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.
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.
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).
Worldwide, populations are aging due to ever increasing life expectancy and decreasing birth rates. The United Nations estimates that 15% of the world’s population will be over the age of 60 years by 2025 and that this proportion will rise to well over 20% by 2050 . In Europe as well as Japan, the proportion of people aged 65 years or older will double from 2010 to 2060 and the proportion of people aged 65 years or older relative to the population of working age (15–64 years) is expected to double by 2060.
This demographic development is already starting to put considerable strain on public finances in countries with state-financed pensions and healthcare systems and the effects can only be expected to increase [2, 3]. Without substantial (and politically difficult) changes in policy, the tax base will diminish because of the fall in the proportion of working age (and tax-paying) adults while pension expenses will grow, both because of continued increases in life expectancy and the sheer growth in the number of people eligible for pensions. Furthermore, it is expected that healthcare expenditures will increase substantially, as individual need for healthcare services rises markedly with advancing age.
Only recently have the implications and the dimensions of the coming problems been more widely recognized, leading to various strategies being debated. These various measures are aimed at keeping older adults economically and socially active longer than has been common in prior generations on the one hand—the concept of “adding life to years”—and on the other to delay as much as possible the inevitable age-related increase in healthcare utilization—a concept designated as “healthy aging” .
The World Health Organization has recently defined the concept of healthy aging as “the process of developing and maintaining the functional ability that enables well-being in older age” . Healthy aging is obviously a laudable objective on its own to improve welfare and quality of life (QoL), but it is also specifically recognized as necessary to counter the anticipated surge in healthcare costs consequent on the demographic change underway.
Traditional stereotypes are no longer applicable to the current population of older adults, who are often healthier and more active than prior generations and the focus today is not on chronological age but on functional ability and independence . In particular, there is consensus that we need to delay the onset of “frailty”, a common clinical syndrome in older adults that carries an increased risk for poor health outcomes including disability, hospitalization and mortality [5, 6] (Fig. 1). Development of frailty is often associated with a decreased ability to respond to immune stimuli, so-called immunosenescence (see Text Box 1). Lower immune responses in older adults correlate with higher susceptibility to infectious diseases and a higher risk of hospitalization or serious outcomes than in a younger person, further complicated by the higher prevalence of comorbidities common in older adults .
For example, infections of the lower respiratory tract are now the fourth most frequent cause of death in developed countries, with approximately 75% of cases occurring in adults aged 60 years and older [8, 9]. As another example, in the United States it is estimated that 40,000–80,000 people die annually from vaccine-preventable diseases (VPDs), while hundreds of thousands more are hospitalized [1, 10]. The majority of cases and 99% of the deaths from VPDs are in older adults . Given these numbers and existing trends in disease incidence, infectious diseases represent a major barrier to healthy aging and the burden of infectious diseases in adults over age 60 years is coming to represent a significant and increasing proportion of healthcare expenditures .
Vaccination—a tool for healthy aging
Increasing vaccination coverage of older adults against VPDs can be expected to promote healthy aging. The VPDs particularly relevant for older adults currently include seasonal influenza, invasive pneumococcal diseases, pneumonia, herpes zoster (shingles), meningococcal diseases, pertussis, diphtheria, tetanus and hepatitis . Numerous studies have been carried out to assess vaccination of older adults against these VPDs in terms of avoided cases and savings in healthcare resources and costs (e.g., [10, 22,23,24]). As just one example, a Europe-wide study showed that vaccination coverage of 75% of adults over 65 against seasonal influenza could result in 1.6–2.1 million cases prevented, 25,000–37,000 influenza-related deaths avoided and savings of healthcare costs amounting to €153–219 million annually . This is probably only the tip of the iceberg as there is substantial additional morbidity associated with infectious diseases in terms of serious sequelae (see Text Box 2). Even when vaccination is not 100% effective in preventing infection with a pathogen, it may still attenuate the course and severity of a disease [25, 26].
Despite the availability of effective and well-tolerated vaccines against these diseases, many countries struggle to reach recommended coverage levels even when vaccination is supported by national programs. The reasons include lack of knowledge, poor infrastructure for adult vaccination or perceptions that the benefits of vaccination of older adults may not justify the costs (see Text Box 3).
Human aging is characterized by a chronic, low-grade inflammation, a phenomenon termed “inflammaging”, which is a highly significant risk factor for morbidity, frailty and mortality in older adults as most, if not all, age-related diseases share an inflammatory pathogenesis . This low-grade inflammation not only accelerates tissue degeneration and wasting, but also influences adaptive immune responses which are at the core of generation of immune memory and, therefore, immunization.
