However, we found an inverse correlation in all three influenza virus types between the serological levels of a given influenza virus strain present on the day of vaccination and the magnitude of the subsequent vaccine-induced plasmablast response (Fig

However, we found an inverse correlation in all three influenza virus types between the serological levels of a given influenza virus strain present on the day of vaccination and the magnitude of the subsequent vaccine-induced plasmablast response (Fig. broader immunological context of viral antigen exposure, the B cell response to variant influenza computer virus strains is not dictated by the composition of the memory B cell precursor pool. The outcome is usually instead a diversified B cell response. IMPORTANCE Vaccine strategies are being designed to boost broadly reactive B cells present in the memory repertoire to provide universal protection to the influenza computer virus. It is important to understand how past exposure to influenza computer virus strains affects the response to subsequent immunizations. The viral epitopes targeted by B cells responding to the vaccine may be a direct reflection of the B cell memory specificities abundant in the preexisting immune repertoire, or other factors may influence the vaccine response. Here, we demonstrate that high preexisting serological antibody levels to a given influenza computer virus strain correlate with low production of antibody-secreting cells and memory B cells recognizing that strain upon revaccination. In contrast, introduction of antigenically novel strains generates a strong B cell response. Thus, both the preexisting memory B cell repertoire and serological antibody levels must be taken into consideration in predicting the quality of the B cell response to new prime-boost vaccine strategies. INTRODUCTION A primary immune response induced upon first exposure to a given antigen is Triethyl citrate characterized by a wave of low-affinity IgM B cells activated from the naive B cell pool with few to no mutations in their immunoglobulin (Ig) genes. This is followed by isotype-switched, higher-affinity B cells generated from germinal center reactions with greater numbers of genetic mutations (1, 2). Subsequent exposures, or secondary responses, are largely driven by activated and differentiated memory B cells and thus dominated by mutated, isotype-switched, medium- to high-affinity B cells (1, 3, 4). While this profound Triethyl citrate difference between the primary and secondary immune responses is relatively straightforward upon repeated exposure to the same antigen, it is less clear how the immune system responds to challenge with a varying antigen such as the influenza computer virus. Due to the evolving nature of the influenza computer virus, individuals are repeatedly uncovered over their lifetimes to viral strains made up of both novel and immune-experienced epitopes (5). In keeping with the very definition of immune memory, the memory response to conserved epitopes encountered before should dominate the response to novel epitopes introduced by mutations in divergent influenza computer virus strains. If the magnitude of the immune response is usually driven solely by the memory B cell repertoire, then one would expect these repeated exposures to influenza computer virus to progressively focus the B cell repertoire toward viral strain epitopes encountered multiple occasions. Two computer virus Rabbit Polyclonal to TTF2 types, influenza A and B viruses, circulate in the human population. Influenza A computer virus is usually further subdivided into different subtypes based on characterization of the two major envelope proteins, hemagglutinin (HA) and neuraminidase (NA). H1N1 and H3N2 are the two predominant influenza A computer virus subtypes currently circulating in the human population. Influenza B computer virus can be divided into two coevolved lineages, with one or the other being more dominant from 12 months to 12 months. The annual inactivated influenza trivalent vaccine (TIV) contains influenza A H1N1 and H3N2 and influenza B computer virus strains projected to be in circulation. Produced every year, the vaccine may contain the same strain(s) as in the previous year’s vaccine or may include a Triethyl citrate more divergent strain in the case of antigenic drift away from previously circulating strains. This allows us to inquire if from 12 months to 12 months the vaccine-induced B cell response is usually favored toward repeated or divergent strains. If the extent of the immune response is determined predominantly by the prevaccination levels of memory B cells specific to a given strain, then the immune response should be dominated by B cells recognizing a repeated strain at the expense of more variant strains. However, early influenza vaccine studies showed an inverse correlation between preexisting serum antibody (Ab) levels to a given influenza Triethyl citrate computer virus strain and subsequent serological Ab levels upon vaccination with that.