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A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model
Institution:1. Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA;2. Institute for Immunology and Informatics, Department of Cell and Molecular Biology, University of Rhode Island, Providence, RI, USA;3. Animal Science, School of Environmental and Rural Science, University of New England, Armidale, Australia;4. EpiVax Inc., Providence, RI, USA;5. The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, UK;1. Department of General Chemistry, Belarusian State Medical University, Dzerzinskogo 83, Minsk, Belarus;2. Biochemical Group of the Multidisciplinary Diagnostic Laboratory, Institute of Physiology of the National Academy of Sciences of Belarus, Academicheskaya 28, Minsk, Belarus;3. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory 1-40, Moscow, 119991, Russia;1. Surgery Service, Transplant Unit, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain;2. Biomedical Research Institute of Murcia (IMIB-Arrixaca), University of Murcia, Murcia, Spain;3. International Collaborative Donor Project, Murcia, Spain;4. Department of Animal Production, Faculty of Veterinary, University of Murcia, Murcia, Spain;5. Grupo Fisiopatología de la Reproducción, Departamento Producción y Sanidad Animal, Salud Pública Veterinaria y Ciencia y Tecnología de los Alimentos, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities Valencia, Valencia, Spain;6. Escola de Veterinária e Zootecnia, Universidade Federal de Goiás, Goiania, Brazil;7. Endocrinology and Nutrition Service, Hospital Clínico, Universitario Virgen de la Arrixaca, Murcia, Spain;1. OIE Reference Laboratory for Swine Influenza, Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Via Dei Mercati 13A, 43126 Parma, Italy;2. Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Via Pitagora 2, 42124 Reggio Emilia, Italy;3. Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, Virologia Via A, Bianchi 9, 25125 Brescia, Italy;4. DVM, Via Adige 60, 36100 Vicenza, Italy;1. Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul 08826, Republic of Korea;2. BioApplications Inc., Pohang Techno Park Complex, 394 Jigok-ro, Nam-gu, Pohang 37668, Republic of Korea;1. Vaccinology & Immunotherapeutic Program, School of Public Health at the University of Saskatchewan, Canada;2. Vaccine & Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Canada
Abstract:Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.
Keywords:Influenza A virus  Pigs  DNA vaccine  Prime boosting  Intradermal vaccination  T cell epitope  Immunoinformatics  CMI"}  {"#name":"keyword"  "$":{"id":"k0045"}  "$$":[{"#name":"text"  "_":"cell mediated immunity  EDV"}  {"#name":"keyword"  "$":{"id":"k0055"}  "$$":[{"#name":"text"  "_":"epitope driven vaccine  HA"}  {"#name":"keyword"  "$":{"id":"k0065"}  "$$":[{"#name":"text"  "_":"hemagglutinin  IAV"}  {"#name":"keyword"  "$":{"id":"k0075"}  "$$":[{"#name":"text"  "_":"influenza A virus  NA"}  {"#name":"keyword"  "$":{"id":"k0085"}  "$$":[{"#name":"text"  "_":"neuraminidase  PBMCs"}  {"#name":"keyword"  "$":{"id":"k0095"}  "$$":[{"#name":"text"  "_":"peripheral blood mononuclear cells  PBS"}  {"#name":"keyword"  "$":{"id":"k0105"}  "$$":[{"#name":"text"  "_":"phosphate buffered saline  pH1N1"}  {"#name":"keyword"  "$":{"id":"k0115"}  "$$":[{"#name":"text"  "_":"pandemic H1N1  PSI"}  {"#name":"keyword"  "$":{"id":"k0125"}  "$$":[{"#name":"text"  "_":"pounds per square inch  SLA"}  {"#name":"keyword"  "$":{"id":"k0135"}  "$$":[{"#name":"text"  "_":"swine leukocyte antigen
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