Activation of the innate immune system resulting in the production of cytokines during aging can be caused by waning control of latent infections, less effective physical barriers (more permeable skin, defective mucosal barriers in gut and respiratory systems) or increase in overall tissue damage [44, 45]. In addition, age-associated intrinsic defects in innate immune cells as well as accumulation and activation of non-immune cells such as adipocytes contribute to inflammaging.
The initiation of a T-cell response to a vaccine requires activation of dendritic cells that present antigenic fragment peptides derived from the vaccine to T cells. This process, which is the major target for the adjuvants in vaccines, appears to be disturbed in an inflammatory environment or with older dendritic cells. Understanding of the mechanisms of action of adjuvants and vaccine delivery systems and identifying those that are more effective in older individuals remain an area of active research [46, 47].
The adaptive immune response of T and B cells, the backbone of a vaccine response, is also susceptible to aging  and the previous decade has seen a surge in research on how and where this process is impaired in older individuals. Defects in adaptive T-cell responses already begin to become significant about the age of 50 years, in particular in individuals with comorbidities. However, at least for healthy individuals, the sizes and repertoires of antigen-specific CD4+ T cells and B cells do not appear to be decreased to a biologically relevant extent in older adults .
Instead, at least part of the problem seems to be the reduced ability of antigen-specific lymphocytes to survive as long-lived memory T cells . It is possible that chronic infections such as cytomegalovirus may compromise antigen-specific responses and help drive the development of immunosenescence [48, 49]. Whether this defect can be overcome by better vaccines or adjuvants or requires pharmacological intervention during the development of T-cell responses after vaccination remains uncertain. In contrast to CD4+ T cells, CD8+ naive and central memory T cells, apparently the weak link in immune aging, are increasingly lost and become dysfunctional with age . Depending on the infection targeted by vaccination, it might be advantageous to generate an effective CD8+ memory population earlier in life, but induction of a CD8+ T-cell response generally requires a live vaccine, whereas the inactivated or component vaccines previously developed preferentially induce CD4+ T-cell and B-cell responses.
The economics of adult vaccination
Alongside investments in infrastructure to improve water sanitation, vaccination programs are usually considered as the most important factor in improved public health and longevity worldwide over the last century. It is increasingly recognized that proper assessments of the economic value of vaccination needs to take a broader perspective than just focusing on the clinical benefits and the avoided healthcare costs that may be attributed to prevention of a single, specific disease. The broader economic benefits to consider and attempt to quantify include improved educational attainment, productivity gains from ameliorated effects of multi-morbidity on general health and cognition, community externalities and political stability [50, 51].
Intangible benefits of vaccination considered specifically in relation to vaccination of older adults, include attenuated severity of disease in breakthrough cases  and reductions in complications and comorbidities. Examples are studies showing that influenza and pneumococcal vaccinations may reduce the incidence of myocardial infarction by up to 50% . Another example is that herpes zoster is strongly associated with an increased risk of stroke, an excess risk which may be prevented by effective vaccines  (See Text Box 2).
Another consideration is that vaccination may diminish the problems related to polypharmacy in older adults with many comorbidities, which may lead to important adverse effects or lack of compliance . Another intangible benefit of vaccination, which is increasingly recognized (and not limited to vaccination of older adults), is that it may reduce the use of antibiotics [53,54,55] and thus diminish the growing problems caused by the development of antibiotic-resistant strains of bacteria. The United Kingdom Joint Committee on Vaccination and Immunization has recently recommended that this effect be included in economic evaluations of new vaccines and vaccination programs .
The most widely used approach to economic evaluation of healthcare interventions (including vaccines) is cost-effectiveness or cost-utility analyses, which aim to assess the incremental benefits of the intervention relative to its incremental costs, usually taking the perspective of the healthcare system in estimating the costs. This type of economic assessment is used in many countries by healthcare authorities for making decisions about reimbursement of new treatments. For preventive interventions like vaccines, the assessments usually seek to estimate the loss of utility (QoL) avoided by the intervention and relate this to the incremental costs incurred relative to no intervention. The result is expressed as the incremental costs per quality-adjusted life-year (QALY) gained (or, more accurately, not lost), which may then be compared to a benchmark to determine whether the intervention is cost-effective or not. Commonly used benchmarks in Europe range from 20,000 to 30,000 €/QALY, but few countries have set an explicit, official limit.
