Safety and immunogenicity of influenza whole inactivated virus vaccines: A phase I randomized clinical trial

• Published in: Human vaccines & immunotherapeutics Vol. 11; no. 4; pp. 983 - 990
• Main Authors: van Boxtel, Renée A J, Verdijk, Pauline, de Boer, Otto J, van Riet, Elly, Mensinga, Tjeert T, Luytjes, Willem
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.04.2015
• Subjects: Hemagglutination Inhibition Tests; Humans; immunogenicity; influenza; Influenza A Virus, H1N1 Subtype - immunology; Influenza, Human - prevention & control; pandemic; phase I trial; Research Paper; safety; seasonal; Vaccines, Inactivated - adverse effects; Vaccines, Inactivated - immunology; Vaccines, Inactivated - therapeutic use; whole inactivated virus vaccine; influenza; seasonal; safety; phase I trial; pandemic; whole inactivated virus vaccine; immunogenicity
• ISSN: 2164-5515; 2164-554X
• DOI: 10.1080/21645515.2015.1012004

BACKGROUND: Influenza vaccine production capacity is still insufficient to meet global demand in case of a pandemic. To expand worldwide influenza vaccine production capacity, a solid and transferable egg-based influenza vaccine production process was established that is suitable for upscaling and technology transfer to vaccine manufacturers in low- and middle-income countries. As a proof-of-concept, the safety and immunogenicity of a pandemic whole inactivated virus (WIV) vaccine (H5N1) and a monovalent seasonal WIV vaccine (H3N2) were evaluated in a phase I clinical trial in adults. METHODS: Subjects were vaccinated with 2 doses of pandemic WIV vaccine (pWIV), or one dose of either seasonal WIV vaccine (sWIV) or a commercially available trivalent comparator vaccine followed by a placebo dose. Haemagglutination inhibiting antibody titres against the influenza strains were determined before and 21 d after each vaccination. RESULTS: The frequency and severity of adverse reactions were comparable between groups. No serious adverse events were reported. After a single dose of sWIV the seroconversion rate was 91% (Committee for Proprietary Medicinal Products (CPMP) criterion >40%), the seroprotection rate was 100% (CPMP criterion >70%), and the mean geometric mean titre (GMT) increase was 24.9 (CPMP criterion >2.5). After two doses of pWIV, seroconversion rate and seroprotection rate were both 71%, and the mean GMT increase was 7.8. CONCLUSIONS: Both pWIV and sWIV were equally well-tolerated as the comparator vaccine, and both vaccines complied with all 3 CPMP criteria. EudraCT 2011-000159-17. Netherlands National Trial Register 2695.