*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
- It has been demonstrated that horses can produce BSA-specific IgE
following vaccination and this may contribute to the presence of
BSA-specific IgE in commercial plasma products.
- Neonatal foals receiving CPC supplementation within 24 hours of birth
may be at risk of developing an adverse reaction to plasma transfusion
if BSA-specific IgE is present in the administered plasma product.
- Veterinarians should follow all label recommendations for USDA
licensed Ig products, specifically including avoidance of
administering multiple products to neonatal foals.
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