Abstract
Pigs are natural hosts for the same subtypes of influenza A viruses as humans and integrally involved in virus evolution with frequent interspecies transmissions in both directions. The emergence of the 2009 pandemic H1N1 virus illustrates the importance of pigs in evolution of zoonotic strains. Here we generated pig influenza-specific monoclonal antibodies (mAbs) from H1N1pdm09 infected pigs. The mAbs recognized the same two major immunodominant haemagglutinin (HA) epitopes targeted by humans, one of which is not recognized by post-infection ferret antisera that are commonly used to monitor virus evolution. Neutralizing activity of the pig mAbs was comparable to that of potent human anti-HA mAbs. Further, prophylactic administration of a selected porcine mAb to pigs abolished lung viral load and greatly reduced lung pathology but did not eliminate nasal shedding of virus after H1N1pdm09 challenge. Hence mAbs from pigs, which target HA can significantly reduce disease severity. These results, together with the comparable sizes of pigs and humans, indicate that the pig is a valuable model for understanding how best to apply mAbs as therapy in humans and for monitoring antigenic drift of influenza viruses in humans, thereby providing information highly relevant to making influenza vaccine recommendations.
Highlights
We show that prophylactic administration of one of these monoclonal antibodies (mAbs) to pigs abolished lung viral load and prevented lung damage following infection with influenza
Pigs are natural hosts for influenza A viruses (IAV) and closely related H1N1 and H3N2 viruses circulate in pigs and humans [1]
We developed porcine mAbs to pandemic H1N1 influenza virus which will increase the utility of the pig model in influenza virus research for evaluation of therapeutic mAbs and delivery platforms
Summary
Pigs are natural hosts for influenza A viruses (IAV) and closely related H1N1 and H3N2 viruses circulate in pigs and humans [1]. Frequent interspecies transmissions between pigs and humans contributes to the evolution of IAV and can be a source for novel pandemic strains [2,3,4]. Physiologically and immunologically more similar to humans than laboratory animals (mice, guinea pigs and ferrets) commonly used for influenza virus research [5,6]. Pigs and humans have similar distributions of sialic acid receptors in their respiratory tracts and longer life spans than laboratory animals which, with their more comparable size, makes them a useful stepping stone for translation of experimental results into human clinical applications. The dynamics of IAV transmission in pigs are well characterized and many immunologic tools, such as inbred strains, tetramers and antibodies for surface markers and cytokines are available to dissect porcine immune responses [7,8]. Pig mAbs against porcine epidemic diarrhoea, classical swine fever and porcine reproductive and respiratory syndrome viruses have been generated as candidates for passive immunotherapy and to aid vaccine design [9,10,11]
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