Intranasal IgG4/7 antibody responses protect horses against equid herpesvirus-1 (EHV-1) infection including nasal virus shedding and cell-associated viremia

Virology. 2019 May:531:219-232. doi: 10.1016/j.virol.2019.03.014. Epub 2019 Mar 22.

Abstract

Equid herpesvirus-1 (EHV-1) outbreaks continue despite widely used vaccination. We demonstrated previously that an ORF1/ORF71 gene deletion mutant of the EHV-1 strain Ab4 (Ab4ΔORF1/71) is less virulent than its parent Ab4 virus. Here, we describe the Ab4 challenge infection evaluating protection induced by the Ab4ΔORF1/71 vaccine candidate. Susceptible control horses developed respiratory disease, fever, nasal shedding, and viremia. Full protection after challenge infection was observed in 5/5 previously Ab4 infected horses and 3/5 Ab4ΔORF1/71 horses. Two Ab4ΔORF1/71 horses developed short-lasting viremia and/or virus shedding. Protective immunity in the respiratory tract was characterized by pre-existing EHV-1-specific IgG4/7 antibodies, the absence of IFN-α secretion and rapidly increasing IgG4/7 upon challenge infection. Pre-existing systemic EHV-1-specific IgG4/7 highly correlated with protection. T-cell immunity was overall low. In conclusion, protective immunity against EHV-1 infection including prevention of viremia was associated with robust systemic and intranasal IgG4/7 antibodies suggesting immediate virus neutralization at the local site.

Keywords: Antibody; Chemokine; EHV-1; Horse; Mucosal immunity; ORF1; ORF71; Protection; T-cell immunity; Type I interferon.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Viral / immunology*
  • Female
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / prevention & control
  • Herpesviridae Infections / veterinary*
  • Herpesviridae Infections / virology
  • Herpesvirus 1, Equid / drug effects
  • Herpesvirus 1, Equid / genetics
  • Herpesvirus 1, Equid / immunology*
  • Herpesvirus 1, Equid / physiology
  • Herpesvirus Vaccines / administration & dosage*
  • Herpesvirus Vaccines / immunology
  • Horse Diseases / immunology
  • Horse Diseases / prevention & control*
  • Horse Diseases / virology
  • Horses
  • Immunoglobulin G / immunology*
  • Male
  • Nasal Mucosa / immunology
  • Nasal Mucosa / virology
  • Vaccination
  • Viremia / immunology
  • Viremia / prevention & control
  • Viremia / veterinary*
  • Viremia / virology
  • Virus Shedding

Substances

  • Antibodies, Viral
  • Herpesvirus Vaccines
  • Immunoglobulin G