Delineating Humoral and Cellular Responses to Influenza Vaccination in Young Children

The facts that young children are considered as a high-risk group for influenza attack and serious complications, that young children generally have poor immunogenicity to inactivated influenza vaccine, and that a high HI antibody titer might be required for protection in children, illustrate the importance of comprehensively exploring the humoral and cellular immune response to influenza virus in young children. Neutralizing antibodies induced by previous natural infection or vaccination, play a critical part in antibody-mediated immunity against influenza virus. The maintenance of antibody immunity is primarily mediated through isotype-switched memory B cells, alongside plasma cells. In adults, the preliminary result showed that pre-existing memory B cells represented the origin of a robust acute-phase plasma cell response detected in the peripheral blood upon flu vaccination or infection. These plasma cells were highly somatic mutated on Ig variable region and secrete high-affinity flu-specific antibodies. Anti-influenza monoclonal antibodies retrieved from acute-phase plasma cell response, which represent the flu-specific B cell repertoire upon antigen exposure, were genetically and functionally diverse. In young children, we hypothesize the lack of immunological experience with influenza and the immunogenic immaturity might lead to the low pre-existing antibody level, might affect the development of antibody, B and T cell response, and might impair the quality of flu-specific B cell repertoire to influenza virus. In this project, we will carry out a prospective, longitudinal and comprehensive study to investigate humoral and cellular immune responses in young children receiving consecutive immunizations of 2012, 2013 and 2014 inactivated trivalent influenza vaccines. The longitudinal samples will be utilized to study the kinetics and magnitude of flu-specific memory B, plasma and T cell in the primary and secondary response. The immune response will be correlated with serum polyclonal antibody level and also be compared among different age groups. Importantly, a flow -cytometry based assay will be setup to examine flu-specific B cells as an independent parameter of antigen-specific humoral immunity. Flu-specific B cells will be further collected at a single cell level for clonality analysis. The immunoglobulin variable region gene from the single B cell will be sequenced and the sequence data will provide important information on the clonal expansion of flu-specific B cells, the gene usage and the level and somatic hypermutation of flu-specific B cell repertoire during the course of vaccination. The function of monoclonal antibodies will provide a powerful tool to study the quality of flu-specific B cell repertoire as well. This project will generate a good understanding of the antibody, B and T cell response to influenza virus in young children at the serology, cellular and sequence level, which will also be pivotal in future generation of vaccine development and validation.

Project ID:PC10108-0668
External Project ID:NSC101-2314-B182-014-MY3