Indeed, after the United Kingdom commenced LAIV vaccination of children, signs of herd immunity have been observed in areas with widespread vaccination, such as reduced hospital admission of children . increase in cross-reactive tonsillar CD8+ T cells recognizing conserved epitopes from a broad range of seasonal and pandemic viruses occurred at day 14. Tonsillar T cells showed significant cytokine responses (Th1, Th2, and granulocyte-macrophage colony-stimulating factor). Conclusions Our findings support the use of LAIV in children to elicit broadly cross-reactive T cells, which are not induced by traditional inactivated influenza vaccines and may provide protection to novel virus strains. .05 was considered significant. RESULTS Early Hemagglutination Inhibition Antibody Responses After Live-Attenuated Influenza Vaccine The influenza-specific HI responses were measured after LAIV. The majority of subjects (59%) had prevaccination HI titers 40 to H1N1, and no increase in (-)-Catechin gallate antibodies was observed after vaccination, except for 1 subject (Figure 2). H3N2-specific HI titers 40 were observed in 49% of children prevaccination, and titers increased from day 14 with all subjects having titers 40 at day 56. Most children (89%) had no prevaccination HI antibodies to influenza B, but antibodies increased at day Rabbit Polyclonal to MOBKL2A/B 14. By 56 days postvaccination, 84% of children had titers 40. The nonvaccinated controls had similar antibody titers to the prevaccination titers of the vaccinees, supporting their use as relevant controls for analysis of tonsillar T cells. Open in a separate window Figure 2. Serum hemagglutination inhibition (HI) antibody response after live-attenuated influenza vaccine (LAIV). Plasma was collected pre- and postvaccination including at the time of (-)-Catechin gallate tonsillectomy from children vaccinated with LAIV. The data show the influenza A H1N1 (A), influenza A H3N2 (B), and (C) B-strain specific HI responses of each individual subject. Influenza strain-specific HI antibody was measured by HI assay, prevaccination (day 0), the day of tonsillectomy (day 3, 7, or 14), and days 28 and 56 postvaccination. Control refers to the nonvaccinated group, which had similar HI titers as the day 0 vaccinees supporting their use as controls for the tonsillar results. The horizontal lines represent the geometric mean titers 95% confidence interval. The dotted line represents an HI titer of 40 regarded as protective antibody titers. Interferon- T-Cell Responses in Tonsils and Blood Antigen-specific IFN- responses were measured in TMCs and PBMCs from LAIV-vaccinated and control subjects after stimulation with either split antigens (Figure 3) or peptides representing conserved CD4+ and CD8+ T-cell epitopes (Figure 4). Low levels of H1N1-specific IFN–secreting TMCs were detected in nonvaccinated controls, and no increase in IFN–secreting TMC response was detected (-)-Catechin gallate after vaccination. These findings were confirmed by using CD4+ and CD8+ H1N1-specific peptides (Supplementary Figure 1). In contrast, the H1N1-specific IFN- response in PBMCs was significantly enhanced from (-)-Catechin gallate day (-)-Catechin gallate 0 and 3 to 56 days postvaccination (means = 58C167 and 9C167 spot-forming units [SFU]/1 106 cells, respectively), with a peak reached at day 14 (mean 200 SFU/1 106 cells). The H3N2-specific IFN- response of TMC was higher 14 days postvaccination compared with controls (day 14 mean = 181 and control = 80 IFN- SFU/1 106 cells, respectively), although not statistically significant. Vaccination did not significantly enhance the H3N2-specific IFN- response in PBMCs. In contrast, both the tonsillar and the systemic PBMC B-strain-specific IFN- responses were significantly higher 14 days postvaccination compared with the nonvaccinated subjects (tonsillar mean = 134 and systemic mean 325 versus nonvaccinated tonsillar mean = 18 and systemic mean = 58 IFN- SFU/1 106 cells, respectively). Open in a separate window Figure 3. Strain-specific T-cell responses in tonsils and peripheral blood mononuclear cells (PBMCs) after live-attenuated influenza vaccination (LAIV). The influenza H1N1, H3N2, and B strain-specific interferon (IFN)-.