CAREER: Selective sweep of plasma cell specificity following vaccination

University Of Massachusetts, Dartmouth, North Dartmouth MA

Investigators

Abstract

Vaccines have been responsible for improvements in human health, but they also have been vital for improving the health of domesticated and farmed animals. Vaccines work by administering a pathogen in a non-infectious form, which allows the animal to develop a pool of B-cells and T-cells with receptors specific for that pathogen. These pathogen-specific immune cells are retained for many years (immunological memory), and upon exposure to the real pathogen, they are ready to effectively combat and neutralize the threat. Mammals actively regulate the vaccine response, allowing only 1-2% of the adaptive immune cells to be specific for any given target. This allows mammals to be protected against many pathogens simultaneously. In contrast, when rainbow trout are vaccinated they direct 40-60%, and in some cases >90%, of their B-cells to the vaccine. This dramatic, and unexpected, response comes at the expense of all other B-cell specificities which are lost from the animal. This "all-in" response to vaccination may have long-term consequences for the health of the animal, as memory to other pathogens may have been lost. This project will investigate the B-cell responses in vaccinated rainbow trout across 3 levels of organization (cells, proteins, and genes). We are expecting to find that even though the proteins may have a singular specificity, the genes that encode for the protein will maintain considerable diversity. Discoveries made in this grant may aid in the development of vaccine strategies to improve the health of vaccinated rainbow trout which are grown on farms or released to restock our waterways. The project provides research experiences for high school and undergraduate students, and considerable research training opportunities for graduate students. The project also seeks to foster long-term educational relationships with the local community through numerous outreach initiatives.