Mass vaccination campaigns started quickly in many countries, but due to limited vaccine supply during the first months, prioritization of who was to be vaccinated first was necessary. countries and clinical development for more vaccine candidates is ongoing, but a complete overview of COVID-19 vaccine development is beyond the scope of this article. strong class=”kwd-title” Keywords: SARS-CoV-2, COVID-19, vaccine, vaccination, elderly, aging 1. Introduction The immune system undergoes characteristic changes with age, which lead to dysregulation and functional deficits of many immune mechanisms. Functional changes of innate immune cells impact the first line of immunological defense as well as the induction of adaptive immune responses. In the context of vaccination, innate immune cells at the site of injection are crucial for successful immune responses. Neutrophils contribute to a proinflammatory environment at the site of infection or vaccine delivery and play an important role in the recruitment and activation of other innate immune cells, e.g., monocytes/macrophages and dendritic cells (DC). Neutrophils from older persons have been shown to display reduced chemotaxis, altered signal transduction following antigen recognition and aberrant cytokine production [1]. Similar defects can be observed in monocytes/macrophages and DCs. In addition, their capacity to process and present antigen to T cells is decreased e.g., due to alterations in the upregulation of MHC-proteins and other stimulatory molecules after antigen contact [2]. Alterations in hematopoiesis and thymic involution lead to substantial changes in the composition of the T cell BRL 52537 HCl compartment with age. The output of newly generated na?ve T cells decreases whereas antigen-experienced, highly-differentiated T cells, which have been repeatedly stimulated by antigen, accumulate. These cells show a reduced response to antigenic stimulation, produce preferentially proinflammatory cytokines, and are restricted in their diversity [3,4,5]. The composition of the B cell pool also changes with age, and an increase of B cells BRL 52537 HCl with lower affinity or autoreactivity can be observed. Lower numbers of antibody-producing plasma cells can be observed after vaccination and intrinsic defects of B cells, such as reduced isotype switch and affinity maturation, further contribute to lower antibody responses [6]. Interactions of B cells with follicular T helper cells in germinal centers are crucial for antibody responses. Age-related deficits of this cell type need to be taken into account, and have recently been summarized elsewhere [7]. An extensive review of immunosenescence and other factors influencing immune responses to vaccination is beyond the scope of this article, but can be found elsewhere [8,9,10,11,12]. As a consequence of immunosenescence, incidence, morbidity, and mortality of many infectious diseases are increased in older adults [13]. Additional risk factors for infections include chronic comorbidities, such as cardiovascular disease, kidney disease, diabetes or malignancies, Mouse monoclonal to CD14.4AW4 reacts with CD14, a 53-55 kDa molecule. CD14 is a human high affinity cell-surface receptor for complexes of lipopolysaccharide (LPS-endotoxin) and serum LPS-binding protein (LPB). CD14 antigen has a strong presence on the surface of monocytes/macrophages, is weakly expressed on granulocytes, but not expressed by myeloid progenitor cells. CD14 functions as a receptor for endotoxin; when the monocytes become activated they release cytokines such as TNF, and up-regulate cell surface molecules including adhesion molecules.This clone is cross reactive with non-human primate which are frequent in the older population, and obesity, as well as immunosuppressive treatments, e.g., in the context of organ transplantation, chemotherapy or immunomodulatory treatment of autoimmune disease. These phenomena have been observed and studied (e.g., for influenza, pneumococcal disease, and herpes zoster) for a long time [14,15,16]. At the same time, immunogenicity and clinical efficacy/effectiveness are lower in older adults for many, but not all vaccines [17,18,19]. In the current SARS-CoV-2 pandemic very heterogeneous medical presentations of COVID-19 disease BRL 52537 HCl have been observed, ranging from asymptomatic to severe and fatal disease. Recognition of risk factors is vital for mitigation strategies, and a plethora of studies tackled these questions early in the pandemic. They found that the risk for severe disease and death from COVID-19 is definitely highest in older adults, individuals with underlying co-morbidities, and obese individuals [20,21,22,23]. A systematic review summarizing 76 studies and a total of more than 153,000 individuals confirmed these findings and reported age above 75 years (OR: 2.65, 95% CI: 1.81C3.90), male sex (OR: 2.05, 95% CI: 1.39C3.04) and severe obesity (OR: 2.57, 95% CI: 1.31C5.05) as the greatest risk factors for severe disease. When considering mortality as the outcome, the danger associated with age 75 is elevated further (OR: 5.57, 95% CI: 3.10C10.00) [20]. Another study compiled data from several countries and determined that COVID-19 hospitalization rates increase exponentially with age and double every 16 years.