A number of economic evaluations and reviews of vaccination of older adults have recently been published, for example of pneumococcal conjugate vaccines  and herpes zoster vaccine [58, 59]. Generally, these evaluations conclude that vaccination is cost-effective but even taking the narrow direct cost perspective there are important challenges to meet when making such assessments. Among these are heterogeneity between targeted older individuals in terms of risk of infection, response to vaccination and severity of disease, just as there may be age-related variations in duration and level of immunity induced by vaccination .
It is also of interest to note that, ignoring the difficult assessment and valuation of health outcomes, studies of the costs of interventions show that the costs of vaccination are lower than those of many other preventive interventions and the potential benefits substantial (see Text Box 4). A recent study estimated that the total costs of fully adhering to recommended vaccinations over the full course of life in several European countries was much lower than those of many widely used preventive measures such as taking statins to prevent cardiovascular complications .
Adult vaccination: recommendations and coverage
Despite the accumulating evidence of the benefits of vaccination of older adults, vaccine uptake is generally limited and far below targets . To improve this situation, it is necessary to identify the barriers to increased uptake of vaccinations among older adults and to modify these where possible.
Vaccine programs for children and younger adults have shown that great declines in the incidence of infectious diseases can be achieved if vaccination is properly implemented . In the United States, coverage rates in children for most recommended vaccines reach approximately 90% . European countries are more diverse, both in their recommended vaccines and the recommended schedules, but the coverage for the most common pediatric vaccines (measles, diphtheria, pertussis, tetanus, tuberculosis, polio, etc.) reaches or exceeds 90% in most EU countries . These programs indicate what is needed for successful disease control by vaccination and thus demonstrate the opportunities for adult vaccination programs. Comparing current pediatric vaccination programs with what is being done to enhance vaccination of older adults also highlights important differences and the challenges that must be overcome to improve adult vaccination rates.
Where adult vaccination is recommended, there are wide divergences in what is recommended (Table 1) and in the coverage levels reached. In a recent survey of immunization policies in 31 high-income countries , only 12 had comprehensive adult vaccination policies, although all of them had recommendations for at least one adult vaccination (influenza, with programs in place to monitor the vaccination coverage in adults in 29 of the countries). In two countries, influenza vaccination is recommended for the entire population, whereas in the rest it was only recommended for risk groups. Despite recommendations and public funding, only one country in this study (the Netherlands) exceeded the recommended level of coverage (75%) while many reached less than 50% . For the other vaccines, recommendations are most common (26–27 countries) for adult immunization against hepatitis B, pneumococcus, tetanus and diphtheria, although again, these recommendations primarily focus on risk groups and travelers  and coverage is generally poor . Overall, the picture of adult vaccination is one of fragmented recommendations, restricted coverage , and significant data gaps .
Adult vaccination: building effective programs
To understand why adult vaccination coverage is low, it is useful to examine those countries that have achieved the highest coverage and also to compare adult vaccination programs with pediatric vaccination programs. Successful pediatric vaccination programs generally recommend universal vaccination, they are supported by effective funding mechanisms, and the outcomes are assessed (and the programs corrected, if needed) based on routine surveillance of disease and vaccination coverage.
The important role of recommendations is suggested by the observation that countries with comprehensive vaccination recommendations for older adults tend to include more vaccines in their programs  and to reach higher levels of coverage with the recommended vaccines . In addition, there is evidence that vaccination recommendations focusing on groups at risk, although apparently offering an efficient approach to vaccination, may actually inhibit uptake, since they may inadvertently send the message that the national health system does not see the recommended vaccines as important . However, this evidence must be critically assessed in the light of economic evaluations, which often conclude that universal vaccination of older adults against a particular VPD is not cost-effective and that programs must be targeted to specific, well-characterized groups to ensure acceptable incremental costs per QALY gained .
As all the evidence identifies provider recommendation as the principal reason for adults to become vaccinated , this implies that if few providers are convinced of the importance of adult vaccination the uptake will remain low. Numerous studies show that many primary-care physicians do not consider vaccination of older adults a high priority [81,82,83,84,85].
Without funding, however, recommendations have limited effect. While most high-income countries have some form of public funding in place for recommended vaccines , cost can still be a barrier to access and may discourage HCPs from recommending the vaccine. As one example illustrating this, moving from a partial to a full subsidy of pneumococcal vaccination for older adults in Australia raised the uptake from 39 to 73% in patients attending a large public hospital . Similarly, pediatric vaccination in the United States is financially supported by the Vaccines for Children initiative and this has virtually eliminated previously significant regional, ethnic and socioeconomic disparities in vaccination coverage . In contrast, the same vaccines for adults can require substantial copayments, and ethnic and socioeconomic disparities in coverage rates are clearly visible .
