Immunosenescence: influenza vaccination and the elderly
Introduction
According to the United Nations Population Division, the number of elderly persons is expected to increase from 600 million currently to nearly 2 billion worldwide by 2050; in developed countries 25% of the population will be older than 65 years because of advances in average life expectancy [1]. Influenza directly or indirectly contributes to the four leading causes of global mortality, at rates that are highest in older adults. Currently, between 250 000 and 500 000 influenza-related deaths occur annually in the 65+ years of age population worldwide. Given this trend, emphasis on the overall quality of life of the older person represents a major public health challenge and is now a global issue.
Improving protective measures in the aging population has been identified as a public health priority by the World Health Organization [2]. Vaccination has been the primary means of protection and over time can promote global eradication of the infections. However, we face some challenges related to aging of the population and the effects of immunosenescence (Figure 1). As a consequence, there has been a shift in the current research focus of vaccine biology to now emphasize the importance of understanding the mechanisms of immune aging and improving vaccine efficacy to counter the effects of immunosenescence.
Section snippets
Immunosenescence and inflammaging
Although there is no universal definition of aging, the effectiveness of several molecular and physiological systems including the immune system becomes compromised, both quantitatively and qualitatively. The two terms, immunosenescence and inflammaging, may sound contradictory; however we will describe how they are intertwined. ‘Immunosenescence’ is the biological aging process associated with progressive decline in systemic immunity and increased prevalence of cancer, autoimmune and chronic
Vaccination in the elderly
Since infections are a major cause of morbidity and mortality in the elderly, vaccination would be the most cost-effective strategy to control and eradicate infections. According to the Centers of Disease Control and Prevention (CDC), five vaccines are now recommended for people over 60 years of age to protect them against seasonal influenza, tetanus, diphtheria, pertussis, pneumococcal diseases and shingles [10]. Although vaccines may not provide complete protection, they do induce partial
Progress toward improving vaccines
With the emergence of the zoonotic swine influenza A H1N1 (pdmH1N1) and avian influenza viruses (H5N1, H7N9), the need to develop effective influenza vaccines that have the capability to maximize cross-protective immunogenicity is a global health priority. The current trivalent influenza vaccines (TIV) include two influenza A strains (H1N1, H3N2) and one B strain, and are produced as split-virus vaccines (SVV) including all of the viral proteins, or subunit vaccines (SuV) which include only
Future
The age-associated changes in the immune system occur in different people at different rates. For the future we may need to consider a more ‘personalized’ approach to vaccine design targeting certain high-risk groups such as the 65+ population. Emphasis on the dual targeting of vaccine formulations, engaging both the innate and adaptive arms of the immune system, is crucial for improving vaccine efficacy. Some areas of focus for an optimized vaccination strategy in older adults would include
Conclusion
The elderly population accounts for more than 90% of seasonal influenza-related deaths and hospitalizations. While current vaccines are highly effective in younger adults, they are much less effective in the elderly due to immunosenescence. Weakened T cell help, and decreased B cell and cytotoxic T cell responses, all culminate in unproductive priming and recall responses to vaccination in older adults. A greater understanding of these basic mechanisms of immunosenescence and alternate
Conflict of interest
Janet McElhaney has participated on advisory boards for GlaxoSmithKline, Sanofi Pasteur, Novartis, and Med-Immune, on data monitoring boards for Sanofi Pasteur, and has participated in clinical trials sponsored by Merck, GlaxoSmithKline and Sanofi Pasteur; and has received honoraria and travel and accommodation reimbursements for presentations sponsored by Merck, GlaxoSmithKline and Sanofi Pasteur, and travel reimbursement for participation on a publication steering committee for
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
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