Immune modulation and vaccine development
Staphylococcus aureus is a common cause of mastitis, a disease estimated to cost the US dairy industry around $2 billion per year but, currently, there are no effective vaccines. Current control of S. aureus infections include proper milking time procedures and segregation or culling of infected animals. However, despite these management practices, S. aureus is still a major cause of intramammary infections in dairy cows and evades antibiotic therapies. In humans, S. aureus causes a variety of infections that are susceptible to antibiotic treatment. However the emergence of antibiotic resistant strains is a major concern for the success of future therapeutics. Consequently, there is an urgent need to develop an efficacious vaccine capable of inducing protection against S. aureus infections.
One of the main goals of Dr. Isis Kanevsky-Mullarky’s research program is to boost immune responses and enable resistance or clearance of infections. Her research program is focused on identifying the mechanisms by which infectious pathogens impair host defenses and establish infections. In addition, the group is evaluating the enhancement of the immune function to improve disease resistance. Understanding mechanisms of host immune cell activation will aid the treatment of infections and lead to a significant improvement in both animal and human health.
To date, results from the Kanevsky laboratory have established basic mechanisms of cellular immunity in the mammary gland. The initial steps of the host response to a pathogen involve dendritic cells, which are responsible for pathogen recognition and subsequent immune responses. Previous graduate students established the presence of dendritic cells; cells critical to the initiation of a protective immune response against infection in the bovine mammary gland. These findings laid the groundwork for the continued use of these cell types in immune modulation during vaccine development against S. aureus. Subsequent student findings show the existence of S. aureus specific immune (CD4+ and CD8+) memory cell populations in the blood of cows previously infected with S. aureus mastitis. These results pave the way for the identification of key protein antigens (immune epitopes) that can be used in the development of a novel and efficacious vaccine against S. aureus infections. Ongoing challenge studies using live and modified S. aureus are focused on modulation of T cell profiles in the mammary gland during infection. Specific studies are underway characterizing the T cell profiles in milk after primary and secondary challenges. Together, these studies have the potential to significantly advance the efforts towards vaccine development against antibiotic-resistant S. aureus strains in both animal and human populations by incorporating a bovine rather than a murine model for the identification of natural vaccine antigens.
Developing and Supporting Projects
Vaccination is only one of the means by which immune function can be enhanced. The Kanevsky laboratory, in collaboration with a variety of partners, is working on a) identification of the mechanisms by which a bovine feed additive enhances immune cell function using a mouse model, b) study of bacterial modifications on immune cell function in murine models of lung infections, and c) the role of lymphocytes in the development of neonatal immune function and development.
The recent studies of neonatal immune function in the Kanevsky laboratory were driven by a Masters degree student interested in calf development, nutrition, and immunity. The ingestion of colostrum, the first milk of the mammary gland after calving, provides nutrition and stimulation of immune development to the neonate. To date, passive transfer of immunoglobulins (antibodies) has been the main criteria for determining colostrum quality. However, colostrum also contains hormones, proteins and vitamins, cytokines (immune-enhancing proteins), anti-bacterial proteins, and viable immune cells. Data from a recent trial indicated enhanced response to vaccination in heifers fed whole as compared to cell-free colostrum at birth. These studies are aimed at determining the role of maternal immune cells on enhancing innate and adaptive immune function in the calf. Current studies will continue to target vaccine and colostrum management strategies at improving transfer of maternal cells to enhance neonatal disease resistance and immune development
Overall, the ability to raise animals with a stronger immune system will allow for less disease during the lifespan of the animal and therefore a reduced economic cost to dairy producers due to fewer veterinary bills and losses of animals. Defining the role played by immune cells both during mucosal infections, such as mammary and lung, as well as neonatal immune development will help identify new biology to reduce disease and death in dairy animals.