These findings suggest that four things are necessary to support effective vaccination programs, both in children and in adults (Fig. 2). First, a clear commitment to vaccination must be reflected in a coherent, comprehensive public policy. Second, a commitment to fund and deliver vaccines to the population is required, whether via predominantly public funds as in the United Kingdom and the Netherlands, or a mixture of public and private funds as in the United States. Third, effective surveillance of vaccination coverage and the burden of disease is required, so that goals can be set, priorities established, and the effectiveness of the program monitored and adjusted, if necessary. Finally, the safety and value of vaccination must be understood and appreciated both by the target population and by vaccinating healthcare professionals.
The first three of these factors can be implemented by public policy and the initial steps have already been taken in many countries. However, for adult vaccination programs to achieve the same kind of success as pediatric programs have, they need a similar degree of population acceptance. This is particularly an issue for adult vaccination because there is a widespread public perception that vaccination is not needed  and the decision of the individual to seek or accept vaccination is crucial. For infant vaccination, the messages are targeted at the parents. For adult vaccination, the vaccine recipients must be reached with a message that can convince them of the value and safety of vaccination directly to themselves or to their family. Additionally, it is important that vaccinating healthcare personnel understand the value of vaccination both for themselves and for patients.
These considerations are supported by interventions that have been associated with substantial improvements in adult vaccination coverage [88, 89]. Important common elements to improve coverage seem to be: clear national objectives and commitments; incentives for healthcare personnel to vaccinate; vaccination reimbursement systems; information and awareness campaigns; clear coverage objectives. However, even programs considered as highly successful often plateau at a suboptimal level of coverage . These plateaus vary between vaccine types thereby indicating that vaccine-specific issues must be addressed as well.
All over the world, in rich and developing countries alike, a demographic shift towards an aging population is underway. How we handle aging populations will have major economic and healthcare implications in the next few decades. Many infectious diseases inflict a disproportionate burden of disease in older adults and can contribute to the onset of frailty, but may be prevented or attenuated by vaccination. This implies that vaccination can serve as the third pillar of a strategy to support healthy aging, alongside healthy diet and exercise. However, the uptake of vaccination by the target population is generally low and must be substantially improved if the potential of vaccines to reduce the morbidity, mortality, loss of quality of life and healthcare costs caused by VPDs is to be realized . The available evidence indicates that vaccination coverage in older adults can be considerably improved, although there is a need for further research into the generalizability of particular interventions to improve coverage.
Quality of life
Vaccine preventable disease
Tan L (2015) Adult vaccination: now is the time to realize an unfulfilled potential. Human Vacc Immunother 9:2158–2166
Suhrcke M, McKee M, Sauto Arce R, Tsolova S, Mortensen J. The contribution of health to the economy in the European Union. European Communities, Luxembourg 2005. https://ec.europa.eu/health/archive/ph_overview/documents/health_economy_en.pdf. Last accessed 6 Feb 2018
European Commission, Directorate-General for Economic and Financial Affairs. Sustainability Report. Brussels, 2009. http://ec.europa.eu/economy_finance/publications/pages/publication15998_en.pdf. Last accessed 6 Feb 2018
World Health Organization. WHO report on healthy aging. Geneva 2015. http://apps.who.int/iris/bitstream/10665/186463/1/9789240694811_eng.pdf. Last accessed 6 Feb 2018
Fried LP, Tangen CM, Walston J et al (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Bio Sci Med Sci 56:M146–M156
Vellas B, Cesari M, Li J (Eds). White book on frailty. 2017. http://www.garn-network.org/documents/WHITEBOOKONFRAILTY-USVERSION.pdf. Last accessed 31 Mar 2017
