Regulation of Memory B cells During Vaccination

Vaccines are still lacking against genetically variable pathogens including HIV-1 and hepatitis C virus, and potent vaccines are also lacking against other viral pathogens including dengue and influenza viruses. Antibodies are the correlate of protection for most existing vaccines.

However, to protect against variable pathogens, unusual qualities of antibodies are often required, which develop over time during recall responses initiated upon repeated exposures to the antigen. The regulation of recall responses is fundamentally different to the primary adaptive immune response.

To elicit antibodies with specific qualities, my overall aim is to elucidate how B cell recall responses are regulated in more detail.

To study this, my research team and I will use tools developed in the HIV-1 vaccine field, including HIV-1 human antibody knock-in mice expressing fate-mapping genes that enable us to follow specific B cells during an ongoing immune response, after immunization with physiologically relevant HIV-1 protein antigens.

The proposal is divided into three aims over a period of 5-years.

Importantly, I expect this research to pave the way for the development of tailored vaccines that can induce more effective B cell responses of selected characteristics, needed to prevent infections by pathogens such as HIV-1, HCV, influenza virus, and other potential emerging infectious agents.