Protection of pigs against pandemic swine origin H1N1 influenza A virus infection by hemagglutinin- or neuraminidase-expressing attenuated pseudorabies virus recombinants

Virus Res. 2015 Mar 2:199:20-30. doi: 10.1016/j.virusres.2015.01.009. Epub 2015 Jan 17.

Abstract

Influenza is an important respiratory disease of pigs, and may lead to novel human pathogens like the 2009 pandemic H1N1 swine-origin influenza virus (SoIV). Therefore, improved influenza vaccines for pigs are required. Recently, we demonstrated that single intranasal immunization with a hemagglutinin (HA)-expressing pseudorabies virus recombinant of vaccine strain Bartha (PrV-Ba) protected pigs from H1N1 SoIV challenge (Klingbeil et al., 2014). Now we investigated enhancement of efficacy by prime-boost vaccination and/or intramuscular administration. Furthermore, a novel PrV-Ba recombinant expressing codon-optimized N1 neuraminidase (NA) was included. In vitro replication of this virus was only slightly affected compared to parental virus. Unlike HA, the abundantly expressed NA was efficiently incorporated into PrV particles. Immunization of pigs with the two PrV recombinants, either singly or in combination, induced B cell proliferation and the expected SoIV-specific antibodies, whose titers increased substantially after boost vaccination. After immunization of animals with either PrV recombinant H1N1 SoIV challenge virus replication was significantly reduced compared to PrV-Ba vaccinated or naïve controls. Protective efficacy of HA-expressing PrV was higher than of NA-expressing PrV, and not significantly enhanced by combination. Despite higher serum antibody titers obtained after intramuscular immunization, transmission of challenge virus to naïve contact animals was only prevented after intranasal prime-boost vaccination with HA-expressing PrV-Ba.

Keywords: Attenuated PrV strain Bartha; Hemagglutinin (HA); Neuraminidase (NA); Pandemic H1N1 SoIV; Vectored vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / blood
  • B-Lymphocytes / immunology
  • Base Sequence
  • Disease Transmission, Infectious / prevention & control
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Herpesvirus 1, Suid / genetics
  • Herpesvirus 1, Suid / growth & development*
  • Immunophenotyping
  • Influenza A Virus, H1N1 Subtype / growth & development*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Injections, Intramuscular
  • Molecular Sequence Data
  • Neuraminidase / genetics
  • Neuraminidase / immunology*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • Orthomyxoviridae Infections / transmission
  • Orthomyxoviridae Infections / veterinary*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Swine
  • Swine Diseases / immunology
  • Swine Diseases / prevention & control*
  • Swine Diseases / transmission
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Recombinant Proteins
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • Viral Proteins
  • NA protein, influenza A virus
  • Neuraminidase