Poster Presentation Lorne Infection and Immunity 2013

THE INFLUENCE OF PROTECTIVE HETEROLOGOUS ANTIBODIES ON THE HOST IMMUNE RESPONSE IN A MOUSE MODEL OF INFLUENZA VIRUS INFECTION (#151)

Catherine Rinaldi 1 , William J Penhale 2 , Guan Tay 1 , Cassandra M Berry 2
  1. Centre for Forensic Science, University of Western Australia, Perth, WA, Australia
  2. School of Veterinary and Biomedical Science, Murdoch University, Perth, WA, Australia

Emerging influenza viruses pose a serious global threat despite current vaccine technology, which has limited effectiveness during a pandemic due to delayed production. A potential adjunct approach capable of alleviating this inefficiency, whilst a strain-specific vaccine is produced, is passive immunisation using neutralising anti-influenza virus antibodies. A potential large scale production source of antibodies is large ruminants and when such ruminant polyclonal antibodies are delivered intranasally, we and others have demonstrated protection against influenza virus infection. However, knowledge of the influence of these protective heterologous antibodies on development of the host immune response to the virus is limited. Importantly, type I and type III Interferons (IFN) are produced early in the innate immune response to influenza virus, exerting both anti-viral and immunomodulatory properties controlling the infection and subsequent adaptive immune response. We generated influenza virus-specific IgG antibodies by vaccinating sheep with a purified split influenza virus vaccine and demonstrated that these antibodies have high virus neutralisation titres and upon intranasal delivery to BALB/c mice prior to infection can fully protect mice from pulmonary influenza A/PR/8/34 virus infection. Protected mice had no detectable influenza virus replication in the lungs at three days post-intranasal infection. Similarly, full protection was provided by influenza virus specific F(ab’)2 antibody fragments suggesting that protection was primarily provided by immune exclusion of the virus. Type I and III IFN cytokine levels in the bronchial lavage fluid, measured by IFN-α/β bioassay and anti-IFN-λ ELISA, were not induced in protected antibody-treated mice. Low titres of influenza virus-specific antibody were detected by ELISA in the serum of protected mice, in contrast to an anti-sheep antibody response. This research represents the first investigation of the influence of ruminant antibody prophylaxis on modifying the host immune response to influenza virus infection, which has potential for improved strategies to combat influenza.