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Title: A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice

item SHAO, HONGXIA - Yangzhou University
item YE, JIANQIANG - University Of Maryland
item Baker, Amy
item EDWORTHY, NICOLE - University Of Maryland
item FERRERO, ANDREA - University Of Maryland
item QIN, AIJIAN - Yangzhou University
item PEREZ, DANIELR - University Of Maryland

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/23/2011
Publication Date: 9/1/2011
Citation: Shao, H., Ye, J., Vincent, A.L., Edworthy, N., Ferrero, A., Qin, A., Perez, D. 2011. A novel monoclonal antibody effective against lethal challenge with swine-lineage and 2009 pandemic H1N1 influenza viruses in mice. Virology. 417(2):379-384.

Interpretive Summary: Influenza A virus causes a respiratory disease in swine similar to that in humans. In addition, it is a component of the multiple pathogen porcine respiratory disease complex in young pigs. Inactivated vaccines work well when pigs are exposed to influenza viruses represented in the vaccine. However, as with the situation in humans, influenza viruses continuously evolve and eventually vaccine efficacy is reduced when new strains no longer cross-react with the immunity induced by the vaccine. This requires continuous monitoring of new viruses and updating of strains used in vaccines. In this report, we developed a monoclonal antibody against the hemagglutinin of the 2009 A/H1N1 pandemic strain and found that it possessed high cross-reactivity and neutralizing activity against multiple H1N1 pandemic strains, but also against classical swine and other H1 strains that belong to clusters circulating among US swine. To our knowledge, this is the first report demonstrating a monoclonal antibody with broad cross-reaction against multiple swine H1 influenza lineages. Based on the high neutralization titer of this antibody and its ability to protect mice against lethal 2009 A/H1N1 pandemic and prototypic swine H1 virus challenge after intranasal administration either before or after virus challenge, this antibody has potential use as an immune therapy against swine-lineage H1 influenza viruses.

Technical Abstract: The HA protein of the 2009 pandemic H1N1viruses (14 H1N1pdm) is antigenically closely related to the HA of classical North American swine H1N1 influenza viruses (cH1N1). Since 1998, through reassortment and incorporation of HA genes from human H3N2 and H1N1 influenza viruses, swine influenza strains are undergoing substantial antigenic drift. In this report we describe the development of a novel monoclonal antibody (S-OIV-3B2) that shows high hemagglutination inhibition (HI) and neutralization titers against not only H1N1pdm, but also against representatives of the alpha, beta, and gamma clusters of swine-lineage H1 influenza viruses. Mice that received a single intranasal dose of S-OIV-3B2 (50 mg/kg) were protected against lethal challenge with either H1N1pdm or cH1N1 virus. These studies highlight the potential use of S23OIV-3B2 as effective intranasal prophylactic or therapeutic antiviral treatment for swine-lineage H1 influenza virus infections.