ABSTRACT
This phase 1/2 open-label, randomized clinical study investigated the safety and immunogenicity of a non-adjuvanted, whole virus, Vero cell-derived H1N1 pandemic influenza vaccine (A/H1N1/California/07/2009) in children and adolescents (6 months to 17 years). Subjects were stratified by age (6-11 months, 12-35 months, 3-8 years, 9-17 years) to receive two vaccinations 21 days apart of either the 3.75 µg or 7.5 µg dose. A booster with a licensed trivalent seasonal (2010/2011) influenza vaccine was administered one year after the first vaccination to a subgroup that had previously received the 7.5 µg dose. A single vaccination with the 7.5 µg dose induced high seroprotection rates in all subjects, namely: 88.0% (9-17 years); 68.0% (3-8 years); 42.9% (12-35 months); and 50.0% (6-11 months). Following a second vaccination, seroprotection rates ranged from 84.2% to 100%. GMTs after two vaccinations with the 7.5 µg dose (as determined by HI) were also substantial: reaching 210.0 (9-17 years), 196.2 (3-8 years), 118.9 (12-35 months) and 99.6 (6-11 months). Antibody persistence was demonstrated at 6 months (GMTs ranging from 65.6 to 212.8 with the 7.5 µg dose) and at 12 months (GMTs ranging from 33.6 to 124.1 with the 7.5 µg dose) after primary vaccination. The booster vaccination induced a strong response to the A/California/07/2009 strain, reaching 100% seroprotection in all age groups, with GMTs ranging from 640.0 to 886.3. The vaccine was well tolerated, inducing low adverse reaction rates (overall fever rate: 6% after the first vaccination; 7% after the second vaccination), even in young children. These data confirm that the H1N1 whole-virus Vero cell-derived pandemic influenza vaccine is suitable for use in children and adolescents; a 2-dose primary vaccination induces a memory response in a naïve population that can be effectively boosted with the A/H1N1/California/07/2009 component of a seasonal influenza vaccine. ClinicalTrials.gov Identifier: NCT00976469.
Subject(s)
Immunologic Memory , Influenza A Virus, H1N1 Subtype/pathogenicity , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Adolescent , Animals , Antibodies, Viral/blood , Child , Child, Preschool , Chlorocebus aethiops , Dose-Response Relationship, Immunologic , Humans , Immunization Schedule , Immunization, Secondary , Infant , Influenza Vaccines/immunology , Influenza, Human/immunology , Injections, Intramuscular , Vaccination/methods , Vero CellsABSTRACT
Tick-borne encephalitis (TBE) vaccination strategies to induce optimal seroprotection in children are under constant evaluation. This multi-center, randomized, controlled, phase III clinical study examined antibody persistence in children aged 1-11 y following two prospectively administered doses of either the FSME-IMMUN® Junior or Encepur Children® vaccines, as well as investigating the immunogenicity, safety and vaccine interchangeability of a third vaccination with FSME-IMMUN(®) Junior. A high level of antibody persistence was observed in all subjects 6 mo after the first of two vaccinations with either pediatric TBE vaccine. Based on both immunological tests and viral antigens used, slightly higher seropositivity rates and higher GMCs /GMTs were found in children vaccinated with FSME-IMMUN® Junior compared with those who received Encepur® Children. Seropositivity rates across all age strata combined six months after the first vaccination with FSME-IMMUN® 0.25 mL Junior were 95.1% as determined by Immunozym ELISA, 93.2% as determined by Enzygnost ELISA and 95.3% as determined by NT; compared with 62.6%, 80.5% and 91.0% respectively after vaccination with Encepur® Children. A third vaccination with FSME-IMMUN(®) Junior induced 100% seropositivity in both study groups and was well tolerated as demonstrated by the low rates of systemic and injection site reactions. Subjects who received either FSME-IMMUN Junior® or Encepur(®) Children vaccine for the first two vaccinations and FSME-IMMUN Junior® for the third showed a comparably strong immune response regardless of the previous TBE vaccine administered, demonstrating that two vaccinations with Encepur® Children can successfully be followed by a third vaccination with FSME-IMMUN Junior®.
Subject(s)
Encephalitis, Tick-Borne/immunology , Encephalitis, Tick-Borne/prevention & control , Vaccination/methods , Viral Vaccines/therapeutic use , Child , Child, Preschool , Encephalitis Viruses, Tick-Borne/immunology , Encephalitis Viruses, Tick-Borne/pathogenicity , Female , Humans , Infant , Male , Prospective StudiesABSTRACT
TBE vaccination strategies capable of inducing strong paediatric immunogenicity and acceptable reactogenicity are still under evaluation. This single-blind, multi-center, randomized, controlled, phase III clinical study compared the immunogenicity and safety of the two paediatric TBE vaccines available in Europe (FSME-IMMUN Junior and Encepur Children) following administration of two doses of either vaccine in 303 children aged 1-11 years. Regardless of immunological test or viral antigen used, immunological responses were consistently higher in children vaccinated with FSME-IMMUN Junior than those vaccinated with Encepur Children. FSME-IMMUN Junior is also non-inferior to Encepur Children, with respect to NT seropositivity rates (p<0.0001). Systemic reaction rates were low and similar between the vaccines. However, among children aged 7-11 years, local reactions were significantly higher after the first (p<0.01) and second (p<0.001) vaccination with Encepur Children than with FSME-IMMUN Junior, affecting half the children in the former group: 22.4% and 10.2% with FSME-IMMUN Junior vs. 49.0% and 51.0% for Encepur Children.
