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.