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.
Authors: Wagner Bettina, Perkins Gillian, Babasyan Susanna, Freer Heather, Keggan Alison, Goodman Laura B, Glaser Amy, Torsteinsdóttir Sigurbjorg, Svansson Vilhjálmur, Björnsdóttir Sigríður
Journal: PloS one
Summary
# Editorial Summary: Neonatal IL-4 Immunisation and EHV-1 Protection in Foals Neonatal foals present a distinctive immunological challenge: their T-helper 2 (Th2) cell responses remain substantially immature during the first three months of life, rendering conventional vaccines largely ineffective at generating protective antibody responses. Wagner and colleagues exploited an alternative immunological pathway by developing a novel vaccination strategy that harnesses neonatal basophils' natural capacity to produce interleukin-4 (IL-4), a key Th2 cytokine. Foals receiving a priming dose of oral biotinylated IgE at birth followed by intramuscular injection of a streptavidin-conjugated gC/IL-4 fusion protein (targeting equine herpesvirus type 1 glycoprotein C) generated robust memory B-cell responses that remained clinically silent until EHV-1 challenge at weaning (7 months); upon infection, vaccinated groups demonstrated significantly earlier and elevated anti-gC serum antibody responses compared to controls, with the fully primed group exhibiting a reduced initial fever peak indicative of partial clinical protection. This work demonstrates that circumventing conventional Th2-dependent pathways in favour of innate immune activation represents a viable approach to neonatal foal immunisation, with potential implications for protection against EHV-1 and possibly other pathogens in very young animals where standard vaccination schedules offer limited benefit.
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Practical Takeaways
- •A novel neonatal EHV-1 vaccination strategy using IL-4 stimulation can prime immune memory at birth that provides measurable protection when foals encounter the virus at weaning—potentially addressing the immunological gap in young foals
- •Vaccinated foals mounted faster and stronger antibody responses to EHV-1 challenge and experienced milder initial disease signs, suggesting practical benefit for disease control in breeding operations
- •This approach leverages neonatal basophil IL-4 production rather than relying on the immature Th2 response, offering a mechanistically sound alternative to conventional vaccines that fail in the first months of life
Key Findings
- •Neonatal vaccination with IL-4/antigen fusion protein induced memory B-cell responses that were recalled at weaning (7 months) after EHV-1 challenge
- •Vaccinated weanlings showed significantly earlier onset and increased anti-gC serum antibody responses compared to non-vaccinated controls following EHV-1 challenge
- •Group 1 vaccinated foals demonstrated decreased initial fever peak after infection, indicating partial protection from EHV-1
- •The IL-4-based neonatal vaccine successfully stimulated immunity via the innate immune system in foals when conventional Th2-dependent vaccines fail