Safety and immunogenicity of HCV E1E2 vaccine adjuvanted with MF59 administered to healthy adults.

BACKGROUND: Hepatitis C virus (HCV) causes chronic liver disease that often leads to cirrhosis and hepatocellular carcinoma. In animal studies, chimpanzees were protected against chronic infection following experimental challenge with either homologous or heterologous HCV genotype 1a strains which predominate in the USA and Canada. We describe the first in humans clinical trial of this prophylactic HCV vaccine. METHODS: HCV E1E2 adjuvanted with MF59C.1 (an oil-in-water emulsion) was given at 3 different dosages on day 0 and weeks 4, 24 and 48 in a phase 1, placebo-controlled, dose escalation trial to healthy HCV-negative adults. RESULTS: There was no significant difference in the proportion of subjects reporting adverse events across the groups. Following vaccination subjects developed antibodies detectable by ELISA, CD81 neutralization and VSV/HCV pseudotype neutralization. There were no significant differences between vaccine groups in the number of responders and geometric mean titers for each of the three assays. All subjects developed lymphocyte proliferation responses to E1E2 and an inverse response to increasing amounts of antigen was noted. CONCLUSIONS: The vaccine was safe and generally well-tolerated at each of the 3 dosage levels and induced antibody and lymphoproliferative responses. A larger study to further evaluate safety and immunogenicity is warranted.

Safety and immunogenicity of an intramuscular Helicobacter pylori vaccine in noninfected volunteers: a phase I study.

INTRODUCTION: Helicobacter pylori infection is among the most common human infections and the major risk factor for peptic disease and gastric cancer. Immunization with vaccines containing the H pylori vacuolating cytotoxin A (VacA), cytotoxin-associated antigen (CagA), and neutrophil-activating protein (NAP), alone or in combination, have been shown to prevent experimental infection in animals. AIM: We sought to study the safety and immunogenicity of a vaccine consisting of recombinant VacA, CagA, and NAP given intramuscularly with aluminium hydroxide as an adjuvant to noninfected healthy subjects. METHODS: This controlled, single-blind Phase I study randomized 57 H pylori-negative volunteers into 7 study arms exploring 2 dosages (10 and 25 microg) of each antigen and 3 schedules (0, 1, 2 weeks; 0, 1, 2 months; and 0, 1, 4 months) versus alum controls. All participants were followed for 5 months. Thirty-six subjects received a booster vaccination 18-24 months after the completion of the primary vaccination. RESULTS: Local and systemic adverse reactions were mild and similar in placebo and vaccine recipients on the monthly schedules. All subjects responded to 1 or 2 of the antigens and 86% of all vaccines mounted immunoglobulin G antibody responses to all 3 antigens. Vaccinees exhibited an antigen-specific cellular response. Vaccination 18-24 months later elicited anamnestic antibody and cellular responses. CONCLUSIONS: This intramuscular H pylori vaccine demonstrated satisfactory safety and immunogenicity, produced antigen-specific T-cell memory, and, therefore, warrants further clinical study.

Safety of MF59 adjuvant.

The need to enhance the immunogenicity of purified subunit antigens has prompted the development of new adjuvants. The adjuvant emulsion MF59 has been tested in animals in combination with different antigens and finally evaluated in humans. It was licensed after the successful outcome of preclinical and clinical testing. This paper summarizes the main characteristics of the MF59 adjuvant, including animal testing, clinical experience with various vaccines, and information from current postmarketing surveillance data. This review supports the hypothesis that MF59 is a safe adjuvant for human use.

Age-specific seroprevalence of serogroup C meningococcal serum bactericidal antibody activity and serogroup A, C, W135 and Y-specific IgG concentrations in the Turkish population during 2005.

Like many other developing countries; there is no accurate information about the antibody levels against Neisseria meningitidis in Turkey. We collected serum samples from four health centers located in different geographic regions and stratified according to age in order to obtain a baseline seroprevalence of protective antibodies to meningococcal serogroup C and provide data on seroprevalence of IgG antibodies to serogroups A, C, W135 and Y. Sera were tested for serum bactericidal antibodies (SBA) to serogroup C meningococci using rabbit serum as the complement source and by a bead based assay for serogroup A, C, W135 and Y-specific IgG. It was observed that 30% and 12% of individuals within the study population had SBA titers of > or =8 and > or =128, respectively. Overall; at least 70% of the population are susceptible (SBA titer <8) to meningococcal serogroup C disease. The rate of susceptibility was highest in infants aged 7-12 months and young children (1-4 years). Regardless of age, for serogroup A, C, W135 and Y, 60.5%, 27.2%, 12.3% and 19.2% of subjects, respectively, had serogroup-specific IgG concentrations > or =2 microg/mL. These data highlight that a large proportion of the Turkish population are susceptible to serogroups C, W135 and Y and should be considered, along with serogroup-specific disease incidence data, in future decisions on possible meningococcal vaccination programmes.