Bula CJ, Ghiraldi G, Weitlisbach V et al (2004) Infections and functional impairment in nursing home residents: a reciprocal relationship. J Am Geriatr Soc 52:700–706
Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJL (2006) Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 367:1447–1457
Yoshikawa TT (1997) Perspective: aging and infectious diseases: past, present, and future. J Infect Dis 176:1053–1057
McLaughlin JM, McGinnis JJ, Tan L, Mercatante A, Fortuna J (2015) Estimated human and economic burden of 4 major adult vaccine-preventable diseases in the US, 2013. J Prim Prev 36:259–273
Office of Disease Prevention and Health Promotion. Immunization and infectious diseases. https://www.healthypeople.gov/2020/topics-objectives/topic/immunization-and-infectious-diseases. Last accessed 31 Mar 2017
Ozawa S, Portnoy A, Getaneh H, Clark S, Knoll M, Bishai D et al (2016) Modeling the economic burden of adult vaccine-preventable diseases in the United States. Health Aff 35:2124–2132
Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G (2004) Untangling the concepts of disability, frailty and comorbidities: implications for improved targeting and care. J Gerontol A Bio Sci Med Sci 59:255–263
Bergman H, Ferrucci L, Guralnik J et al (2007) Frailty: an emerging research and clinical paradigm—issues and controversies. J Gerontol A Biol Sci Med Sci 62:731–737
Fulop T, McElhaney J, Pawelec G et al (2015) Frailty, inflammation and immunosenescence. Interdiscip Top Gerontol Geriatr 41:26–40
Johnstone J, Parsons R, Botelho F, Millar J, McNeil S, Fulop T et al (2014) Immune biomarkers predictive of respiratory viral infection in elderly nursing home residents. PLoS One 9:e108481
Johnstone J, Parsons R, Botelho F, Millar J, McNeil S, Fulop T et al (2017) T-cell phenotypes predictive of frailty and mortality in elderly nursing home residents. J Am Geriatr Soc 65:153–159
McElhaney JE, Kuchel GA, Zhou X, Swain SL, Haynes L (2016) T-cell immunity to influenza in older adults: a pathophysiological framework for development of more effective vaccines. Front Immunol. https://doi.org/10.3389/fimmu.2016.00041
Puthanakit T, Huang LM, Chiu CH, Tang RB, Schwarz TF, Esposito S et al (2016) Randomized open trial comparing 2-dose regimens of the human papillomavirus 16/18 AS04-adjuvanted vaccine in girls aged 9–14 years versus a 3-dose regimen in women aged 15–25 years. J Infect Dis 214:525–536
Iversen OE, Miranda MJ, Ulied A, Soerdal T, Lazarus E, Chokephaibulkit K et al (2016) Immunogenicity of the 9-valent HPV vaccine using 2-dose regimens in girls and boys vs a 3-dose regimen in women. JAMA 316:2411–2421
Lang PO, Aspinall R (2014) Vaccination in the elderly: what can be recommended? Drugs Aging 31:581–599
Preaud E, Durand L, Macabeo B, Farkas N, Sloesen B, Palache A et al (2014) Annual public health and economic benefits of seasonal influenza vaccination: a European estimate. BMC Public Health 14:813
Reed C, Meltzer MI, Finelli L, Fiore A (2012) Public health impact of including two lineages of influenza B in a quadrivalent seasonal influenza vaccine. Vaccine 30:1993–1998
Lee BY, Bartsch SM, Willing AM (2012) The economic value of a quadrivalent versus trivalent influenza vaccine. Vaccine 30:7443–7446
Andre FE, Booy R, Bock HL, Clemens J, Datta SK, John TJ et al (2008) Vaccination greatly reduce disease, disability, death and inequity worldwide. Bull World Health Organ 86:140–146
Schmader KE, Johnson GR, Saddier P, Ciarleglio M, Wang WW, Zhang JH et al (2010) Effect of a zoster vaccine on herpes zoster-related interference with functional status and health-related quality of life measures in older adults. J Am Geriatr Soc 58:1634–1641
Pickering G, Marcoux M, Chapiro S, David L, Rat P, Michel M et al (2016) An algorithm for neuropathic pain management in alder people. Drugs Aging 33:575–583
Drolet M, Brisson M, Schmader KE, Levin MJ, Johnson R, Oxman MN et al (2010) The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: a prospective study. CMAJ. https://doi.org/10.1503/cmaj.091711
Kang JH, Ho JD, Chen YH, Lin HC (2009) Increased risk of stroke after a herpes zoster attack. Stroke 40:3443–3448
Johnson RW, Bouhassira D, Kassianos G, Leplege A, Schmader KE, Weinke T (2010) The impact of herpes zoster and post-herpetic neuralgia on quality-of-life. BMC Med 8:37
Hung IF, Leung AY, Chu DW, Leung D, Cheung T, Chan CK et al (2010) Prevention of acute myocardial infarction and stroke among elderly persons by dual pneumococcal and influenza vaccination: a prospective cohort study. Clin Infect Dis 51:1007–1016
Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ et al (2003) Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289:179–186
Black S, De Gregorio E, Rappuoli R (2015) Developing vaccines for an aging population. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aaa0722
Goronzy JJ, Weyand CM (2013) Understanding immunosenescence to improve responses to vaccines. Nat Immunol 14:428–436
Goronzy JJ, Fang F, Cavanagh MM, Qi Q, Weyand CM (2015) Naïve T cell maintenance and function in human aging. J Immunol 194:4073–4080
Kim C, Fang F, Weyand CM, Goronzy JJ (2017) The life cycle of a T cell after vaccination—where does immune ageing strike? Clin Exp Immunol 187:71–81
Briceno O, Lissina A, Wanke K, Afonso G, von Braun A, Ragon K et al (2016) Reduced naïve CD8(+) T-cell priming efficacy in elderly adults. Aging Cell 15:14–21
Chlibek R, Pauksens K, Rombo L, van Rijckevorsel G, Richardus JH, Plassmann G et al (2016) Long-term immunogenicity and safety of an investigational herpes zoster subunit vaccine in older adults. Vaccine 34:863–868
Cunningham AL, Lal H, Kovac M, Chlibek R, Hwang SJ, Díez-Domingo J et al (2016) Efficacy of the herpes zoster subunit vaccine in adults 70 years of age or older. N Engl J Med 375:1019–1032
Seo YB, Choi WS, Lee J, Song JY, Cheong HJ, Kim WJ (2014) Comparison of the immunogenicity and safety of the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines in the elderly. Clin Vaccine Immunol 21:989–996
Van Buynder PG, Konrad S, Van Buynder JL, Brodkin E, Krajden M, Ramler G et al (2013) The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine 31:6122–6128
Marti M, de Cola M, MacDonald NE, Dumolard L, Duclos P (2017) Assessments of global drivers of vaccine hesitancy in 2011—looking beyond safety concerns. PLoS One 12:e0172310
Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69:S4–S9
Pinti M, Appay V, Campisi J (2016) Aging of the immune system: focus on inflammation and vaccination. Eur J Immunol 46:2286–2301
Shaw AC, Goldstein DR, Montgomery RR (2013) Age-dependent dysregulation of innate immunity. Nat Rev Immunol 13:875–887
Coffman RL, Sher A, Seder RA (2010) Vaccine adjuvants: putting innate immunity to work. Immunity 33:492–503
Gupta S (2014) Role of dendritic cells in innate and adaptive immune response. Exp Gerontol 54:47–52
Solana R, Tarazona R, Aiello AE, Akbar AN, Appay V, Beswick M et al (2012) CMV and immunosenescence: from basics to clinics. Immun Aging 9:23
Derhovanessian E, Maier AB, Hähnel K, McElhaney JE, Slagboom EP, Pawelec G (2014) Latent infection with cytomegalovirus is associated with poor memory CD4 responses to influenza A core proteins in the elderly. J Immunol 193:3624–3631
Bärnighausen T, Berkley S, Bhutta ZA, Bishai DM, Black MM, Bloom DE et al (2014) Reassessing the value of vaccines. Lancet Glob Health. https://doi.org/10.1016/s2214-109x(13)70170-0
Bloom DE (2015) Valuing vaccines: deficiencies and remedies. Vaccine 33S:B29–B33
Bonanni P, Picazo JJ, Remy V (2015) The intangible benefits of vaccination—what is the true economic value of vaccination? J Market Access Health Policy. https://doi.org/10.3402/jmahp.v3.26964
Kwong JC, Maaten S, Upshur RE, Patrick DM, Marra F (2009) The effect of universal influenza immunization on antibiotic prescriptions: an ecological study. Clin Infect Dis 49:750–756
Lipsitch M, Siber GR (2016) How can vaccines contribute to solving the antimicrobial resistance problem? MBio 7:e00428-16
Palmu AA, Jokinen N, Nieminen H, Rinta-Kokko H, Ruokokoski E, Puumalainen T et al (2014) Effect of pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) on outpatient antimicrobial purchases: a double-blind, cluster randomised phase 3–4 trial. Lancet Infect Dis 14:205–212
Joint Committee on Vaccination and Immunisation. Minutes of the meeting on 1 October 2014. https://app.box.com/s/iddfb4ppwkmtjusir2tc/1/2199012147/22846051967/1. Last accessed 31 Mar 2017
Dirmesropian S, Wood JG, MacIntyre CR, Newall AT (2015) A review of economic evaluations of 13-valent pneumococcal conjugate vaccine (PCV-13) in adults and elderly. Hum Vaccin Immunother 11:818–825
Dirmesropian S, Wood JG, MacIntyre CR, Beutels P, Newall AT (2016) Economic evaluation of vaccination programmes in older adults and the elderly: important issues and challenges. Pharmacoeconomics 34:723–731
