Dr. Bettina Wagner
Successful early-in-life vaccination can have a substantial impact to decrease equine herpesvirus type 1 (EHV-1) transmission and clinical disease outbreaks in the horse population. Vaccination of young foals is a challenging task because they poorly respond to existing vaccines. Approved EHV-1 vaccines are tested and optimized for the adult immune system. A neonatal vaccine likely needs to be composed differently to effectively induce immunity in young foals. We previously reported that the T-helper 2 (Th2) response, which is the major initiator of long-lasting antibody production in adults, is impaired in foals until at least six months of age (Wagner et al., Vet Res 2010). Despite obvious T-cell immaturity, antibody production occurs in very young foals and reaches adult levels by three months of age. This suggests that foals use alternative mechanisms to activate antibody production early in life. We identified an innate immune cell type (basophil) as the main producer of Th2-like responses in neonatal foals (Wagner et al., Dev Comp Immunol 2010).
In the project preceding this renewal application, we found initial proof-of-principle for our hypothesis that basophils can replace the impaired Th2 function early in the foal’s life. Neonates received our novel neonatal EHV-1 vaccine developed during the project. After EHV-1 challenge infection at weanling age, vaccinated foals had significantly lower fever, reduced clinical signs, and higher EHV-1-specific antibody responses compared to the control group.
Our hypothesis is that basophil activation and cytokine production by basophils are major pathways to induce B-cell memory and antibody production in neonatal and very young foals, leading to increased foal immunity and reduced clinical signs after infection with EHV-1.
Aim 1 is to optimize our novel neonatal vaccine for induction of immunity against EHV-1 in neonates. We will vaccinate neonates at birth (as previously) and add a booster vaccination (new) to further increase immunity and protection against EHV-1. In Aim 2, we will test how the novel vaccine influences development of memory B-cells in foals after vaccination and EHV-1 infection.
Relevancy: Severe EHV-1 outbreaks in the US continue to occur despite widely used vaccination. This emphasizes the fact that available EHV-1 vaccines are not fully protective against the current EHV-1 strains or are given too late, i.e. after EHV-1 transmission occurred. The project takes an “outside-the-box” approach to stimulate a natural innate cytokine production pathway in neonates to overcome the challenges of EHV-1 vaccination early in life. The long-term goal of this proposed project is to prevent EHV-1 transmission and infection of foals early in life thereby reducing the population of latently infected horses and future EHV-1 outbreaks.