Principal Investigator: Tracy Stokol

Co-PI: John Parker

DESCRIPTION (provided by applicant): 

Equine herpesvirus type 1 (EHV-1) is a major pathogen of horses, causing outbreaks of abortion and respiratory and neurologic disease worldwide. Protection after vaccination is incomplete and vaccinated horses can still be infected, indicating we need better vaccine strategies. The goal of vaccination is to generate an effective immune response. Most vaccination studies have focused on modifying the virus to yield better immunity, with limited success. Here, we seek to better understand how the horse’s immune system is responding to the virus. The immune system is complex, consisting of B cells, T cells and monocytes, which co-ordinate to mount an immune response. B cells are considered the first arm of the immune response and are crucial for immunity against EHV-1. This is because B cells secrete antibodies (Abs) that recognize and bind to and neutralize virus, blocking viral entry and shedding. There are millions of B cells in horses and they secrete various Ab types (IgG, IgM, IgA) and subtypes (e.g. IgG1, IgG2a), providing tremendous diversity to the immune response. Antibodies are also complex, consisting of a light and heavy chain, both of which contain antigen recognition sequences. We know that higher concentrations of various Abs are seen in blood after EHV-1 vaccination, proof of an immune response. However, of the many different Abs that are produced, we do not know which Abs are protective. Many of these Abs may not be protective and, based on our knowledge of other viruses, protective or neutralizing Abs are produced in low numbers and may be swamped by other non-neutralizing Abs. A well-designed vaccine should steer B cells to producing more protective Abs. We currently lack knowledge of how B cells, individually or at a population level, are responding to EHV-1. Here, we propose to address this problem by sequencing the antigen recognition portions of Abs of individual B cells after vaccination with modified-live virus (MLV). By sequencing the Ab regions that bind to antigens, we can identify how the B cell population is reacting to EHV-1 and which Abs they are producing. By understanding this global B cell response, we may identify reasons for short-lived immunity to EHV-1 – a crucial step towards the design of better vaccines.