Kawai K, Preaud E, Baron-Papillon F, Largeron N, Acosta CJ (2014) Cost-effectiveness of vaccination against herpes zoster and postherpetic neuralgia: a critical review. Vaccine 32:1645–1653
Ethgen O, Cornier M, Chriv E, Baron-Papillon F (2016) The cost of vaccination throughout life: a western European overview. Human Vaccin Immunother 12:2029–2037
Szucs TD, Pfeil AM (2013) A systematic review of the cost effectiveness of herpes zoster vaccination. Pharmacoeconomics 31:125–136
Murray CJ, Lopez AD (1997) Alternative projections of mortality and disability by cause 1990–2020: global burden of disease study. Lancet 349:1498–1504
Maggi S (2010) Vaccination and healthy aging. Expert Rev Vaccines 9(3 Suppl):3–6
Michel JP, Lang PO (2011) Promoting life course vaccination. Rejuvenation Res 14:75–81
Ministry of Health, Labour and Welfare. [For people, for life, for the future.] (in Japanese) Tokyo 2016. http://www.mhlw.go.jp/file/04-Houdouhappyou-12401250-Hokenkyoku-Iryouhitekiseikataisakusuishinshitsu/0000019922.pdf. Last accessed 31 Mar 2017
Centers for Disease Control and Prevention. Black CL, Yankey D, Kolasa M. National, state and local area vaccination coverage among children aged 19–35 months—United States, 2012. MMWR 2013;62:733–737. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6236a1.htm. Last accessed 6 Feb 2018
Harris JB, Gacic-Dobo M, Eggers R, Brown DW, Sodha SV (2014) Global routine vaccination coverage, 2013. MMWR 63:1055–1058
Wu LA, Kanitz E, Crumly J, D’Ancona F, Strikas RA (2013) Adult immunization policies in advanced economies: vaccination recommendations, financing and vaccination coverage. Int J Public Health 58:865–874
Kanitz EE, Wu LA, Giambi C, Strikas RA, Levy-Bruhl D, Stefanoff P et al (2012) Variation in adult vaccination policies across Europe: an overview from VENICE network on vaccine recommendations, funding and coverage. Vaccine 30:5222–5228
Williams WW, Lu PJ, O’Halloran A, Kim DK, Grohskopf LA, Pilishvili T et al (2016) Surveillance of vaccination coverage among adult populations—United States 2014. MMWR 65:1–36
Weinberger B (2018) Vaccines for the elderly: current use and future challenges. Immun Aging 15:3. https://doi.org/10.1186/s12979-017-0107-2[PMC5778733]
European Centre for Disease Prevention and Control. Types of seasonal influenza vaccine. https://ecdc.europa.eu/en/seasonal-influenza/prevention-and-control/vaccines/types-of-seasonal-influenza-vaccine. Last accessed 6 Feb 2018
Federal Office of Public health and Federal Vaccination Commission. [Swiss vaccination plan in 2017. Directives et recommandations.] (in German). Bern 2017. https://www.bag.admin.ch/dam/bag/de/dokumente/mt/i-und-b/richtlinien-empfehlungen/allgemeine-empfehlungen/schweizerischer-impfplan.pdf.download.pdf/schweizerischer-impfplan-de.pdf. Last accessed 6 Feb 2018
Australian Government Department of Health. National Immunisation Program Schedule. 2016. http://immunise.health.gov.au/internet/immunise/publishing.nsf/Content/5403D77C07E1973ACA257D49001E3775/$File/NIP-schedule2016.pdf. Last accessed 6 Feb 2018
New Zealand Ministry of Health. New Zealand immunisation schedule. 2017. https://www.health.govt.nz/our-work/preventative-health-wellness/immunisation/new-zealand-immunisation-schedule. Last accessed 6 Feb 2018
Infectious Disease Surveillance Center of National Institute of Infectious Diseases. Routine/voluntary immunization schedule in Japan. 2016. https://www.niid.go.jp/niid/images/vaccine/schedule/2016/EN20161001.pdf. Last accessed 6 Feb 2018
Berger S (2017) Infectious diseases of South Korea, 2017th edn. GIDEON Informatics, Inc, Los Angeles
The Federal Public Service (FPS) Health, Food Chain Safety and Environment. Advisory report 9209—vaccination against herpes zoster virus (Zona). 2017. https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/9209_shc_advice_9209_zonaa5_pdt.pdf. Last accessed 6 Feb 2018
Swanson KA, Schmitt HJ, Jansen KU, Anderson AS (2015) Adult vaccination: current recommendations and future prospects. Human Vaccin Immunother 11:150–155
van Hoek AJ, Miller E (2016) Cost-effectiveness of vaccinating immunocompetent ≥ 65 year olds with the 13-valent pneumococcal vaccine in England. PLoS One. https://doi.org/10.1371/journal.pone.0149540
Badertscher N, Morell S, Rosemann T, Tandjung R (2012) General practitioners’ experiences, attitudes, and opinions regarding the pneumococcal vaccination for adults: a qualitative study. Int J Gen Med 5:967–974
