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Vaccination-challenge studies with a Port Chalmers/73 (H3N2)-based swine influenza virus vaccine: Reflections on vaccine strain updates and on the vaccine potency test
Affiliation:1. Federal University of Rio Grande do Sul/UFRGS, Porto Alegre, RS, Brazil;2. Embrapa Swine and Poultry, Concórdia, SC, Brazil;1. Epidemiology Unit, Preventive Veterinary Medicine Department, Faculty of Veterinary Sciences, University of Chile, Chile;2. Comparative Biomedical Science Program, School of Veterinary Medicine, University of Wisconsin-Madison, United States;3. Department of Infectious Diseases, St. Jude Children''s Research Hospital, United States;1. Virus and Prion Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, 1920 Dayton Avenue, Ames, IA 50010, USA;2. Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, K-221 Mosier Hall, Manhattan, KS 66506, USA;3. Istituto Zooprofilattico Sperimentale dell’Abruzzo e Molise “G. Caporale”, Teramo, Italy;4. University of Minnesota Veterinary Diagnostic Laboratory, 1333 Gortner Avenue, St. Paul, MN 55108, USA;5. Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK;6. Department of Biology, Georgia Southern University, P.O. Box 8042-1, Statesboro, GA 30460, USA;1. Department of Biology, Georgia Southern University, Statesboro, GA, USA;2. Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, Ames, IA, USA;3. Fogarty International Center, National Institutes of Health, Bethesda, MD, USA;4. School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA;5. Department of Zoology, University of Cambridge, Cambridge, United Kingdom;6. National Veterinary Services Laboratories, USDA-APHIS-VS-STAS, Ames, IA, USA
Abstract:
The human A/Port Chalmers/1/73 (H3N2) influenza virus strain, the supposed ancestor of European H3N2 swine influenza viruses (SIVs), was used in most commercial SIV vaccines in Europe until recently. If manufacturers want to update vaccine strains, they have to perform laborious intratracheal (IT) challenge experiments and demonstrate reduced virus titres in the lungs of vaccinated pigs. We aimed to examine (a) the ability of a Port Chalmers/73-based commercial vaccine to induce cross-protection against a contemporary European H3N2 SIV and serologic cross-reaction against H3N2 SIVs from Europe and North America and (b) the validity of intranasal (IN) challenge and virus titrations of nasal swabs as alternatives for IT challenge and titrations of lung tissue in vaccine potency tests. Pigs were vaccinated with Suvaxyn Flu® and challenged by the IT or IN route with sw/Gent/172/08. Post-vaccination sera were examined in haemagglutination-inhibition assays against vaccine and challenge strains and additional H3N2 SIVs from Europe and North America, including an H3N2 variant virus. Tissues of the respiratory tract and nasal swabs were collected 3 days post challenge (DPCh) and from 0–7 DPCh, respectively, and examined by virus titration. Two vaccinations consistently induced cross-reactive antibodies against European H3N2 SIVs from 1998–2012, but minimal or undetectable antibody titres against North American viruses. Challenge virus titres in the lungs, trachea and nasal mucosa of the vaccinated pigs were significantly reduced after both IT and IN challenge. Yet the reduction of virus titres and nasal shedding was greater after IT challenge. The Port Chalmers/73-based vaccine still offered protection against a European H3N2 SIV isolated 35 years later and with only 86.9% amino acid homology in its HA1, but it is unlikely to protect against H3N2 SIVs that are endemic in North America. We use our data to reflect on vaccine strain updates and on the vaccine potency test.
Keywords:H3N2 swine influenza virus  Europe  North America  Antigenic evolution  Swine influenza virus vaccine potency test  Vaccine strain selection
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