Comparison among all samples
Figure 4 provides a comparison of mean OD values for BSA-specific IgE among all samples that were tested. The index case serum at 12 hours of age and unvaccinated horses were among the lowest values measured. Healthy horses and commercial plasma donor horses’ values were intermediate. The highest values were observed from reactor horses and the commercial plasma sample administered to the index case.
DISCUSSION
Data from the current investigation as well as from previous work demonstrate that horses express BSA-specific IgE following routine vaccination. These findings are consistent with post-vaccination studies in both humans (Hardefeldt et al. 2010; Silva et al. 2017) and horses (Loughney et al. 2014). As expected, horses that had never been vaccinated did not demonstrate notable levels of BSA-specific IgE. Among horses tested, the younger age group (3-9 years of age) had more horses displaying a greater than 1.5-fold increase in BSA-specific IgE at 2 weeks post-vaccination compared to baseline. This suggests that younger horses develop a greater immune response to BSA than older horses. Forty-six of the 65 healthy horses demonstrated an increase in BSA-specific IgE during at least one time point after vaccination compared to baseline. Sixteen of the 65 healthy horses showed a greater than 1.5-fold increase in BSA-specific IgE at 14 days post-vaccination compared to baseline. Six of these 16 horses had a greater than 4-fold increase in BSA-specific IgE at 14 days post-vaccination. All of these 6 horses were between 3 and 11 years of age. Interestingly, none of these 65 horses developed clinical signs associated with an adverse vaccine reaction. This is suggestive that the presence of BSA-specific IgE or the rise in BSA-specific IgE does not directly correlate with the development of an adverse vaccine reaction, which is consistent with the previous report from Gershwin et al. (2012).
Horses that had either historically or currently experienced an immediate severe adverse vaccine reaction all had detectable levels of BSA-specific IgE on ELISA. The majority of these horses had blood samples collected within 24 hours post-vaccination. Ten out of the 12 reactor horse samples at 24 hours post-vaccination had an BSA-specific IgE OD value greater than 0.200 (83.3%). Whereas only 9 out of the 65 healthy horses had an BSA-specific IgE OD value greater than 0.200 at 14 days post-vaccination (13.8%). Twenty-four-hour post-vaccination blood samples from horses not experiencing a vaccine reaction could be investigated by ELISA to determine a reference interval for BSA-specific IgE in healthy horses. A very small subset of these reactor horses had blood samples from 180- and 270-days post-vaccination. While their BSA-specific IgE levels appeared to be higher than the healthy horses in this study, these values were not statistically different from healthy horses. A larger sample of horses is needed in order to further investigate whether reactor horses have a significantly increased BSA-specific IgE level at different time points post-vaccination. With this information, horses developing a vaccine reaction could be tested in order to determine if they have elevated BSA-specific IgE levels. With reference intervals available, it could be possible to screen horses prior to vaccination to determine if they are at a higher risk for developing a vaccine reaction specifically against BSA.
Horses used as commercial plasma donors had BSA-specific IgE levels similar to healthy, non-reactor horses. The history of these horses was unknown. Important information would include the age of these horses, how frequently they were vaccinated, when their last vaccine was administered and how long they had been in the program for plasma collection.
The index foal had serum collected at 12 hours of life which was analyzed for BSA-specific IgE and was similar to a non-vaccinated horse. Commercial plasma administered to the index foal was analyzed for BSA-specific IgE and was found to have higher BSA-specific IgE compared with healthy horses, commercial donor plasma or vaccine reactor horses. Based on this finding, it appears that at least an individual commercial plasma sample had elevated BSA-specific IgE levels and this could occur in other donor horses although it appears uncommon. In the described index case, the authors presume interaction of the high BSA-specific IgE administered in plasma interacted with circulating BSA absorbed from the powdered colostral product, which led to an immediate hypersensitivity and anaphylactic reaction due to mast cell degranulation and acute release of histamine and serotonin with resulting effects on the shock organs of horses: respiratory and gastrointestinal tracts.
Two commercial plasma products administered to equine neonatal patients are USDA-licensed for administration in equine neonates for the treatment of failure of transfer of passive immunity. USDA-licensed plasma1 is guaranteed to have an IgG concentration of at least 2800 mg/dL. When plasma is administered to a foal that has been exposed to BSA in commercial powdered colostrum, it has the possibility to lead to a fatal, idiosyncratic reaction as described above. Among available commercial plasma products, manufacturers1,2explicitly state that the product should not be administered to neonatal foals that have received any commercial powdered colostral or milk replacer product for this specific reason.
Further investigation is indicated to determine the frequency of elevated BSA-specific IgE among commercial plasma donor horses as well as the kinetics of administered BSA-specific IgE in foals and when or if it may be safe to administer plasma products to foals that have received powered colostral products in their first 24 hours of life. Further investigation is also warranted in larger number of reactor horses to determine if BSA-specific IgE may be predictive of adverse vaccine reactions. This study additionally brings up the practice of vaccine manufacturing using BSA and its safety.
This study supports the theory that horses can mount an immune response to BSA in vaccines by producing BSA-specific IgE. Based on the current report, there is an indication to use caution upon administration of commercial plasma to a neonate that has consumed powdered colostrum supplementation prior to complete gut closure. Collectively, USDA licensed plasma manufacturer guidelines should be followed to avoid administration of greater than any one commercial IgG supplement to neonatal foals.