Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus.

Objective: Patients with diabetes mellitus are at increased risk for hepatitis B virus (HBV) infection and its complications. HBV vaccination is recommended for adults with diabetes in the United States and other countries. However, few studies have assessed safety and immunogenicity of hepatitis B vaccine in such patients. We assessed the safety and immunogenicity of recombinant hepatitis B vaccine in subjects with and without diabetes mellitus. METHODS: Prospective, multi-country controlled study in 21 centers ( www.clinicaltrials.gov NCT01627340). Four hundred and sixteen participants with Type-2 diabetes and 258 controls matched for age and body mass index (BMI) (2:1 ratio) received 3-doses of HBV vaccine (Engerix-B™, GSK Vaccines, Belgium) according to a 0, 1, 6 months schedule. Antibodies were measured against HBV surface antigen and expressed as seroprotection rates (anti-HBs ≥10mIU/mL) and geometric mean concentration (GMC). RESULTS: The median age and BMI in patients with diabetes and controls (according-to-protocol cohort) were 54 y and 32.1 kg/m2, and 53 y and 30.8 kg/m2, respectively. Seroprotection rates (GMCs) one month post-dose-3 were 75.4% (147.6 mIU/mL) and 82.0% (384.2 mIU/mL) in patients with diabetes and controls, respectively. Age-stratified seroprotection rates for patients with diabetes were 88.5% (20-39 years), 81.2% (40-49 years), 83.2% (50-59 years), and 58.2% (≥60 years). The overall safety profile of hepatitis B vaccine was similar between groups. CONCLUSIONS: Hepatitis B vaccine is immunogenic in patients with diabetes and has a similar safety profile to vaccination in healthy controls. Because increasing age was generally associated with a reduction in seroprotection rates, hepatitis B vaccine should be administered as soon as possible after the diagnosis of diabetes.

Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with measles-mumps-rubella and varicella vaccines in children less than 2 years of age.

BACKGROUND: Hepatitis A vaccination in early childhood has reduced hepatitis A transmission. Coadministration of hepatitis A vaccine with other childhood vaccines may assist completion of the age-appropriate immunization schedule. We assessed the immunogenicity and safety of an inactivated hepatitis A virus vaccine when coadministered with measles-mumps-rubella (MMR) and varicella vaccines in children less than 2 years of age. METHODS: In this open-label, randomized, multicenter study, 3 groups of healthy children 15 months of age received either 2 doses of hepatitis A vaccine 6 to 9 months apart (n = 324), hepatitis A vaccine coadministered with MMR and varicella vaccines and a second dose of hepatitis A vaccine 6 to 9 months later (n = 462), or MMR and varicella vaccines followed 6 weeks later by 2 doses of hepatitis A vaccine 6 to 9 months apart (n = 455). Immune responses were evaluated at baseline, 31 days after the second dose of hepatitis A vaccine, and 42 days after MMR and varicella vaccine administration. Solicited, unsolicited, and serious adverse events were collected. RESULTS: After 2 doses of hepatitis A vaccine, nearly all subjects in all groups were seropositive (≥99%). Coadministration of hepatitis A vaccine with MMR and varicella vaccines did not impact the immunogenicity of any of the vaccines and was well tolerated. CONCLUSIONS: The immune response to hepatitis A vaccine and US-licensed MMR and varicella vaccines is not adversely affected when coadministered in children 15 months of age.

Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age.

BACKGROUND: This study (NCT00197236) evaluated the safety and immunogenicity of a hepatitis A virus (HAV) vaccine when coadministered with diphtheria-tetanus-acellular pertussis (DTaP) and Haemophilus influenzae type b (Hib) vaccines in children 15 months of age. METHODS: This was an open-labeled, multicenter study with healthy subjects enrolled and randomized (1:1:1) into 3 treatment groups. A total of 394 subjects received the first study vaccinations at 15 months of age. Group HAV (N = 135) received 2 doses of HAV vaccine 6 to 9 months apart. Group HAV+DTaP+Hib (N = 127) received HAV vaccine coadministered with DTaP and Hib vaccines and the second dose of HAV vaccine, 6 to 9 months later. Group DTaP+Hib→HAV (N = 132) received the DTaP and Hib vaccines at 15 months of age, followed by HAV vaccine 30 days later and the second dose of HAV vaccine 7 to 10 months after the DTaP+Hib vaccines. Immune responses were evaluated before the first study vaccination and 30 days after each vaccine dose. Solicited, unsolicited, and serious adverse events were collected. RESULTS: After 2 doses of the HAV vaccine, all subjects in the 3 groups were seropositive. The geometric mean concentration of anti-HAV antibodies ranged between 1625.1 and 1904.4 mIU/mL. Coadministration of the 3 vaccines did not impact immunogenicity of the HAV, DTaP, or Hib vaccines. Vaccines were well tolerated in all groups. CONCLUSIONS: A 2-dose schedule of HAV vaccine was well tolerated and immunogenic when administered to children starting at 15 months of age. Immune responses to the DTaP or Hib vaccines were similar whether they were administered alone or were coadministered with the HAV vaccine.

