*Corresponding author email: elizabethperrydvm@gmail.com
Keywords: horse; vaccine; plasma; IgE; bovine serum albumin
Summary
Background : Neonatal foals are born essentially agammaglobulinemic and therefore must ingest colostrum or receive immunoglobulins to maintain health. Failure of passive transfer treatment involves administration of equine colostrum, plasma or commercial powdered colostrum (CPC). Anecdotal reports suggest a risk of anaphylaxis associated with plasma transfusion in neonates that received CPC prior to gut closure. Bovine serum albumin (BSA) in CPC may serve as a target for BSA-specific immunoglobulin E (IgE) in donor equine plasma.
Objectives : To determine presence of BSA-specific IgE in samples collected post-routine vaccination in healthy horses, horses experiencing adverse vaccine reactions and commercial equine plasma.
Study Design: Prospective Observational
Methods: Serum was collected from 65 healthy horses at day 0, 14, 28, 90, 180, 270 and 365 post-vaccination, 26 horses after vaccine reaction at day 1, 180 or 270 post-vaccination, 4 horses not vaccinated and 10 horses from a commercial plasma donor herd. BSA-specific IgE was determined using enzyme-linked immunosorbent assay (ELISA).
Results : BSA-specific IgE was not detected in non-vaccinated horses and was identified in all vaccinated horses. Younger horses demonstrated higher fold changes in post-vaccination BSA-specific IgE expression compared to older horses. No significant difference in BSA-specific IgE levels between commercial plasma donors and healthy horses was identified. No significant difference in post-vaccination anti-BSA IgE levels between reactor and healthy horses at day 180 and 270 post-vaccination were identified.
Main Limitations : Small number of reactor horses at day 180 and 270 post-vaccination with most samples being collected 24 hours. There were no healthy horse samples for 24 hours post-vaccination; therefore, it was not possible to compare the two groups at this timepoint.
Conclusions : Horses may express BSA specific IgE following vaccination. There may be risk of hypersensitivity type reaction when veterinarians administer commercial plasma to neonatal foals that have consumed CPC prior to gut closure.
Clinical Relevance
INTRODUCTION
Prevention of infectious disease is an important component of maintaining equine host health. American Association of Equine Practitioner (AAEP) vaccination guidelines are available to help equine veterinarians implement safe and effective vaccine protocols (AAEP 2020). In most cases, vaccine administration results in immunologic protection against administered disease antigens with low risk to the host. In select cases, adverse reactions may occur and be associated with triggering the innate immune system and not just stimulating the adaptive, antigen-specific arm of the immune system (Tizard 2018). In a previous investigation, the etiology of allergic reactions among horses following routine vaccination was explored (Gershwin et al . 2012). Findings from this investigation revealed that vaccine-induced hypersensitivity reactions may be related to IgE responses towards non vaccine-target, culture-derived proteins (Gershwin et al . 2012). One such protein associated with this response is bovine serum albumin (BSA), the major constituent of fetal bovine serum (Gershwin et al . 2012).
Fetal bovine serum has been used for decades during vaccine manufacturing serving as an integral part of cell line cultivation. Previous work has demonstrated that BSA is associated with both milk and beef allergies in people, and there is evidence that vaccine-associated hypersensitivity reactions in people occur secondary to BSA hypersensitivities (Restani et al . 2004, Shoenfeld et al.2011, Loughney et al . 2014, Silva et al . 2017). Due to concerns for life-threatening anaphylaxis, the World Health Organization requires BSA concentration to be less than 50 ng per human vaccine dose (Loughney et al . 2014). Although used less commonly in veterinary vaccines, historically BSA was used during the manufacturing process of certain vaccines for animal use without restrictions. Evidence from the report by Gershwin et al. (2012) supports the suggestion that repeated annual or semi-annual vaccination of horses with certain vaccines could enhance the likelihood that an immune response to non-target proteins, that include BSA, could occur.
In addition to the risk for immediate hypersensitivity to non-target proteins upon vaccination, risk can exist for adverse reactions to biologic product administration sourced from hyperimmunized horses. Specifically, commercial plasma manufacturers1, 2provide a precautionary label statement that equine plasma should not be administered to neonatal foals if they received powdered colostral or milk replacer product prior to gut closure due to risk for possible hypersensitivity reaction. Foals are born agammaglobulinemic and therefore require ingestion of maternal colostrum for adequate absorption of circulating immunoglobulins, specifically IgG (Lewiset al. 2008, Felippe 2016, Tizard 2018). In cases where mare maternal colostrum is not available, commercial powdered colostral products may be administered (Gapper et al. 2007). Most commercial powdered colostral products are of bovine origin containing BSA. During the first approximately 24 hours of life, while the equine neonatal small intestine is capable of mediating absorption of intact immunoglobulins through pinocytosis, macromolecule protein absorption also takes place (Felippe 2016). In a case where a neonatal foal may ingest bovine-sourced colostral products, BSA can also be absorbed through the small intestine and enter general circulation. While previous studies have shown the administration of hyperimmune equine plasma to foals to be relatively safe (Wilson et al. 2009; Francesca et al. 2017), anecdotal reports among equine clinicians provides evidence that when foals have received powdered colostral or milk replacer products prior to gut closure and receive a subsequent plasma transfusion, unexpected and at times fatal hypersensitivity reactions have occurred. The current study reports such a case demonstrating the need for providing evidence to clinical equine veterinarians of possible adverse and even fatal outcomes in foals receiving plasma transfusions following administration of powdered colostral or milk replacers.
Anaphylaxis is a serious and potentially life-threatening reaction mediated predominately by IgE (Kalina et al. 2003; Achatzet al. 2008). Although many factors can contribute to the development of immediate hypersensitivity reactions, the primary objectives of the current study were 1) to determine if BSA-specific IgE expression occurred in healthy horses following routine annual vaccination and 2) if BSA-specific IgE expression differed in horses with reported vaccine reactions. Additionally, because commercial plasma harvested from hyperimmunized horses may contain BSA-specific IgE and commercial plasma is a commonly administered therapeutic agent in equine neonates, a secondary aim of the study was to determine BSA-specific IgE expression in commercial plasma products through testing of plasma samples from commercial plasma donors used for plasma transfusion.
MATERIALS AND METHODS