B Cells Carrying Antigen Receptors Against Microbes as Tools for Vaccine Discovery and Design
Can basic science improve the art of vaccinology? Here, we review efforts to understand immune responses with the aim to improve vaccine design and, eventually, to predict the efficacy of human vaccine candidates using the tools of transformed B cells and
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Contents 1 2
Introduction.......................................................................................................................... Recurrent Clonotypes .......................................................................................................... 2.1 From BnAb Sequences to “Germline” BnAb B Cells .............................................. 3 B Cell Tumor Models for the Candidate Vaccine Antigen Response............................... 4 Immunoglobulin Transgenic and Knock-in Mice for Vaccine Research........................... 4.1 Knock-in Mice............................................................................................................ 4.2 Nuclear Transfer Mice................................................................................................ 5 Hu/SCID Mice in Vaccine Research .................................................................................. 5.1 Mice and Rats Carrying the Full Complement of Human Ig Genes ........................ References ..................................................................................................................................
Abstract Can basic science improve the art of vaccinology? Here, we review efforts to understand immune responses with the aim to improve vaccine design and, eventually, to predict the efficacy of human vaccine candidates using the tools of transformed B cells and targeted transgenic mice carrying B cells with antigen receptors specific for microbes of interest.
1 Introduction Vaccinology is, and has always been, a crucial field for public health and for basic research. Early vaccine studies led to the discovery of antibodies, which were identified by their ability to neutralize microbial toxins upon passive transfer to naive animals. While some well-known vaccines are capable of eradicating important D. Bhullar D. Nemazee (&) Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Rd, IM29, La Jolla, CA 92037, USA e-mail: [email protected] Current Topics in Microbiology and Immunology https://doi.org/10.1007/82_2019_156 © Springer Nature Switzerland AG 2019
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D. Bhullar and D. Nemazee
human pathogens, we lack adequate vaccines for many, perhaps most, human pathogens. For these challenging pathogens, the classical empirical approach to vaccinology fails, necessitating better knowledge of the microbes and the basic science of successful immune responses. When a vaccine does not work, it is often difficult to determine the reason. Basic studies in B cell biology can have an impact on finding a way forward. One facet of this approach is in the discovery of good vaccine targets. The isolation of neutralizing antibodies derived from the B cells of infected patients through the use of methodologies such as phage display, hybridoma technology, and single-cell antibody gene cloning has identified crucial epitopes toward which one can focus vaccine responses. As described in the accompanying chapter by Dennis Burton and colleagues, this
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