to many other vaccines similar for all age groups, including the very old. In contrast to the live-attenuated vaccine, this vaccine can also be used in immunocompromised persons, which are also at a very high risk of developing herpes zoster. Prevention of herpes zoster is of particular importance as postherpetic neuralgia, a frequent complication leading to long-term severe, hardly treatable neuropathic pain, dramatically impacts the quality of life of affected patients and frequently leads to loss of independence.
In addition, vaccines which are administered to adults of all age groups, e.g. against tetanus and diphtheria, also need to be considered in the context of aging. Tetanus- and even more so diphtheria-specific antibody concentrations decline with age, and regular vaccinations throughout adulthood are important to ensure protection also in older age. The levels of vaccination coverage and protective antibody levels vary greatly between different countries, e.g. within Europe. As many older adults are still healthy and very active, travelling to exotic destinations has become more popular among the older population. Adequate medical preparation and advice is crucial for these travelers. Besides management of underlying chronic conditions, administration of vaccines relevant for the destination and travel style is essential. In addition to classical travel vaccines, also “routine” vaccines for this age groups need to be reviewed and completed, if necessary. It has to be considered that older travelers might not respond adequately to neo-antigens and that immune responses are frequently developing slower in older adults.
There are still many pathogens which cause significant morbidity and mortality in the older population but for which vaccines are currently not available. Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections in infants, immunocompromised patients, and older adults, and vaccine development for this pathogen has been ongoing for decades. Several recent vaccine candidates have been shown to be safe and immunogenic but failed to confer protection against disease in clinical trials enrolling older adults. Recent advances in the structural biology of RSV proteins and a better understanding regarding the immune responses needed for protection might provide opportunities for the development of novel vaccine candidates. Nosocomial infections are frequent in the older population, and many of the bacterial nosocomial pathogens show increasing rates of antibiotic resistance. Vaccines against these pathogens are highly desirable, and important progress has been made in vaccine development, e.g. against Clostridium difficile and Staphylococcus aureus. There is still a plethora of microorganisms (bacterial, viral, and fungal), which are particularly pathogenic for older adults, and preclinical as we well as clinical vaccine development is ongoing for many of them. For several decades, vaccine development has been driven by the need to prevent infectious diseases in childhood. Awareness that vaccines developed for children might not be optimal for adults, and particularly for the older population has only arisen in the recent past. Novel vaccine, adjuvant, and administration strategies should also be tested in older adults. Approaches which specifically target the aged immune system and are able to overcome its limitations have great potential to provide protection from various pathogens. Scientific progress in understanding the details of immunosenescence is the basis for the development of such strategies. However, in order to exploit their full protective potential, it is essential to improve vaccine uptake throughout adulthood and particularly in the older population. Information and education of stakeholders, healthcare professionals, and the general public are important in order to increase awareness of vaccines and to overcome vaccine hesitancy. In addition, easy access – logistical and financial – to vaccines and vaccination for everyone needs to be ensured to reach vaccine uptake goals.
Birgit Weinberger, Innsbruck
Immunosenescence and Other Risk Factors Affecting Vaccination Success in Old Age
Weinberger B (ed): Vaccines for Older Adults: Current Practices and Future Opportunities. Interdiscip Top Gerontol Geriatr. Basel, Karger, 2020, vol 43, pp 1–17 (DOI:10.1159/000504480)
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How Inflammation Blunts Innate Immunity in Aging
Emily L. Goldberga Albert C. Shawb Ruth R. Montgomeryb
aDepartment of Comparative Medicine, Yale University School of Medicine, New Haven, CT, USA; bDepartment of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
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Abstract
The collective loss of immune protection during aging leads to poor vaccine responses and an increased severity of infection for the elderly. Here, we review our current understanding of effects of aging on the cellular and molecular dysregulation of innate immune cells as well as the relevant tissue milieu which influences their functions. The innate immune system is composed of multiple cell types which provide distinct and essential roles in tissue surveillance and antigen presentation as well as early responses to infection or injury. Functional defects that arise during aging lead to a reduced dynamic range of responsiveness, altered cytokine dynamics, and impaired tissue repair. Heightened inflammation influences both the dysregulation of innate immune responses as well as surrounding tissue microenvironments which have a critical role in development of a functional immune response. In particular, age-related physical and inflammatory changes in the skin, lung, lymph nodes, and adipose tissue reflect disrupted architecture and spatial organization contributing to diminished immune responsiveness. Underlying mechanisms include altered transcriptional programming and dysregulation of critical innate immune signaling cascades. Further, we identify signaling functions of bioactive lipid mediators which address chronic inflammation and may contribute to the resolution of inflammation to improve innate immunity during aging.
© 2020 S. Karger AG, Basel
Inflammation and Aging
Aging is the single greatest risk factor for developing chronic disease. Compared to younger adults, the elderly are at increased risk of infection and experience greater morbidity and mortality upon infection [1]. Similarly, the elderly also have poor vaccine responses, making them more susceptible to vaccine-preventable disease such as influenza or varicella zoster (causative agent in chickenpox and shingles) viruses, even when they have been vaccinated [2]. Central to this susceptibility is the functional deterioration of systemic immunity, or “immune senescence.” This term encompasses the collective loss of immune protection during aging and includes atrophy of the thymus leading to decreased naïve T cell output, an increased proportion of experienced lymphocytes contributing to adaptive immune memory but limiting responses to novel targets, an increased proportion of myeloid cells released from the bone marrow, and impaired functions of multiple existing immune cell types. Immune senescence is also characterized by functional dysregulation in immune cells at the cellular and molecular levels, ultimately leading to increased infection susceptibility and poor vaccination responses in the elderly as discussed in detail throughout this chapter.
Underlying many deficiencies in immunity is a chronic proinflammatory state. Many age-related diseases are driven by and promote increased inflammation, and elevated circulating inflammatory markers such as CRP, TNFα, and IL-6 correlate with age-related conditions including atherosclerosis [3] and frailty [4]. Importantly, even clinically healthy elderly individuals exhibit elevated inflammatory cytokines in serum [5]. While the precise source and cause of inflammation during aging is still unknown, this so-called “inflammaging” state contributes to the onset of multiple comorbidities in the elderly, including but not limited to Alzheimer’s disease, cardiovascular disease, muscle wasting, and immune senescence [