T-Cell Immunity to Influenza in Older Adults: A Pathophysiological Framework for Development of More Effective Vaccines

One of the most profound public health consequences of immune senescence is reflected in an increased susceptibility to influenza and other acute respiratory illnesses, as well as a loss of influenza vaccine effectiveness in older people. Common medical conditions and mental and psychosocial health issues as well as degree of frailty and functional dependence accelerate changes associated with immune senescence. All contribute to the increased risk for complications of influenza infection, including pneumonias, heart diseases, and strokes that lead to hospitalization, disability, and death in the over 65 population. Changes in mucosal barrier mechanisms and both innate and adaptive immune functions converge in the reduced response to influenza infection, and lead to a loss of antibody-mediated protection against influenza with age. The interactions of immune senescence and reduced adaptive immune responses, persistent cytomegalovirus infection, inflammaging (chronic elevation of inflammatory cytokines), and dysregulated cytokine production, pose major challenges to the development of vaccines designed to improve T-cell-mediated immunity. In older adults, the goal of vaccination is more realistically targeted to providing clinical protection against disease rather than to inducing sterilizing immunity to infection. Standard assays of antibody titers correlate with protection against influenza illness but do not detect important changes in cellular immune mechanisms that correlate with vaccine-mediated protection against influenza in older people. This article will discuss: (i) the burden of influenza in older adults and how this relates to changes in T-cell function, (ii) age-related changes in different T-cell subsets and immunologic targets for improved influenza vaccine efficacy in older, and (iii) the development of correlates of clinical protection against influenza disease to expedite the process of new vaccine development for the 65 and older population. Ultimately, these efforts will address the public health need for improved protection against influenza in older adults and vaccine preventable disability

The role of inflammation in age-related disease.

The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation inAge-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified

Royal society of Canada COVID-19 report: Enhancing COVID-19 vaccine acceptance in Canada

COVID-19 vaccine acceptance exists on a continuum from a minority who strongly oppose vaccination, to the moveable middle heterogeneous group with varying uncertainty levels about acceptance or hesitancy, to the majority who state willingness to be vaccinated. Intention for vaccine acceptance varies over time. COVID-19 vaccination decisions are influenced by many factors including knowledge, attitudes, and beliefs; social networks; communication environment; COVID-19 community rate; cultural and religious influences; ease of access; and the organization of health and community services and policies. Reflecting vaccine acceptance complexity, the Royal Society of Canada Working Group on COVID-19 Vaccine Acceptance developed a framework with four major factor domains that influence vaccine acceptance (people, communities, health care workers; immunization knowledge; health care and public health systems including federal/provincial/territorial/indigenous factors) - each influencing the others and all influenced by education, infection control, extent of collaborations, and communications about COVID-19 immunization. The Working Group then developed 37 interrelated recommendations to support COVID vaccine acceptance nested under four categories of responsibility: 1. People and Communities, 2. Health Care Workers, 3. Health Care System and Local Public Health Units, and 4. Federal/Provincial/Territorial/Indigenous. To optimize outcomes, all must be engaged to ensure co-development and broad ownership

IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans

An age-related decline in cytolytic activity has been described in CD8+ T cells and we have previously shown that the poor CD8+ effector T cell responses to influenza A/H3N2 challenge result from a decline in the proportion and function of these cytolytic T lymphocytes (CTL). Here, we describe that addition of exogenous cytokines to influenza-stimulated PBMC from both aged mice and humans, enhances the generation of influenza specific CD8 CTL by increasing their proliferation and survival. Our data show that the addition of IL-2 and IL-6 to splenocytes from mice previously infected with influenza virus restores the aged CD8+ T cell response to that observed in young mice. In humans, IL-2 plus IL-6 also reduces the proportion of apoptotic effector CD8+ T cells to levels resembling those of younger adults. In HLA-A2+ donors, MHC Class I tetramer staining showed that adding both exogenous IL-2 and IL-6 resulted in greater differentiation into influenza-specific effector CD8+ T cells. Since this effect of IL-2/IL-6 supplementation can be reproduced with the addition of Toll-like receptor agonists, it may be possible to exploit this mechanism and design new vaccines to improve the CD8 T cell response to influenza vaccination in older adults

