Safety and immunogenicity of influenza whole inactivated virus vaccines: A phase I randomized clinical trial.
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.
a Center for Infectious Diseases Control ; National Institute for Public Health and the Environment (RIVM) ; Bilthoven , The Netherlands.
Renée A J
RA
van Boxtel
Pauline
P
Verdijk
Otto J
OJ
de Boer
Elly
E
van Riet
Tjeert T
TT
Mensinga
Willem
W
Luytjes
D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D015164:Vaccines, Inactivated / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use
D015164:Vaccines, Inactivated
immunogenicity; influenza; pandemic; phase I trial; safety; seasonal; whole inactivated virus vaccine