Principal Investigator: Sarah Caddy

DESCRIPTION (provided by applicant): 

Neonatal puppies are highly susceptible to infection as their immune responses are still developing. To support this period of immunodeficiency, maternal antibodies (MA) are delivered to pups from the mother across the placenta and in colostrum. Insufficient MA delivery can result in higher pup mortality, and therefore it is essential that optimal delivery is achieved.

Groundbreaking work has recently shown the human placenta and breast tissue act like a sieve, selectively transferring only the most valuable antibodies to the infant. Antibodies able to activate NK cells are specifically transferred across the placenta in humans, associated with expression of a specific glycan and antibody receptor binding profile. Similarly, antibodies stimulating phagocytosis are preferentially secreted into human breastmilk. It is known that MA transfer mechanisms in dogs are not the same as humans, as dogs have a more complex placenta and the composition of colostrum is different. However, whether selective transfer of MA can also occur in dogs has never previously been studied. If it can be shown that specific subsets of canine antibodies are preferentially transferred, then strategies to boost these by maternal vaccination could result in enhanced antibody delivery to pups.

We aim to characterize the canine antibodies that are transported from the maternal circulation into the umbilical cord and colostrum, and determine whether selective transfer of antibodies with specific functions occurs. To achieve this we will collect samples from dogs undergoing caesarean section in the Theriogenology Service at the Cornell University Hospital for Animals. Antibodies in the mothers blood, cord blood and colostrum will be analyzed in detail using a panel of canine-specific antibody assays we will develop to measure a wide range of biophysical and functional characteristics. We predict that there will be key differences between antibodies in maternal blood and antibodies delivered to the neonate, representing selective transfer of antibodies with key biological effects. We anticipate that this project will lead to development of future strategies to enhance MA transfer to pups and therefore improve neonatal survival.