Preclinical study of live cold-adapted reassortant influenza H1N1 pandemic and H7N3 vaccine candidates

The following paper describes the preclinical study of new H1N1 and H7N3 live attenuated influenza A vaccine (LAIV) candidates in mice. The study demonstrated that A/17/mallard/Netherlands/00/95 (H7N3) and A/17/California /2009/38 (H1N1) vaccine candidates were indistinguishable from parental A/Leningrad/134/17/57 (H2N2) master donor strain in terms of replication in the lungs and noses of mice at 3 and 6 days post-infection. It was found that both H7N3 and H1N1 LAIV and A/Leningrad/134/17/57 (H2N2) show no neuroivasive capacity and fail to replicate in the brains of mice. Immunization of mice with either 1000 MID(50) (50% mouse infectious dose) or 100 MID(50) of H7N3 LAIV protected mice from infection following a homologous challenge with wild-type H7N3 virus. Both H1N1 and H7N3 LAIV candidates were demonstrated to be immunogenic. After one dose of 100 MID(50) of H1N1 LAIV, the geometric mean titer (GMT) of hemagglutination inhibition (HI) antibodies was 17.6. One dose of 1000 MID(50) or 100 MID(50) H7N3 LAIV elicited an HI antibody with a GMT of 8 7 and 6 6, respectively. The second dose of H7N3 LAIV further increased of serum HI antibodies to a GMT 40 0 and 23 3 for 1000 MID(50) or 100MID(50), respectively. The study results confirm that new H1N1 LAIV and H7N3 LAIV candidates are safe and immunogenic and confer protection from homologues influenza virus infection in mice.