DNA vaccine based on conserved HA-peptides induces strong immune response and rapidly clears influenza virus infection from vaccinated pigs

Autoři: Marta Sisteré-Oró aff001;  Sergi López-Serrano aff001;  Veljko Veljkovic aff002;  Sonia Pina-Pedrero aff001;  Júlia Vergara-Alert aff001;  Lorena Córdoba aff001;  Mónica Pérez-Maillo aff001;  Patrícia Pleguezuelos aff001;  Enric Vidal aff001;  Joaquim Segalés aff003;  Jens Nielsen aff005;  Anders Fomsgaard aff005;  Ayub Darji aff001
Působiště autorů: IRTA, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain aff001;  Biomed Protection, Galveston, Texas, United States of America aff002;  UAB, Centre de Recerca en Sanitat Animal (CReSA, IRTA-UAB), Campus de la Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain aff003;  Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, UAB, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain aff004;  Virus Research and Development Laboratory, Department of Virus and Microbiological Special Diagnostics, Statens Serum Institut, Artillerivej, Copenhagen S, Denmark aff005
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222201


Swine influenza virus (SIVs) infections cause a significant economic impact to the pork industry. Moreover, pigs may act as mixing vessel favoring genome reassortment of diverse influenza viruses. Such an example is the pandemic H1N1 (pH1N1) virus that appeared in 2009, harboring a combination of gene segments from avian, pig and human lineages, which rapidly reached pandemic proportions. In order to confront and prevent these possible emergences as well as antigenic drift phenomena, vaccination remains of vital importance. The present work aimed to evaluate a new DNA influenza vaccine based on distinct conserved HA-peptides fused with flagellin and applied together with Diluvac Forte as adjuvant using a needle-free device (IntraDermal Application of Liquids, IDAL®). Two experimental pig studies were performed to test DNA-vaccine efficacy against SIVs in pigs. In the first experiment, SIV-seronegative pigs were vaccinated with VC4-flagellin DNA and intranasally challenged with a pH1N1. In the second study, VC4-flagellin DNA vaccine was employed in SIV-seropositive animals and challenged intranasally with an H3N2 SIV-isolate. Both experiments demonstrated a reduction in the viral shedding after challenge, suggesting vaccine efficacy against both the H1 and H3 influenza virus subtypes. In addition, the results proved that maternally derived antibodies (MDA) did not constitute an obstacle to the vaccine approach used. Moreover, elevated titers in antibodies both against H1 and H3 proteins in serum and in bronchoalveolar lavage fluids (BALFs) was detected in the vaccinated animals along with a markedly increased mucosal IgA response. Additionally, vaccinated animals developed stronger neutralizing antibodies in BALFs and higher inhibiting hemagglutination titers in sera against both the pH1N1 and H3N2 influenza viruses compared to unvaccinated, challenged-pigs. It is proposed that the described DNA-vaccine formulation could potentially be used as a multivalent vaccine against SIV infections.

Klíčová slova:

Antibodies – Enzyme-linked immunoassays – Fevers – Influenza viruses – Swine – Vaccination and immunization – Vaccines – Flagellin


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