COVID-19, frailty and long-term care: Implications for policy and practice

Older adults have been disproportionately affected by the COVID-19 pandemic, with many outbreaks occurring in Long Term Care Facilities (LTCFs). We discuss this vulnerability among LTCF residents using an ecological framework, on levels spanning from the individual to families and caregivers, institutions, health services and systems, communities, and contextual government policies. Challenges abound for fully understanding the burden of COVID-19 in LTCF, including differences in nomenclature, data collection systems, cultural differences, varied social welfare models, and (often) under-resourcing of the LTC sector. Registration of cases and deaths may be limited by testing capacity and policy, record-keeping and reporting procedures. Hospitalization and death rates may be inaccurate depending on atypical presentations and whether or not residents' goals of care include escalation of care and transfer to hospital. Given the important contribution of frailty, use of the Clinical Frailty Scale (CFS) is discussed as a readily implementable measure, as are lessons learned from the study of frailty in relation to influenza. Biomarkers hold emerging promise in helping to predict disease severity and address the puzzle of why some frail LTCF residents are resilient to COVID-19, either remaining test-negative despite exposure or having asymptomatic infection, while others experience the full range of illness severity including critical illness and death. Strong and coordinated surveillance and research focused on LTCFs and their frail residents is required. These efforts should include widespread assessment of frailty using feasible and readily implementable tools such as the CFS, and rigorous reporting of morbidity and mortality in LTCFs

Quality-of-Life Impact of an Investigational Subunit-Adjuvanted Herpes Zoster Vaccine in Adults ≥50 Years of Age

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Efficacy, Immunogenicity and Safety of an Investigational Subunit Adjuvanted Herpes Zoster Vaccine in Adults Aged 60 Years and Older: Results From the ZOE-50 and ZOE-70 Efficacy Studies

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Vaccination programs for older adults in an era of demographic change

Objectives Populations are aging worldwide. This paper summarizes some of the challenges and opportunities due to the increasing burden of infectious diseases in an aging population. Results Older adults typically suffer elevated morbidity from infectious disease, leading to increased demand for healthcare resources and higher healthcare costs. Preventive medicine, including vaccination can potentially play a major role in preserving the health and independence of older adults. However, this potential of widespread vaccination is rarely realized. Here, we give a brief overview of the problem, discuss concrete obstacles and the potential for expanded vaccination programs to promote healthy aging. Conclusion The increasing healthcare burden of infectious diseases expected in aging populations could, to a large extent, be reduced by achieving higher vaccination coverage among older adults. Vaccination can thus contribute to healthy aging, alongside healthy diet and physical exercise. The available evidence indicates that dedicated programs can achieve substantial improvements in vaccination coverage among older adults, but more research is required to assess the generalizability of the results achieved by specific interventions (see Additional file 1)

As atitudes dos professores do 1º, 2º e 3º ciclos do ensino básico face à inclusão de alunos com a síndrome de Asperger no ensino regular

A incessante procura de conhecer e perceber o Ser Humano, leva os cientistas a descobrir os processos psicológicos do Homem. A Síndrome de Asperger é uma categoria recente da investigação científica e ainda existe pouca informação relativamente a este assunto. As crianças/jovens com a Síndrome de Asperger não apresentam qualquer atraso no desenvolvimento da fala ou cognitivo porém é importante que esta receba uma educação especializada o mais cedo possível. (Teixeira, s.d.) Actualmente, uma das metas da escola, é levar aos alunos a aprender as normas da cultura onde encontram-se inseridos (solidariedade, respeito, cooperação…) mas também deve dar condições para que construam e interiorizem tais valores. O direito a uma igualdade de oportunidades exige da escola as melhores condições possíveis e profissionais cada vez mais qualificados para a formação de alunos que necessitam de uma educação especial. Assim é necessário conhecer as estratégias de ensino individual e transmitir aos alunos certas ferramentas para que estes recebam um ensino adequado à sua patologia. Os professores têm um papel importante neste processo, pois são os responsáveis na formação do indivíduo, são estes que fornecem-lhe as ferramentas/conhecimentos necessários para o convívio em sociedade. (Guimarães, s.d.) O presente estudo propõe-se descrever as atitudes dos professores do 1º, 2º e 3º ciclos do ensino básico face à inclusão de alunos com a Síndrome de Asperger no ensino regular. O objectivo do trabalho consiste em saber quais as variáveis que influenciam as atitudes dos professores face à inclusão de alunos com a Síndrome de Asperger, tentando relacionar o nível de ensino (1º, 2º e 3º ciclos) com as atitudes mais ou menos favoráveis apresentadas pelos docentes

Influenza-Specific T Cells from Older People Are Enriched in the Late Effector Subset and Their Presence Inversely Correlates with Vaccine Response

T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64) and younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34) ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1+CD57+ influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8+KLRG1+CD57+ population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age