Discovery will be a boon in fine-tuning vaccination schedules for foals

Dr Julia Felippe works in her lab. Photo: Elodie Gazave
Dr Julia Felippe works in her lab. Photo: Elodie Gazave

Researchers have discovered a new way to measure tiny amounts of antibodies in foals, which will help optimize vaccination schedules and help our understanding of how early these youngsters start bolstering their own immune system.

The findings by researchers at Cornell University’s College of Veterinary Medicine have been reported in the open-access peer-reviewed journal PLOS ONE.

Newborn horses are initially protected against diseases by antibodies they receive after birth through the colostrum produced by their mother.

Vaccination is an important strategy to protect these youngsters against diseases. However, giving them too early in life may have negative effects. Vaccines work by presenting the immune system with a killed pathogen (or a protein from it) that will “train” the body to recognize it as an intruder.

If the immune system of the young animal is not ready, instead of recognizing the pathogen’s protein in the vaccine as foreign, it may identify it as “self” and impair the production of an immune response against this particular pathogen.

Additionally, the mother’s antibodies may interfere with the newborn’s antibody production, making the vaccine ineffective.

To develop a protective vaccination strategy, it is crucial to understand how young animals become immunocompetent.

Dr Julia Felippe, associate professor of large animal medicine at the veterinary college, and research associate Rebecca Tallmadge say the new method they developed will help our understanding of how fast a foal starts producing its own antibodies, which in turn will help optimize recommendations for young-horse vaccination schedules.

Monitoring the development the immune system of newborn foals using traditional methods, such as an antibody count in the foal’s blood, is hampered by the abundance of maternal antibodies relative to the young’s own.

The maternal antibodies wear off progressively as the young animal ages, but this may take a few months depending on the half-life of the different antibodies.

Current guidelines recommend vaccination of foals to start at 3 months or at 6 months of age if the dam was vaccinated in late gestation.

“We presume that if the mother is vaccinated in her last month of pregnancy, her antibodies will transfer to the foal, but in reality we don’t measure the efficiency of this process,” explains Felippe.

Previous work led Felippe and Tallmadge to believe that the foal immune system could respond to vaccines very early in life, and the team decided to test this hypothesis.

They vaccinated 3-day-old foals, gave them boosters at 21 and 35 days, and followed the foals’ immune response up to 42 days after birth.

Research associate Rebecca Tallmadge, left, and Dr Julia Felippe, associate professor of large animal medicine. Photo: Elodie Gazave
Research associate Rebecca Tallmadge, left, and Dr Julia Felippe, associate professor of large animal medicine. Photo: Elodie Gazave

To overcome the challenge of counting antibodies in such young foals, Felippe and Tallmadge examined the foals’ B cells – the cells that create antibodies. This allowed them to examine the foal’s immune response alone, independent of maternal circulating antibodies.

Additionally, B cells take up to 10 days before releasing the antibodies they created.

“After they find a match for the antibody, B cells adjust and tweak their antibody to make a perfect fit for the pathogen,” says Felippe. “They are amazing, they are like little factories.”

The DNA changes that occur in the B cells’ maturation process can thus be tracked through time by sequencing their DNA.

As the researchers gave boosters to the foals, they observed an increase in the diversity of mutations in the B cell DNA as those immune cells kept looking for a better fit to the antigen.

“Testing antigen-specific B cells gave us beautiful responses,” says Tallmadge. This suggests that foals start producing antibodies in the first days when vaccinated. Yet results were different depending on the type of vaccine.

“Our results suggested that some vaccines may induce higher production of antibodies than others,” adds Felippe. “However, our experiment was not designed to measure efficacy of certain vaccines.” Rather, its aim was to explore the neonate’s immune response almost in real time, and with more sensitivity, without confounding circulating maternal antibodies.

Tallmadge continues: “Our approach can be applied to any vaccine or pathogen in any host species.

After showing that newborns are capable of an immune response, the researchers now want to see if there are newborn-specific mechanisms designed to prevent this response.

Felippe: “The reason why such a mechanism would exist is, imagine you live in the womb, very protected, and now you are out in the environment with billions of pathogens poking you for an immune response. If you respond to every stimulus with the same intensity at the same time, something might happen with you.

“So, there may be something out there that prevents you from damaging yourself in this process and prioritizes a response to a stimulus that is relevant.”

Tallmadge RL, Miller SC, Parry SA, Felippe MJB (2017) Antigen-specific immunoglobulin variable region sequencing measures humoral immune response to vaccination in the equine neonate. PLoS ONE 12(5): e0177831.

Reporting: Elodie Gazave

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