Safety and immunogenicity of a 2009 pandemic influenza A H1N1 vaccine when administered alone or simultaneously with the seasonal influenza vaccine for the 2009–10 influenza season: a multicentre, randomised controlled trial

• Published in: The Lancet (British edition) Vol. 375; no. 9708; pp. 49 - 55
• Main Authors: Vajo, Zoltan, Prof, Tamas, Ferenc, MD, Sinka, Laszlo, MD, Jankovics, Istvan, MD
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 02.01.2010; Elsevier; Elsevier Limited
• Subjects: Adjuvants; Adolescent; Adult; Aged; Aluminum; Antibodies; Autoimmune diseases; Avian flu; Biological and medical sciences; Blood products; Clinical medicine; Disease Outbreaks; Fatigue; Female; General aspects; Geriatrics; Hemagglutination Inhibition Tests; Hemagglutinins; Human viral diseases; Humans; Immune response; Immunization; Immunogenicity; Infectious diseases; Influenza A; Influenza A Virus, H1N1 Subtype - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza, Human - epidemiology; Influenza, Human - prevention & control; Internal Medicine; Male; Medical sciences; Middle Aged; Miscellaneous; Pain; Pandemics; Personnel; Phosphate; Primary care; Prospective Studies; Public health. Hygiene; Public health. Hygiene-occupational medicine; Seroconversion; Studies; Swine flu; Vaccination; Vaccines; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Virology; Womens health; Immune response; Toxicity; Multicenter study; Vaccine; Randomized controlled trial; Infection; 2009; Medicine; Prevention; Immunoprophylaxis; Immunogenicity; Seasonal variation; Viral disease; Clinical trial; Influenza A; Safety; Season; Public health
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(09)62039-0

Summary Background With the ongoing 2009 pandemic of influenza A H1N1, development of pandemic influenza vaccines has generated much interest. We investigated the safety and immunogenicity of a whole-virion, inactivated, adjuvanted pandemic H1N1 vaccine in adult and elderly volunteers, given without or simultaneously with the 2009–10 seasonal trivalent influenza vaccine. Methods This prospective, randomised study was undertaken in two centres in Hungary. 355 participants, including 203 adults (18–60 years) and 152 elderly people (>60 years), were assigned by stratified randomisation to either 0·5 mL of the pandemic vaccine (Fluval P, a monovalent vaccine with 6 μg haemagglutinin per 0·5 mL content and aluminium phosphate gel adjuvant; n=178) or 0·5 mL of the pandemic vaccine and 0·5 mL of the seasonal trivalent vaccine (Fluval AB, a trivalent inactivated whole-virion influenza vaccine; n=177). All vaccinations were done by specific study personnel, who did not take part in the assessment of safety or immunogenicity. Co-primary objectives were safety and immunogenicity by haemagglutinin inhibition testing. All analyses were done according to a pre-established analysis plan. This study is registered with ClinicalTrials.gov , number NCT01010893. Findings Two participants receiving the pandemic vaccine only (group 1) and one receiving pandemic and seasonal vaccines (group 2) were lost to follow-up. Participants in both groups developed antibody responses against the pandemic influenza A H1N1 virus (group 1: seroconversion for adults 74·3%, 95% CI 64–6–82·4 and for elderly people 61·3%, 49·1–72·4; group 2: 76·8%, 67·2–84·7 and 81·8%, 71·4–89·7, respectively). Single doses of 6 μg fulfilled European Union and US licensing criteria for interpandemic and pandemic influenza vaccines. Simultaneously, participants in group 2 developed the immune responses needed for licensing for all three seasonal strains in the seasonal vaccine for the 2009–10 season. All adverse events were rare, mild, and transient; the most frequent were pain at injection site (eight cases in group 1 vs 18 in group 2) and fatigue for 1–2 days after vaccination (three vs five cases). Interpretation The present pandemic vaccine is safe and immunogenic in healthy adult and elderly patients, and needs low doses and only one injection to trigger immune responses to comply with licensing criteria. It can be safely co-administered with the 2009–10 seasonal influenza vaccine. Funding Omninvest, Hungary.