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Vaccines for Older Adults: Current Practices and Future Opportunities


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Future of Vaccines for the Older Population

       Vaccination against Respiratory Syncytial Virus

      Green, C.A. (Oxford/Birmingham); Drysdale, S.B. (Oxford/London); Pollard, A.J. (Oxford); Sande, C.J. (Oxford/Kilifi)

       Vaccination Against Nosocomial Infections in Elderly Adults

      Anderson, A.S.; Scully, I.L.; Pride, M.W.; Jansen, K.U. (Pearl River, NY)

       Novel Technologies to Improve Vaccines for Older Adults

      Laupèze, B.; van der Most, R. (Wavre); Del Giudice, G. (Siena)

       Strategies to Improve Vaccine Uptake throughout Adulthood

      Ecarnot, F. (Besançon); Maggi, S. (Padua); Michel, J.-P. (Geneva)

       Author Index

       Subject Index

      Weinberger B (ed): Vaccines for Older Adults: Current Practices and Future Opportunities. Interdiscip Top Gerontol Geriatr. Basel, Karger, 2020, vol 43, pp VI–IX (DOI:10.1159/000504488)

      Demographic changes lead to an increase in the number and percentage of older persons worldwide. It is estimated that by 2080 the median age of the population in Europe will increase by 4.2 years, and the proportion of older persons (>65 years) will increase from 19.2 to 29.1% during this time. The proportion of the very old (>80 years) will increase even more, from 5.4 to 12.4%. In view of these developments, it is of utmost importance to the individual person as well as to society as a whole to promote healthy aging and ensure quality of life for the older population.

      Many infectious diseases show increased incidence and severity with age. In addition to the acute event of infection, which is often associated with high morbidity and mortality in older age groups, there can be severe additional, often long-term consequences. Exacerbations of underlying chronic diseases during or shortly after infections are frequent, and many older patients will not recover fully after serious infections. In the worst-case scenario, this leads to a loss of independence, which might necessitate admission to long-term care. Vaccines are the most efficient strategy to prevent infectious diseases, and the tremendous success of childhood vaccination programs in reducing the burden of many infectious diseases worldwide is undisputed. Prevention of infections affecting the older population by vaccination is an important measure to achieve the overall goal of promoting health in this age group.

      This book summarizes age-related changes of the immune system and their impact on immune responses to vaccination, as well as other factors influencing vaccine-induced immune responses in old age. It gives an overview of vaccines which are currently available for older adults and of novel technologies and targets which hopefully will lead to more and improved vaccines for this vulnerable population.

      The immune system is a complex network of different cell types and soluble factors, with intricate interactions not only amongst its components but also with the rest of the body. The innate immune system consists of several cell types with distinct roles in early immune responses and antigen presentation. Alterations in receptor expression, signaling, transcriptional programming and cytokine production and responsiveness are contributing to age-related functional defects in neutrophils, monocytes/macrophages and dendritic cells. Natural killer cells, which recognize and eliminate infected and tumor cells, show age-related changes in their phenotype and subset composition as well as their functions, which includes cytotoxicity and cytokine production. The aged adaptive immune system is characterized by a diminished repertoire and diversity. Age-associated changes in hematopoiesis and involution of the thymus lead to decreased output of newly generated naïve T cells. At the same time, antigen-experienced T cells, and particularly highly differentiated effector T cells accumulate. Signaling defects, limited proliferative capacity of exhausted or senescent-like T cells, and alterations in cytokine production contribute to decreased T cell function in old age. The output of naïve B cells is also decreased, and the composition of the B cell compartment changes with age. Intrinsic defects of B cells as well as age-related changes of other cell types interacting with B cells, particularly T helper cells, contribute to decreased production of specific antibodies upon antigenic challenge. At the same time, increased frequencies of autoreactive antibodies can be observed in old age. Metabolic changes have been described for many immune cell types and their relevance for immunological functions is more and more recognized in the field. A chronic subclinical inflammatory status has been observed in older adults, which can be attributed to altered cytokine production by innate and adaptive immune cells, as well as other cell types, such as adipocytes, fibroblasts, and many others. In addition to its impact on the regulation of immune responses, this inflammatory background has been described to contribute to many age-associated diseases, such as e.g. atherosclerosis and neurodegeneration.

      Age-related changes of the immune system have a direct impact on vaccine-induced immune responses. Innate immune cells recognize vaccine components (antigens and adjuvants) at the site of injection and elicit a local inflammatory response. Antigens are taken up by phagocytes and are presented to T cells. Adaptive immune responses in the lymph nodes involve myeloid cells, as well as T cells and B cells. In most cases, antibody concentrations are measured to determine immunogenicity of a vaccine. It has to be taken into account that T cell help is crucial for optimal antibody production and that T cells also play an important role in conferring protection from many infectious diseases. In addition, other factors such as underlying chronic diseases, which are highly prevalent in the older population, and frailty negatively influence vaccine-induced immune responses. The influence of adipose tissue on immune responses needs be considered, and research in this area has expanded over the last years, particularly in view of an increasing prevalence of obesity.

      Many countries have specific vaccine recommendations in place for older adults. Vaccination against influenza and pneumococcal disease is advocated throughout Europe. An increasing number of countries also include vaccination against herpes zoster in their recommendations. Antibody responses following influenza and pneumococcal vaccination are generally lower in older compared to younger adults. Various strategies have been employed to improve immunogenicity of influenza vaccines including higher antigen content, alternative administration routes and adjuvants, generally leading to slightly higher antibody responses. It has to be taken into account that antibodies might not be the only mechanism conferring protection. Over the last year vaccine-induced T cell responses have been studied in more detail. However, large-scale clinical trials still rely mainly on antibody-related parameters as measurement of T cell responses is technically more complex and therefore difficult for large sample numbers. Protection of the older population against pneumococcal disease remains a challenge. Vaccination of children with conjugated pneumococcal vaccines provides some protection of the older population via herd immunity effects, but vaccination of older adults offers more direct protection. A 23-valent polysaccharide vaccine and a 13-valent conjugate vaccine are currently available for the older population but have limitations, such as relatively short-lived protection and the restricted serotype coverage. Several countries recommend sequential vaccination with the conjugate and then the polysaccharide vaccine in order to combine benefits from both vaccine types. For both influenza and Streptococcus pneumoniae, efforts to develop “universal” vaccines containing conserved antigens, which would cover many or all strains or serotypes, respectively, are ongoing. This strategy could overcome current limitations, such as the need for annual re-vaccination against influenza and serotype replacement for S. pneumoniae. A first live-attenuated vaccine against herpes zoster was recently replaced by a recombinant vaccine containing the viral glycoprotein gE and the adjuvant AS01B. The efficacy of the recombinant vaccine