Overview of swine influenza virus vaccine research and technology: What's on the horizon and what do we need to move forward?

Authors: Kehrli Jr, Marcus; Baker, Amy; GAUGER, PHILLIP - Iowa State University; Kitikoon, Pravina; Anderson, Tavis; Loving, Crystal; Lager, Kelly

Submitted to: American Association of Swine Veterinarians Annual Meeting
Publication Type: Proceedings
Publication Acceptance Date: 11/29/2012
Publication Date: 3/13/2013
Citation: Kehrli, Jr., M.E., Vincent, A.L., Gauger, P.C., Kitikoon, P., Anderson, T.K., Loving, C.L., Lager, K.M. 2013. Overview of swine influenza virus vaccine research and technology: What's on the horizon and what do we need to move forward? In: Proceedings of 44th Annual Meeting of the American Association of Swine Veterinarians, San Diego, CA. p. 517-519.

Interpretive Summary:

Technical Abstract: Introduction Swine influenza represents a problem for the health of pigs and the economic health of the swine industry due to real and perceived public health risks. This is largely driven by the diversity of influenza A viruses (IAV) in swine herds. Antigenic drift (mutations) and shifts (reassortments) by influenza viruses are continually occurring. The RNA polymerase error rate among IAV is ~2 X 10**-3 nucleotide substitutions/site/year(1) and whenever a single cell is infected by 2 different influenza viruses, reassortment events between the viruses can occur and result in as many as 256 different gene combinations. These 2 types of genetic change provide the basis of the marked genetic and antigenic diversity in contemporary IAV in North American swine. In addition, interspecies transmission is an important contributor to the genetic diversity of IAV found in swine. For example, at least 23 separate human-to-swine transmission events of human seasonal H1 and H3 influenza viruses have been identified globally since 1990.(2) The global ecology of influenza A viruses (IAV) in swine can be separated by geographic regions, with North American lineages genetically distinct from European swine lineages. In North America, the classical swine H1N1 virus was dominant until the seasonal human H3N2 virus was introduced into pigs in 1998(3) and followed by at least two additional, separate introductions of human H1 viruses.(4) At present, seven major antigenically distinct hemagglutinin (HA) lineages, H1alpha, H1beta, H1gamma, H1delta1, H1delta2, H1N1pdm09 and H3 cluster IV (c4) co-circulate in North American swine populations.(5) Until 2009, all dominant HA lineages except for the H1N1pdm09 virus contained the 'triple reassorted internal gene' (TRIG) constellation of swine (M, NP and NS genes), avian (PB2 and PA genes), and human (PB1) lineages identified in swine in 1998. The internal gene constellation in H1N1pdm09 is distinct from the H3N2-TRIG as the M gene is of Eurasian swine lineage and the other 5 genes can be differentiated in a phylogenetic analysis.(6) Within two years after the emergence of H1N1pdm09 in humans, at least 49 influenza spillover events from humans-to-swine were detected globally.(2) The introduction of H1N1pdm09 into pigs subsequently led to multiple reassortment events between H1N1pdm09 and the endemically circulating IAV of swine, greatly increasing the genetic diversity of IAV in swine.(7) Public health concerns impact swine influenza vaccination needs Nothing has highlighted the economic impact of IAV on swine production more than the emergence of the H1N1pdm09. The H3N2-TRIG/H1N1pdm09 (rH3N2p) reassortant viruses are of particular public health concern in the United States; between August 2011 and November 2012, there have been 319 human infections (http://www.cdc.gov/flu/swineflu/h3n2v-case-count.htm) by a variant comprised of 7 genes from swine H3N2 and the M gene of H1N1pdm09 (H3N2v).(8,9) The number of H3N2v human cases highlights the need for IAV whole genome characterization to further understand the evolution of reassortant H3N2/H1N1pdm09 (rH3N2p) viruses in swine and humans, and may indicate a need for vaccine or diagnostic assay updates for both populations. In veterinary medicine, we have a higher bar to clear than to simply protect against clinical disease in pigs. Indeed, the human-to-swine and swine-to-human transmission pathways suggest that a vaccine priority should be protection and prevention against transmission of viruses from pigs to other pigs and from pigs to people. This is a much more difficult goal than what is required for human vaccines and current inactivated vaccines are not adequately addressing the public nor swine health issues the industry faces. Currently available vaccines Currently in the United States among 4 vaccine manufacturers, there are 30 licensed swine influe