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

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.

Interleukin 4 induces rapid mucin transport, increases mucus thickness and quality and decreases colitis andCitrobacter rodentiumin contact with epithelial cells

“…IL-4 is produced by T cells, mast cells and basophils and has many biological roles in innate and adaptive immunity. Of particular relevance to the current study, IL-4 contributes to increased antibody responses after infection [49]. In the airways, IL-13 has been shown to induce mucus production via the IL-4-receptor α, Stat6 and Spdef pathway [47,48].…”

Deletion of the ORF2 gene of the neuropathogenic equine herpesvirus type 1 strain Ab4 reduces virulence while maintaining strong immunogenicity

“…Twenty-four horses from the Cornell University herd of Icelandic horses with known EHV-1 status were enrolled in this study [ 43 , 44 ]. All horses were offspring of one stallion, were born at Cornell University, and kept at an isolated facility as a group from birth.…”

“…Blood samples were collected on d-8, d-1, d1 to d14, d24, d60, d100, d130, d170, d220, and d260 pi by jugular venipuncture with a vacutainer system (20G Monoject Covidien, Medtronic Minneapolis, MN, USA) into glass tubes without anticoagulant or with sodium heparin (both BD, Franklin Lakes, NJ, USA). Serum and heparinized blood samples were processed as described previously [ 43 , 44 ].…”

“…Cell associated viremia was evaluated by real-time PCR targeting the gB gene of EHV-1 performed exactly as previously described [ 44 , 47 ]. A total of 1 × 10 7 PBMC was used for DNA extraction per horse and time point.…”

Report of the Fourth International Havemeyer Workshop on Equid Herpesviruses (EHV) EHV‐1, EHV‐2 and EHV‐5

“…Vaccines seemed able to induce cell-mediated immunity, however, as there was considerable individual variability in the responses, further work is needed to determine whether cytokine profiles can predict clinical protection. Infection of young, EHV-1 na€ ıve horses resulted in short-lived IFNc secretion by principally CD8 + PBMC [23]. Re-infection of 2-year-old horses resulted in longer lasting and more robust IFNc responses accompanied by stronger antibody responses.…”