the causal HPV type by 20% (95% CI, 8 to 31). CONCLUSIONS: The quadrivalent vaccine significantly reduced the incidence of HPV-associated anogenital diseases in young women. (ClinicalTrials.gov number, NCT00092521 [ClinicalTrials.gov].).

Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials.

BACKGROUND: Vulval and vaginal cancers among younger women are often related to infection with human papillomavirus (HPV). These cancers are preceded by high-grade vulval intraepithelial neoplasia (VIN2-3) and vaginal intraepithelial neoplasia (VaIN2-3). Our aim was to do a combined analysis of three randomised clinical trials to assess the effect of a prophylactic quadrivalent HPV vaccine on the incidence of these diseases. METHODS: 18 174 women (16-26 years) were enrolled and randomised to receive either quadrivalent HPV6/11/16/18 L1 virus-like-particle vaccine or placebo at day 1, and months 2 and 6. Individuals underwent detailed anogenital examination at day 1, 1 month after dose three, and at 6-12-month intervals for up to 48 months. Suspect genital lesions were biopsied and read by a panel of pathologists and vaccine HPV type-specific DNA testing was done. The primary endpoint was the combined incidence of VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. Primary efficacy analyses were done in a per-protocol population. FINDINGS: The mean follow-up time was 3 years. Among women naive to HPV16 or HPV18 through 1 month after dose three (per-protocol population; vaccine n=7811; placebo n=7785), the vaccine was 100% effective (95% CI 72-100) against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18. In the intention-to-treat population (which included 18 174 women who, at day 1, could have been infected with HPV16 or HPV18), vaccine efficacy against VIN2-3 or VaIN2-3 associated with HPV16 or HPV18 was 71% (37-88). The vaccine was 49% (18-69) effective against all VIN2-3 or VaIN2-3, irrespective of whether or not HPV DNA was detected in the lesion. The most common treatment-related adverse event was injection-site pain. INTERPRETATION: Prophylactic administration of quadrivalent HPV vaccine was effective in preventing high-grade vulval and vaginal lesions associated with HPV16 or HPV18 infection in women who were naive to these types before vaccination. With time, such vaccination could result in reduced rates of HPV-related vulval and vaginal cancers.

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.

Comparison of the immunogenicity and reactogenicity of a prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus-like particle vaccine in male and female adolescents and young adult women.

OBJECTIVE: Prophylactic vaccination of 16- to 23-year-old females with a quadrivalent human papillomavirus (types 6, 11, 16, 18) L1 virus-like particle vaccine has been shown to prevent type-specific human papillomavirus infection and associated clinical disease. We conducted a noninferiority immunogenicity study to bridge the efficacy findings in young women to preadolescent and adolescent girls and boys, who represent a primary target for human papillomavirus vaccination. METHODS: We enrolled 506 girls and 510 boys (10-15 years of age) and 513 females (16-23 years of age). Participants were vaccinated on day 1, at month 2, and at month 6, and serology testing was performed on day 1 and at months 3 and 7 on blinded samples. Neutralizing antibody concentrations were determined using type-specific immunoassays and summarized as geometric mean titers and seroconversion rates. Vaccine tolerability also was assessed. RESULTS: By month 7, seroconversion rates were > or = 99% for all 4 human papillomavirus types in each group. By month 7, compared with women, anti-human papilloma virus geometric mean titers in girls or boys were noninferior and were 1.7- to 2.7-fold higher. Most (> 97%) injection-site adverse events were mild to moderate in intensity. Significantly more boys (13.8%) and girls (12.8%) than women (7.3%) reported fevers > or = 37.8 degrees C within 5 days of vaccination. Most (96.4%) fevers were mild (< 39 degrees C). CONCLUSIONS: Noninferior immunogenic responses to all 4 human papillomavirus types in the quadrivalent vaccine permit the bridging of efficacy data that were generated in young women to girls. The results in boys lend support for the implementation of gender-neutral human papillomavirus vaccination programs. This vaccine generally was well tolerated.

Prospective comparison of risk factors and demographic and clinical characteristics of community-acquired, methicillin-resistant versus methicillin-susceptible Staphylococcus aureus infection in children.

CONTEXT: Community-acquired, methicillin-resistant (CA-MRSA) infections in children are increasing in frequency for unknown reasons. OBJECTIVES: To compare the presence of risk factors for methicillin resistance between patients with CA-MRSA and community-acquired methicillin-susceptible (CA-MSSA) infection and to compare the presence of risk factors among household contacts of the patients from both groups. To compare the demographic and clinical characteristics between children with CA-MRSA and CA-MSSA infection. DESIGN: Prospective observational study conducted between February 2, 2000 and November 14, 2000, excluding the month of May and the period between September 2 and October 15. SETTING AND PATIENTS: Texas Children's Hospital, Houston, TX; inpatients and outpatients with community-acquired infection. MAIN OUTCOME MEASURES: Proportion of MRSA among all community-acquired infections. The presence of risk factors associated with methicillin resistance among patients, and their household contacts, with CA-MRSA and CA-MSSA. RESULTS: The monthly rates of methicillin resistance of varied between 35 and 51%. CA-MSSA isolates were associated with deep-seated infections significantly more often (30%) than CA-MRSA isolates (11%; P= 0.01). CA-MRSA isolates were generally susceptible to clindamycin and trimethoprim-sulfamethoxazole and resistant to erythromycin. There were no significant differences in the exposure to risk factors between children with CA-MRSA and CA-MSSA infection. No significant risk factors for CA-MRSA were identified among household contacts. CONCLUSIONS: MRSA is an established, community-acquired pathogen in our area. This necessitates a change in empiric therapy of infections suspected to be caused by.