An adjuvanted, low-dose, pandemic influenza A (H5N1) vaccine candidate is safe, immunogenic, and induces cross-reactive immune responses in healthy adults.

BACKGROUND: To protect a naive global population against pandemic influenza, pandemic vaccines should be effective at low antigen doses, because of limited manufacturing capacity. METHODS: In a multicenter, randomized, blind-observer phase 1 trial, groups of 50 healthy young adults received 2 doses, 21 days apart, of influenza A/Vietnam/1194/2004 NIBRG-14 (H5N1) vaccine containing 1.9, 3.8, 7.5 or 15 microg of hemagglutinin with oil-in-water emulsion adjuvant or 7.5 microg of hemagglutinin without adjuvant. Safety was monitored to day 42. Homologous hemagglutination-inhibition (HI) and microneutralization titers were determined after each vaccination. Cross-reactivity against A/Indonesia/05/2005 RG2 was tested after the second vaccination. RESULTS: No vaccine-related significant or serious adverse events occurred. Injection site reactions, but not systemic reactions, were more frequent with adjuvant than without. Even with only 1.9 microg of hemagglutinin plus adjuvant, 72% of subjects had HI titers >or=1:32 after 2 doses. This proportion was 81%-89% with higher adjuvanted doses but was only 34% without adjuvant. Adjuvanted vaccine induced cross-neutralizing antibodies in 39%-65% of samples, versus 7% without adjuvant. CONCLUSIONS: The emulsion-adjuvanted pandemic influenza vaccine candidate was safe, immunogenic, and induced cross-reactive antibodies. This adjuvanted 1.9-microg candidate is the lowest effective dose tested to date. This could have a major impact on prepandemic vaccination strategies with stockpiled batches of vaccine. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00457509 .

Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11-15 years: a randomised controlled trial.

This trial assessed the immunogenicity, safety and reactogenicity of a two-dose hepatitis B immunisation regimen (thiomersal-free Engerix-B 20 microg HBsAg doses 6 months apart) compared to the standard three-dose vaccination regimen (preservative-free Engerix-B 10 microg HBsAg doses, 0, 1, 6 month dose schedule) in healthy adolescents aged 11-15 years. Subjects were randomly assigned (2:1 ratio) to one of the two regimens (258 to the two-dose [20 microg] and 126 to the three-dose [10 microg] regimen) (Study ID 103860/280). One month after the final vaccine dose, the seroprotection (anti-HBs >or=10mIU/ml) rate in the two-dose (20 microg) group (233/241 individuals -96.7% seroprotected) was non-inferior to the seroprotection rate in the three-dose (10 microg) group (111/113 individuals -98.2% seroprotected). Both regimens were shown to be safe and well tolerated. Two doses of Engerix-B (20 microg HBsAg) could be considered as an alternative to standard three-dose Engerix-B (10 microg HBsAg) immunisation for adolescents aged 11-15 years.

Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.

An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection.