All of this leaves Felippe with two questions: Are we using the correct tools to measure this? And are we limiting our interpretation
to our ability of measuring the foal's response to vaccination?
"What our lab developed with Rebecca Tallmadge, the creator of the technique, was the ability to measure the foal immune response
to antigens without the confounding factor of maternally derived antibodies," Felippe says. "Tallmadge's technique measures
the immunoglobulin expressed on B cells that is being generated by the foal against that antigen."
Within the immunoglobulin is a "variable" region. This region has specificity to the antigen that is being produced against
it. Without the confounding element of the maternal antibodies, Tallmadge can measure the true production of immunoglobulins
by the foal when they are still expressed on the surface of the foal's B cells. Not only that, she can measure how well these
immunoglobulins are evolving with the boosters.
"With each round of boosters you are stimulating either the same cells or creating new cells that can bind to those antigens,
and you are creating what we call diversity in the repertoire of immunoglobulins," Felippe says. "In the end, you are going to have immunoglobulins that can bind to
any single small area on that antigen, and in a large amount of them. The efficiency in binding and neutralizing antigens
increases with the number of exposures you have to that specific antigen. So we get better immunity as we go along with the
Tallmadge can measure initially and quantitatively how much of a response a neonate can elaborate, and she can measure the
dynamics of the response over time with the boosters, without the technically confounding element of the maternal antibodies.
The development of memory cells also has been quite limited, even in the human literature. Several studies in humans discuss
the inability of the infant to respond to vaccines and the maternal antibody interference. "But, very few of these studies
address the elaboration of memory cells, which is important," says Felippe. "In some neonatal models of study, neonates are
more interested at first in producing memory than they are necessarily in producing a significant amount of immunoglobulin,
which is a differentiation of these cells into memory cells instead of plasma cells, respectively. We don't know the result
in the foal, but we are studying it. Perhaps there is a bias in the neonate in producing memory, before they can necessarily
devote the capacity to producing a high quantity of immunoglobulins. That's why they tend to increase their antibody levels
kind of gently in the beginning, and then all of a sudden they spike their antibody production. There is an interesting aspect
in the dynamics."
Next steps in research
To summarize, Felippe says her team has plenty of evidence that the horse fetus is well-prepared to face the world and respond
to antigens with antibody production. Foals have all the "machinery" to produce antibodies, including elaborated antibodies,
those antibodies that have diversity. "It's hit and go," says Felippe. "The foal will be exposed to antibodies when it hits
the ground, and it is ready to respond to them."
Now Felippe's team is trying to evaluate the maternal antibody interference phenomenon by using sequences of the variable
region of the immunoglobulins expressed on the surface of B cells as a means of, first, initiating a response to vaccination,
and, second, determining their ability to elaborate that immune response efficiently.
"So we hope to have some evidence—not confounded by maternally derived antibody levels—that the neonate can indeed respond
to vaccinations," Felippe says. "The foal might not respond to everything because some vaccines induce better immunity than
others, but it seems that it is our job to find out what makes the 'trick' and take the opportunity that the foals can elaborate
an immune response and then vaccinate accordingly."
The American Association of Equine Practitioners offers guidelines for neonatal vaccinations (http://aaep.org/vaccination_guidelines.htm) that state that it is important to note if a mare has been vaccinated during the last month of gestation. With the information
Felippe and her colleagues are gathering, those guidelines could be revised.
In Part 2, the Cornell Equine research team explains two more important factors of the development of the foal's immune system—opsonization
and the foal's defenses against R. equi.
Ed Kane, PhD, is a researcher and consultant in animal nutrition. He is an author and editor on nutrition, physiology and
veterinary medicine with a background in horses, pets and livestock. Kane is based in Seattle.
1. Secor EJ, Matychak MB, Felippe MJB. Transfer of tumour necrosis factor-alpha via colostrum to foals. Vet Rec 2012;170(2):51.
2. Tallmadge RL, McLaughlin K, Secor E, et al. Expression of essential B cell genes and immunoglobulin isotypes suggests active
development and gene recombination during equine gestation. Dev Comp Immunol 2009;33(9):1027-1038.