LIVE ATTENUATED INFLUENZA A H5N1 CANDIDATE VACCINES ARE IMMUNOGENIC AND HIGHLY EFFICACIOUS AGAINST HOMOLOGOUS AND HETEROLOGOUS H5N1 VIRUS CHALLENGE IN MICE

Authors: SUGUITAN, JR, A - NIAID-NIH - BETHESDA, MD; MCAULIFFE, J - NIAID-NIH - BETHESDA, MD; MILLS, K - NIAID-NIH - BETHESDA, MD; LU, B - MEDIMMUNE VAC, INC, CA; JIN, H - MEDIMMUNE VAC, INC, CA; LUKE, C - NIAID-NIH - BETHESDA, MD; MURPHY, B - NIAID-NIH - BETHESDA, MD; Swayne, David; KEMBLE, G - MEDIMMUNE VAC, INC, CA; SUBBARAO, K - NIAID-NIH - BETHESDA, MD

Submitted to: International Conference on Negative Strand Viruses
Publication Type: Abstract Only
Publication Acceptance Date: 5/1/2006
Publication Date: 6/17/2006
Citation: Suguitan, Jr, A.L., Mcauliffe, J., Mills, K.L., Lu, B., Jin, H., Luke, C.J., Murphy, B., Swayne, D.E., Kemble, G., Subbarao, K. 2006. Live attenuated influenza A H5N1 candidate vaccines are immunogenic and highly efficacious against homologous and heterologous H5N1 virus challenge in mice [abstract]. Abstracts of the 13th International Conference on Negative Strand Viruses. p. 197.

Interpretive Summary:

Technical Abstract: Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species underscore an urgent need to develop vaccines that would protect humans in the event of a pandemic. Live attenuated candidate vaccines possessing a modified H5 hemagglutinin (HA) and N1 neuraminidase genes from influenza A H5N1 viruses isolated in Hong Kong in 1997 and 2003 and in Vietnam in 2004 and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses displayed phenotypes predicted by the modification engineered in the HA gene and those specified by the internal protein genes of the ca vaccine donor strain. The candidate vaccines were immunogenic in mice. Serum neutralizing and hemagglutination-inhibiting antibodies were detected 8 weeks after one dose of vaccine; two doses of vaccine resulted in higher titer and cross-reactive serum antibodies. Four weeks after administration of a single dose of intranasally administered vaccine, mice were fully protected from lethal challenge with homologous and antigenically distinct heterologous wild-type (wt) H5N1 viruses from clades 1 and 2 isolated in Asia between 1997 and 2005. Four weeks after two doses of the vaccines, complete protection was observed against pulmonary replication of homologous and heterologous wt H5N1 viruses. The promising findings of immunogenicity and efficacy against antigenically diverse H5N1 viruses in these preclinical studies provide support for careful evaluation of the live attenuated H5N1 ca vaccines in a Phase 1 clinical trial in humans.