Immunogenicity and Safety of H5N1 A/Vietnam/1194/2004 (Clade 1) AS03-adjuvanted prepandemic candidate influenza vaccines in children aged 3 to 9 years: a phase ii, randomized, open, controlled study.

BACKGROUND: The development of vaccines against pandemic influenza viruses for use in children is a public health priority. METHODS: In this phase II, randomized, open study, the immunogenicity and reactogenicity of H5N1 A/Vietnam/1194/2004 (NIBRG-14) (clade 1) prepandemic influenza vaccine were assessed in children aged 3 to 5 and 6 to 9 years. Children were randomized to receive 2 doses, given 21 days apart, of A/Vietnam/1194/2004 vaccine containing 1.9 microg or 3.75 microg hemagglutinin antigen (HA), adjuvanted with a tocopherol-based oil-in-water emulsion (AS03) containing 11.86 mg (AS03(A)) or 5.93 mg (AS03(B)) tocopherol. Control groups received 2 doses of trivalent influenza vaccine (TIV). Humoral immune responses, reactogenicity, and safety were the primary outcome measures; cross-reactivity and cell-mediated responses were also assessed (NCT00502593). RESULTS: Between 49 and 51 children in each age stratum (aged 3-5 and 6-9 years) received H5N1 vaccine, and between 17 and 18 children in each age stratum received TIV. After the second dose, recipients of H5N1 vaccine (1.9 microg HA/AS03(B), 3.75 microg HA/AS03(B), and 3.75 microg HA/AS03(A)) achieved humoral antibody titers against the vaccine-homologous strain, which fulfilled the United States influenza vaccines licensure criteria for immunogenicity. With the exception of 1 child, there were no H5N1 immune responses in children who received TIV. The most frequent injection-site event was pain in all groups, and the H5N1 vaccine had a clinically acceptable reactogenicity and safety profile. Exploratory analyses in children aged 3 to 5 years indicated that the induction of CD4 T-cell responses polarized in favor of a T-helper 1 profile. CONCLUSIONS: The results showed that 2 doses of AS03-adjuvanted H5N1 influenza vaccine at antigen-sparing doses of 1.9 microg or 3.75 microg HA elicited broad and persistent immune responses with acceptable reactogenicity, and without safety concerns, in children aged 3 to 9 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.

Incidence of pertussis in persons < or =15 years of age in Valencia, Spain: seroprevalence of antibodies to pertussis toxin (PT) in children, adolescents and adults.

PURPOSE: To determine the incidence of pertussis in persons < or =15 years in age in Valencia, Spain. To assess the prevalence of IgG antibodies to pertussis toxin (PT) in children, adolescents and adults. METHODS: Prospective study conducted at paediatric primary care centres. All persons < or =15 years in age presented with persistent cough were enrolled. Parents completed a brief questionnaire and immunization history was obtained from paediatrician records. A blood sample was obtained, for determination of IgG antibodies to Bordetella pertussis toxin (PT) by an ELISA method. A study confirmed-case was the presence of two conditions: (1) cough illness of > or =14 days duration; and (2) ELISA absorbance value of IgG to PT > or =2. Two subjects per clinical-case (same centre and range of age) and parents were asked to participate in the prevalence study. RESULTS: Sixty-one children < or =15 years in age presented with symptoms leading to a clinical diagnosis of pertussis were detected. Serological evidence of recent pertussis was found in five of these patients (incidence of 46.0/100,000 persons < or =15 years in age). Prevalence of antibodies to B. pertussis (> or =0.3) in children < or =15 years in age and adults was 39 and 33%, respectively. Only a minority of children, adolescents and adults had absorbance values indicative of immunity (> or =1). CONCLUSIONS: These incidence and seroprevalence results show that despite high immunization rates in infancy, B. pertussis is circulating in Spain.