Bödecker B, Remschmidt C, Schmidt P, Wichmann O (2015) Why are older adults and individuals with underlying chronic diseases in Germany not vaccinated against flu? A population-based study. BMC Public Health. https://doi.org/10.1186/s12889-015-1970-4
Eilers R, Krabbe PF, de Melker HE (2015) Attitudes of Dutch general practitioners towards vaccination the elderly: less is more? BMC Fam Pract. https://doi.org/10.1186/s12875-015-0377-8
Elkin Z, Cohen EJ, Goldberg JD, Gillespie C, Li X, Jung J, Cohen M et al (2013) Studying physician knowledge, attitudes, and practices regarding the herpes zoster vaccine to address perceived barriers to vaccination. Cornea 32:976–981
Klett-Tammen CJ, Krause G, von Lengerke T, Castell S (2016) Advising vaccinations for the elderly: a cross-sectional survey on differences between general practitioners and physician assistants in Germany. BMC Fam Pract. https://doi.org/10.1186/s12875-016-0502-3
Ridda I, MacIntyre RC, Lindley RI, McIntyre PB, Sullivan J, Gilbert G et al (2007) Predictors of pneumococcal vaccination uptake in hospitalized patients aged 65 years and over shortly following the commencement of a publicly funded national pneumococcal vaccination program in Australia. Human Vaccin 3:83–86
Walker AT, Smith PJ, Kolasa M; Centers for Disease Control and Prevention. Reduction of racial/ethnic disparities in vaccination coverage, 1995–2011. MMWR 2014;63:7–12. https://www.cdc.gov/mmwr/preview/mmwrhtml/su6301a3.htm. Last accessed 6 Feb 2018
Blank P, Schwenkglenks M, Szucs TD (2012) The impact of European vaccination policies on seasonal influenza vaccination coverage rates in the elderly. Hum Vaccin Immunother 8:328–335
Yang TU, Kim E, Park YJ, Kim D, Kwon YH, Shin JK et al (2016) Successful introduction of an underutilized elderly pneumococcal vaccine in a national immunization program by integrating the pre-existing public health infrastructure. Vaccine. https://doi.org/10.1016/j.vaccine.2016.01.043
Johnson DR, Nichol KL, Lipczynski K (2008) Barriers to adult immunization. Am J Med 121(Suppl2):S28–S35
The authors would like to thank Nobuhiro Noro for his essential part in the success of the original meeting at which this manuscript originated. The authors also thank Business & Decision Life Sciences platform for editorial assistance and manuscript coordination, on behalf of GSK. Carole Desiron coordinated the manuscript development and gave editorial support. The authors also thank Niels Neymark, freelance scientific writer on behalf of GSK for providing medical writing support.
GlaxoSmithKline Biologicals S.A. funded this study and all costs related to the development of this publication.
Conflict of interest
GDG, ADP, RSO and MD are employees of the GSK group of companies. ADP, RSO and MD hold restricted shares in the GSK group of companies. MC received personal fees from the GSK group of companies. JEM is an employee of The Health Sciences North Research Institute and her institution received an honorarium from the GSK group of companies for her attendance at an advisory board meeting and she received travel reimbursement during the conduct of this work and outside this work. PHL, BGL and JF have nothing to disclose. EW received consulting fees from Alios Pharmaceuticals outside this work. JG received grants from NIH during the conduct of this work and received personal fees from the GSK group of companies for his attendance at an advisory board meeting during the conduct of this work. SM received personal fees from the GSK group of companies for her participation in a vaccine workshop in Brussels, Belgium, in February 2016 outside this work and received a grant from Takeda outside this work. WS received a grant from Centers for Disease Control and Prevention during the conduct of this work. WS also received personal fees from Merck, Pfizer, Genentech, Dynavax and Novavax during the conduct of this work. HN received personal fees from the GSK group of companies for his attendance at an advisory board meeting during the conduct of this work and received personal fees from Pfizer and MSD outside of this work.
All procedures performed in this study were in accordance with the ethical standards.
For a literature review, written consent is not required.
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Doherty, T.M., Connolly, M.P., Del Giudice, G. et al. Vaccination programs for older adults in an era of demographic change. Eur Geriatr Med 9, 289–300 (2018). https://doi.org/10.1007/s41999-018-0040-8