Neonatal Immunization with a Single IL-4/Antigen Dose Induces Increased Antibody Responses after Challenge Infection with Equine Herpesvirus Type 1 (EHV-1) at Weanling Age

PLoS One. 2017 Jan 3;12(1):e0169072. doi: 10.1371/journal.pone.0169072. eCollection 2017.

Abstract

Neonatal foals respond poorly to conventional vaccines. These vaccines typically target T-helper (Th) cell dependent B-cell activation. However, Th2-cell immunity is impaired in foals during the first three months of life. In contrast, neonatal basophils are potent interleukin-4 (IL-4) producers. The purpose of this study was to develop a novel vaccine triggering the natural capacity of neonatal basophils to secrete IL-4 and to evaluate if vaccination resulted in B-cell activation and antibody production against EHV-1 glycoprotein C (gC). Neonatal vaccination was performed by oral biotinylated IgE (IgE-bio) treatment at birth followed by intramuscular injection of a single dose of streptavidin-conjugated gC/IL-4 fusion protein (Sav-gC/IL-4) for crosslinking of receptor-bound IgE-bio (group 1). Neonates in group 2 received the intramuscular Sav-gC/IL-4 vaccine only. Group 3 remained non-vaccinated at birth. After vaccination, gC antibody production was not detectable. The ability of the vaccine to induce protection was evaluated by an EHV-1 challenge infection after weaning at 7 months of age. Groups 1 and 2 responded to EHV-1 infection with an earlier onset and overall significantly increased anti-gC serum antibody responses compared to control group 3. In addition, group 1 weanlings had a decreased initial fever peak after infection indicating partial protection from EHV-1 infection. This suggested that the neonatal vaccination induced a memory B-cell response at birth that was recalled at weanling age after EHV-1 challenge. In conclusion, early stimulation of neonatal immunity via the innate arm of the immune system can induce partial protection and increased antibody responses against EHV-1.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies, Viral / blood
  • Antibody Formation
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology
  • Cytokines / immunology
  • Herpesviridae Infections / prevention & control
  • Herpesviridae Infections / veterinary*
  • Herpesvirus 1, Equid*
  • Herpesvirus Vaccines / therapeutic use*
  • Horse Diseases / prevention & control*
  • Horse Diseases / virology
  • Horses / immunology*
  • Interleukin-4 / administration & dosage
  • Interleukin-4 / immunology
  • Lymphocyte Activation
  • Neutralization Tests / veterinary
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / immunology
  • Temperature
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / immunology

Substances

  • Antibodies, Viral
  • Cytokines
  • Herpesvirus Vaccines
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • glycoprotein C, Equid herpesvirus 1
  • Interleukin-4

Grant support

Funding for this project was provided by the Harry M. Zweig Memorial Fund for Equine Research at Cornell University ‘A Novel Strategy to Boost Antibody Production to EHV-1 in Neonates’ (http://vet.cornell.edu/research/Zweig/). Monoclonal antibody development for horse cell surface markers and cytokines was supported by USDA grant #2005-01812 ‘The US Veterinary Immune Reagent Network’ and #2015-67015-23072 ‘Equine Immune Reagents: Development of monoclonal antibodies to improve the analysis of immunity in horses’ (https://nifa.usda.gov/).