Comparison of the immunogenicity and safety of Cervarix and Gardasil human papillomavirus (HPV) cervical cancer vaccines in healthy women aged 18-45 years.

This observer-blind study compared the prophylactic human papillomavirus (HPV) vaccines, Cervarix (GlaxoSmithKline) and Gardasil (Merck), by assessing immunogenicity and safety through one month after completion of the three-dose vaccination course. Women (n = 1106) were stratified by age (18-26, 27-35, 36-45 years) and randomized (1:1) to receive Cervarix (Months 0, 1, 6) or Gardasil (Months 0, 2, 6). At Month 7 after first vaccination, all women in the according-to-protocol cohort who were seronegative/DNA negative before vaccination for the HPV type analyzed had seroconverted for HPV-16 and HPV-18 serum neutralizing antibodies, as measured by pseudovirion-based neutralization assay (PBNA), except for two women aged 27-35 years in the Gardasil group who did not seroconvert for HPV-18 (98%). Geometric mean titers of serum neutralizing antibodies ranged from 2.3-4.8-fold higher for HPV-16 and 6.8-9.1-fold higher for HPV-18 after vaccination with Cervarix compared with Gardasil, across all age strata. In the total vaccinated cohort (all women who received at least one vaccine dose, regardless of their serological and DNA status prior to vaccination), Cervarix induced significantly higher serum neutralizing antibody titers in all age strata (p < 0.0001). Positivity rates for anti-HPV-16 and -18 neutralizing antibodies in cervicovaginal secretions and circulating HPV-16 and -18 specific memory B-cell frequencies were also higher after vaccination with Cervarix compared with Gardasil. Both vaccines were generally well tolerated. The incidence of unsolicited adverse events was comparable between vaccinated groups. The incidence of solicited symptoms was generally higher after Cervarix, injection site reactions being most common. However, compliance rates with the three-dose schedules were similarly high (>or= 84%) for both vaccines. Although the importance of differences in magnitude of immune response between these vaccines is unknown, they may represent determinants of duration of protection against HPV-16/18. Long-term studies evaluating duration of efficacy after vaccination are needed for both vaccines.

Immunogenicity and safety of an inactivated hepatitis a vaccine administered concomitantly with a pneumococcal conjugate vaccine in healthy children 15 months of age.

The immunogenicity and safety of hepatitis A vaccine and pneumococcal conjugate vaccine, administered separately or concomitantly in children 15 months of age, were evaluated. After completed vaccinations, antihepatitis A and antipneumococcal geometric mean concentrations were similar across groups. Both vaccines were well-tolerated when given concomitantly during the second year of life.

Rapid and sustained immune response against hepatitis A and B achieved with combined vaccine using an accelerated administration schedule.

BACKGROUND: Combined hepatitis A and B vaccine administered on an accelerated schedule provides a rapid immune response against both hepatitis A and B viruses, which might be especially relevant for individuals who need protection quickly. METHODS: A prospective, open-label, randomized study to compare the immunogenicity and reactogenicity of the combined hepatitis A and B vaccine Twinrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) (>or=720 EL.U/mL inactivated hepatitis A antigen and 20 microg/mL recombinant hepatitis B surface antigen [HBsAg]) administered at 0, 7, 21 to 30 days, and 12 months compared with concurrent administration of Havrix [GlaxoSmithKline Biologicals, Rixensart, Belgium (>or=1440 EL.U/mL inactivated hepatitis A antigen)] at 0 and 12 months, and Engerix-B [GlaxoSmithKline Biologicals, Rixensart, Belgium (20 microg/mL recombinant HBsAg)] at 0, 1, 2, and 12 months in seronegative healthy adults. RESULTS: At month 13, the anti-hepatitis B seroprotection rates (>10 mIU/mL) for the combined vaccine compared to the monovalent hepatitis B vaccine were 96.4% (95% CI: 92.7-98.5) and 93.4% (95% CI: 89.0-96.4), respectively. The anti-hepatitis A seroconversion rates were 100% in both groups (95% CI: 98.1-100). At day 37, the anti-hepatitis A seroconversion rates were similar in both groups (98.5% for combined vaccine, 98.6% for the monovalent vaccine group), but the combined vaccine resulted in a statistically significantly ( p < 0.001) better anti-hepatitis B seroprotection compared to monovalent hepatitis B vaccine, 63.2% versus 43.5%, respectively. The reactogenicity profile was similar in both study groups. CONCLUSIONS: The combined hepatitis A and B vaccine administered on an accelerated schedule was at least as immunogenic and as well tolerated as the corresponding monovalent vaccines.