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Background While both cellular and humoral immunity are important in immunologic protection against influenza, how the influenza-specific CD4 T cell response is established in response to early vaccination remains inadequately understood. In this study, we sought to understand how the CD4 T cell response to inactivated influenza vaccine (IIV) is established and develops throughout early childhood. Methods Influenza-specific CD4 T cell responses were quantified following IIV over 2 influenza seasons in 47 vaccinated children between 6 months and 8 years of age who had no documented history of natural influenza infection during the study. Peripheral blood mononuclear cells were stimulated with peptide pools encompassing the translated regions of the pH1, H3, HAB, and NP proteins, and CD4 T cell responses were assessed via multiparameter flow cytometry. Results There was boosting of H3- and HAB-specific CD4 T cells but not cells specific for the pH1 HA protein post-vaccination. A positive correlation between age and the magnitude of the influenza-specific CD4 T cell response was seen, with an overall greater magnitude of IFNγ-producing cells in subjects ≥3 years of age. Changes in CD4 T cell functionality were also noted in older compared to younger children, with increases in CD4 T cells producing IFNγ and TNF or IL-2 as well as IFNγ alone. Conclusions Inactivated influenza vaccine elicits a CD4 T cell response to H3 and HAB, with increases in the magnitude of the CD4 T cell response and changes in cellular functionality throughout childhood. This suggests that repeated influenza vaccination contributes to the development of anti-influenza CD4 T cell memory in children. [ABSTRACT FROM AUTHOR]

Background: Early childhood influenza infections imprint influenza-specific immune memory, with most studies evaluating antibody specificity. In this study, we examined how infection versus inactivated influenza vaccination (IIV) establish pediatric CD4 T-cell mediated immunity to influenza and whether this poises the immune system to respond differently to IIV the following year.Methods: We tracked influenza-specific CD4 T-cell responses in 16 H3N2 infected and 28 IIV immunized children following both initial exposure and after cohorts were revaccinated with IIV the following fall. PBMCs were stimulated with peptide pools encompassing the translated regions of the H3 HA and NP proteins and were then stained to assess CD4 T-cell specificity and function.Results: Compared to IIV, infection primed a greater magnitude CD4 T-cell response specific for the infecting HA and NP proteins, with more robust NP-specific immunity persisting through year 2. Post infection, CD4 T cells preferentially produced combinations of cytokines that included interferon-γ. Interestingly, age-specific patterns in CD4 T-cell reactivity demonstrated the impact of multiple influenza exposures over time.Conclusions: These data indicate that infection and vaccination differentially prime influenza-specific CD4 T-cell responses in early childhood, with these differences contributing to the lasting immunologic imprinting established following early influenza infection.Clinical Trials Registration: NCT02559505. [ABSTRACT FROM AUTHOR]

This article uses data from recent interviews with chief police officers in England and Wales to assess the connections between how chief police officers are overseen and given political direction and police legitimacy. The research found that governance changes started in 2011, particularly the election of police and crime commissioners, led to chief officers feeling more anxious, and the reforms reduced their operational independence. This may result in chief officers being less able to resist demands to encroach on civil liberties, prioritize the needs of the powerful over the marginalized, or to challenge policies that are likely to be ineffective or which neglect many peoples' priorities. This endangers effective police leadership and legitimacy. Suggestions are made for consideration by policy makers, practitioners, and researchers to enhance police governance, leadership, and legitimacy. It is contended that the findings have implications for governance, leadership, and legitimacy in other countries and sectors. [ABSTRACT FROM AUTHOR]

Despite the benefits of yearly influenza vaccination, accumulating evidence suggests that diminished vaccine efficacy may be related to repeated vaccination. Although studied at the level of B-cell responses, CD4 T-cell responses have not yet been examined. In this study, we analyze CD4 T-cell responses to influenza vaccination in subjects who differ in their vaccine history. We find a striking disparity in their responses, with previously vaccinated subjects exhibiting significantly blunted CD4 T-cell responses and diminished antibody responses. These results suggest that limiting CD4 T-cell help mteaserrlie the diminished or altered antibody responses in repeatedly vaccinated subjects. [ABSTRACT FROM AUTHOR]

Live attenuated influenza vaccine (LAIV), or FluMist, was approved for use in the United States in 2003. This vaccine, administered intranasally, offers the advantage of stimulating immunity at the site of infection in the upper respiratory tract and, by mimicking natural infection, has the potential to elicit a multifaceted immune response. However, the development of immunity following LAIV administration requires viral replication, causing vaccine effectiveness to be impacted by both the replicative fitness of the attenuated viruses being administered and the degree of the host's preexisting immunity. In this review, we discuss the current state of knowledge regarding the mechanisms of protection elicited by LAIV in children, contrast this with immune protection that develops upon vaccination with inactivated influenza vaccines, and briefly discuss both the potential advantages as well as challenges offered by this vaccination platform. [ABSTRACT FROM AUTHOR]