Most vaccines provide protection by inducing the production of antibodies that can bind to a pathogen and block infection. Unfortunately, there are many dangerous viruses in which the development of a vaccine has been elusive despite decades of research. These failures highlight gaps in knowledge about the type of cell that can produce antibodies, the B cell. The Taylor lab has undertaken two approaches to help protect people from infection. In one approach, we aim to inform vaccine design by gaining a deeper understanding about the mechanisms limiting the generation of a protective B cell response. To do this, we study B cell responses in humans and murine models beginning with the rare pathogen-specific “naïve” B cells present prior to the vaccination using an enrichment method we recently developed. Our second approach is to bypass vaccination and use genetic engineering to generate B cells that produce the types of protective antibodies that vaccination aims to generate.