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Title:   Author  item
                                            LEWIS, NICOLA - University Of Cambridgeitem
                                            Anderson, Tavisitem
                                            Kitikoon, Pravinaitem
                                            SKEPNER, EUGENE - University Of Cambridgeitem
                                            BURKE, DAVID - University Of Cambridgeitem
                                            Baker, Amy
  Submitted to: Journal of Virology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 2/5/2014
                                    Publication  Date: 5/1/2014
                                    Citation: Lewis, N.S., Anderson, T.K., Kitikoon, P., Skepner, E., Burke, D.F., Vincent, A.L. 2014. Substitutions near the hemagglutinin receptor-binding site determine the antigenic evolution of influenza A H3N2 viruses in U.S. swine. Journal of Virology. 88(9):4752-4763.Interpretive Summary: Swine influenza A virus is an endemic and economically important pathogen in pigs with the potential to infect other host species including humans. Pigs may also become infected with human influenza A viruses. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of the changes in viral genetic material known as antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing how different strains in pigs are to the seasonal influenza strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. We found that two primary antigenic clusters circulate in the U.S. pig population, but with enough diversity between the HA proteins to suggest updates in vaccine strains are needed. We identified specific changes in the HA protein that are likely responsible for the antigenic differences. These changes may be useful in predicting when vaccines need to be updated. The antigenic difference between current seasonal influenza H3N2 strains in humans and those endemic in swine is enough that population immunity is unlikely to prevent the introduction of human viruses into pigs and vice-versa, reinforcing the need to monitor and prepare for potential incursions.
                                Technical Abstract: Swine influenza A virus is an endemic and economically important pathogen in pigs with the zoonotic potential to infect other host species. The hemagglutinin (HA) protein is the primary target of protective immune responses and the major component in swine influenza A vaccines. However, as a result of antigenic drift, vaccine strains must be regularly updated to reflect currently circulating strains. Characterizing the cross-reactivity between strains in pigs and seasonal influenza strains in humans is also important in assessing the relative risk of interspecies transmission of viruses from one host population to the other. Hemagglutination inhibition (HI) assay data for swine and human H3N2 viruses were used with antigenic cartography to quantify the antigenic differences among H3N2 viruses isolated from pigs in the USA from 1998-2012 and the relative cross-reactivity between these viruses and current human seasonal influenza A strains. Two primary antigenic clusters were found circulating in the pig population, but with enough diversity within and between the clusters to suggest updates in vaccine strains are needed. We identified single amino acid substitutions likely responsible for antigenic differences between the two primary antigenic clusters and between each antigenic cluster and outliers. The antigenic distance between current seasonal influenza H3 strains in humans and those endemic in swine is enough that population immunity is unlikely to prevent the introduction of human viruses into pigs and vice-versa, reinforcing the need to monitor and prepare for potential incursions.


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