LID scientists are collaborating with scientists from MedImmune under a CRADA to generate candidate vaccines against avian influenza viruses of each subtype. The vaccines were generated using plasmid based reverse genetics and each contains the hemagglutinin and neuraminidase genes from an avian influenza virus and six internal gene segments from the AA ca virus. Since 1968, human H3N2 influenza viruses have been circulating worldwide, and the population has been infected by and/or vaccinated against these viruses. However, H3 subtype influenza viruses have been isolated from humans, pigs, horses, dogs, cats, seals, and numerous avian species, and these viruses are antigenically and genetically distinct from human H3 viruses. Swine, equine, and avian H3 influenza viruses all have crossed the species barrier to mammals, including humans, dogs, and seals. Very little information is available on the kinetics of replication and cross-reactivity of the immune response of swine, equine, and avian H3 influenza viruses in experimental animal models. Based on the emergence of a swine-origin H1N1 virus as a pandemic strain in 2009 despite the ongoing circulation of human H1viruses, we believe it is necessary to consider the development of H3 animal influenza vaccines. We selected 11 swine, equine, and avian H3 influenza viruses and evaluated their kinetics of replication and ability to induce a broadly cross-reactive antibody response in mice and ferrets. The swine and equine viruses replicated well in the upper respiratory tract of mice. With one exception of an avian virus that replicated poorly in the lower respiratory tract, all of the viruses replicated in mouse lungs. In ferrets, all of the viruses replicated well in the upper respiratory tract, but the equine viruses replicated poorly in the lungs. Extrapulmonary spread was not observed in either mice or ferrets. No single virus elicited antibodies that cross-reacted with viruses from all three animal sources. Avian and equine H3 viruses elicited broadly cross-reactive antibodies against heterologous viruses isolated from the same or other species, but the swine viruses did not. We selected an equine and an avian H3 influenza virus for further development as vaccines.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Boonnak, Kobporn; Vogel, Leatrice; Feldmann, Friederike et al. (2014) Lymphopenia associated with highly virulent H5N1 virus infection due to plasmacytoid dendritic cell-mediated apoptosis of T cells. J Immunol 192:5906-12
Chen, Zhongying; Baz, Mariana; Lu, Janine et al. (2014) Development of a high-yield live attenuated H7N9 influenza virus vaccine that provides protection against homologous and heterologous H7 wild-type viruses in ferrets. J Virol 88:7016-23
Matsuoka, Yumiko; Suguitan Jr, Amorsolo; Orandle, Marlene et al. (2014) African green monkeys recapitulate the clinical experience with replication of live attenuated pandemic influenza virus vaccine candidates. J Virol 88:8139-52
Chen, Grace L; Lamirande, Elaine W; Cheng, Xing et al. (2014) Evaluation of three live attenuated H2 pandemic influenza vaccine candidates in mice and ferrets. J Virol 88:2867-76
Baz, Mariana; Paskel, Myeisha; Matsuoka, Yumiko et al. (2013) Replication and immunogenicity of swine, equine, and avian h3 subtype influenza viruses in mice and ferrets. J Virol 87:6901-10
Chen, Zhongying; Santos, Celia; Aspelund, Amy et al. (2009) Evaluation of live attenuated influenza a virus h6 vaccines in mice and ferrets. J Virol 83:65-72
Scull, Margaret A; Gillim-Ross, Laura; Santos, Celia et al. (2009) Avian Influenza virus glycoproteins restrict virus replication and spread through human airway epithelium at temperatures of the proximal airways. PLoS Pathog 5:e1000424
Fornek, Jamie L; Gillim-Ross, Laura; Santos, Celia et al. (2009) A single-amino-acid substitution in a polymerase protein of an H5N1 influenza virus is associated with systemic infection and impaired T-cell activation in mice. J Virol 83:11102-15
Matsuoka, Yumiko; Lamirande, Elaine W; Subbarao, Kanta (2009) The ferret model for influenza. Curr Protoc Microbiol Chapter 15:Unit 15G.2
Matsuoka, Yumiko; Swayne, David E; Thomas, Colleen et al. (2009) Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J Virol 83:4704-8

Showing the most recent 10 out of 13 publications