Submitted to: Journal of Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 8/19/2010
Publication Date: 11/1/2010
Citation: Min, J., Vogel, L., Matsuoka, Y., Lu, B., Swayne, D.E., Jin, H., Kemble, G., Subbarao, K. 2010. A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets and monkeys. Journal of Virology. 84(22):11950-11960. Interpretive Summary: Various avian influenza viruses have an unknown potential to become human pandemic influenza viruses. This study developed an H7N7 live weakened virus vaccine for humans by using advanced biotechnology to make the virus able to grow only at lower than normal body temperature of the nasal cavity. This vaccine had reduced replication in chickens, did not cause disease in mice which are animal models for humans, and only grew at the lower temperatures in the nasal cavity. Administering the vaccine in the nose protected mice, ferrets and monkeys against challenge by H7 influenza virus which supports further evaluation of the vaccine in clinical trials.
Technical Abstract: A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of HP A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (H2N2) virus. The reassortant H7N7 NL/03 ca vaccine virus was temperature sensitive and attenuated in mice, ferrets, and African green monkeys (AGMs). Intranasal (i.n.) administration of a single dose of the H7N7 NL/03 ca vaccine virus fully protected mice from lethal challenge with homologous and heterologous H7 viruses from Eurasian and North American lineages. Two doses of the H7N7 NL/03 ca vaccine induced neutralizing antibodies in the serum and provided complete protection from pulmonary replication of homologous and heterologous wild-type H7 challenge viruses in mice and ferrets. One dose of the H7N7 NL/03 ca vaccine elicited an antibody response in one of three AGMs that was completely protected from pulmonary replication of the homologous wild-type H7 challenge virus. The contribution of CD8+ and/or CD4+ T cells to the vaccine-induced protection in mice was evaluated by T cell depletion; T lymphocytes were not essential for the vaccine-induced protection from lethal challenge with H7 wt viruses. Additionally, passively transferred neutralizing antibody induced by H7N7 NL/03 ca virus protected mice from lethality following challenge with H7 wt viruses. The safety, immunogenicity, and efficacy of H7N7 NL/03 ca vaccine virus in mice, ferrets and AGMs support the evaluation of this vaccine virus in Phase 1 clinical trials.