ABSTRACT
OBJECTIVE: Our studies aimed to evaluate in clinical trials the safety and immunogenicity of an H5 live influenza vaccine candidate obtained using classical reassortment techniques from a low pathogenicity avian influenza (LPAI) A/Duck/Potsdam/1402-6/86(H5N2) virus and the cold-adapted (ca) donor strain A/Leningrad/134/17/57(H2N2). METHODS: During Phase I-II clinical trials, volunteers received intranasally two doses of reassortant influenza vaccine strain A/17/Duck/Potsdam/86/92 (H5N2) 21 days apart. Clinical examination of all vaccinees was conducted 7 days post-vaccination. Serum antibody responses were measured by hemagglutination-inhibition and microneutralization and local antibodies were estimated using an enzyme-linked immunosorbent assay test. RESULTS: The vaccine was safe and of low reactogenicity with no febrile reactions. After revaccination 47.1-54.8% of subjects showed > or =fourfold seroconversions of Hamagglutination inhibition (HAI) antibodies to the hemagglutinin (HA) antigen of the A/17/Duck/Potsdam/86/92 (H5N2) virus and 29.4-30.8% were seroconverted to the HA antigen of the reverse genetics reassortant A/Indonesia/05/2005 x PR8 IBCDC-RG (H5N1). Virus-neutralizing antibody levels in sera of volunteers were similar to those shown in HAI test. The virus-specific nasal IgA antibody response after two vaccine doses demonstrated significant increases of > or =fourfold rise SIgA antibodies (65%) geometrical mean titers (16.0) and a rise in SIgA antibodies (2.8) compared with one dose. CONCLUSION: The live attenuated influenza vaccine candidate prepared using the LPAI A(H5N2) strain was well tolerated and elicited serum and local immune responses. There was evident cross-reactivity to the A(H5N1) strain in the HAI test.
