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

Grants and funding

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/).