Cellular Screens to Interrogate the Human T and B Cell Repertoires and Design Better Vaccines
Jens Wrammert and Kaja Murali-Krishna
from: Advanced Vaccine Research Methods for the Decade of Vaccines (Edited by: Fabio Bagnoli and Rino Rappuoli). Caister Academic Press, U.K. (2015) Pages: 133-156.
The success of vaccines depends upon their ability to induce memory T cells, B cells and long lasting antibody secreting plasma cells. These memory cells differ in quantity, quality, homing characteristics and persistence depending upon vaccine antigen, adjuvants and delivery systems. A thorough understanding of the receptor repertoire associated with protective immunity, and in some cases infection-driven pathology, or in situations such as autoimmunity, cancer, allergy or transplant rejection, is important for rational design of vaccines and therapeutics. In this chapter we will first briefly introduce general processes involved in the generation of naïve T and B cell receptor repertoire and the complex functional changes that can occur in these cells when they encounter antigen. Following this, we will discuss recent progress in the development of novel tools for B and T-cell receptor repertoire analysis combined with cellular states and functions. The concurrent development of genomics and detailed functional analyses, both on a global as well as at a single cell level, also allows us to gain additional insight into the mechanisms of immunological memory. Together, these cellular screens allow defining optimal antigens and adjuvants and ultimately enable the development of more efficacious vaccines read more ...