Send Orders for Reprints to reprints@benthamscience.net Current Topics in Medicinal Chemistry, 2013, 13, 000-000 1 1568-0266/13 $58.00+.00 © 2013 Bentham Science Publishers Immune Senescence and Vaccination in the Elderly Pierre Olivier Lang 1,2, *, Sheila Govind 1 , Annemieke ten Bokum 1 Natalie Kenny 1 , Emmanuel Matas 1 , David Pitts 1 and Richard Aspinall 1 1 Translational Medicine Research group, Cranfield Health, Cranfield University, Cranfield, UK; 2 Nescens Centre of preventive medicine, Clinique of Genolier, Switzerland Abstract: Vaccines are powerful public health tools that have been of tremendous benefit in protecting vulnerable popu- lations worldwide from many pathogens. However, vaccine- preventable diseases still remain a considerable burden and this is particularly true among aging and aged populations in industrialized countries. The predicted demographic shift in the population landscape towards an ever-increasing aging population and the evidence suggesting that older individuals mount less-than optimal immune response to vaccination have raised the question of improving vaccine responses in older individuals. This review presents recent progress in the understanding at the cellular and molecular levels of age related immune decline and strategies to translate current knowledge into the development of immunization strategies to promote healthy aging, keeping older members of our society autonomous and independent. Keywords: Healthy aging, immunosenescence, older adults, vaccination, vaccine design, vaccine development, vaccine effec- tiveness. 1. INTRODUCTION Advances in medicine, socioeconomic development, and declining fertility have all contributed to the wellbeing of mankind and consequently to the ageing of the global popu- lation [1, 2]. Demographic studies show changes in the pro- portions of the different age groups in the population begin- ning with a decrease in the proportion of young people. Sub- sequently this was followed by a large increase in the work- ing age group leading to an inescapable increase in the oldest age group [3]. By the year 2030, the percentage of the popu- lation that will be elderly (60 years of age) is predicted to represent over 25% of the population worldwide [4, 5]. Five years from now, for the first time in history, the number of people aged 65 years and older will outnumber children younger than 5 years [6]. Whilst the ageing of the general population is one of hu- manity’s greatest triumphs [2], it also confronts societies with enormous medical challenges [5]. If ageing is to be considered as a positive experience, living longer must be accompanied by continuing opportunities for health, social participation and security [7]. However, lengthening lifespan is not necessarily synonymous with extending life expec- tancy in good health. Studies in the United States suggested that chronic and degenerative disorders become more and more prevalent with advancing age and that multi-morbidity is increasing [8]. The progressive decline with age in a dis- ability-free life is associated with an increase in the require- ment for assisted living among older individuals in order for them to perform basic activities of daily living [9, 10]. *Address correspondence to this author at the Nescens Centre of preventive medicine c/o Clinique of Genolier – Rue du Muids, 3 – CH-1272 Genolier, Switzerland; Tel: +41 (0) 22.366.90.00; Fax: +41(0) 22.366.90.11; E-mail: polang@nescens.com The significant increase in human longevity has thus raised issues associated with healthy aging. Since infec- tious diseases contribute significantly not only to morbidity and mortality, but also to dependency and institutional ad- mission in the aging and older adult population [11-14], strategies for preventing these diseases would have a clear impact on improving healthy aging. Older individuals show an increased susceptibility to infection and whilst the age- related decline of the immune system partly explains this susceptibility [15], other factors include nutritional status [16-20], sarcopenia [21], hormonal dysregulation [22, 23], and the impact of comorbidities [24]. The list is not com- plete, underlining our poor understanding of the mecha- nisms of the inability of the aged body to deal with new and previously encountered pathogens [15]. Vaccines are one of the most powerful public health tools with proven benefits in protecting vulnerable population against numer- ous pathogens, but tailored vaccines and immunization strategies for the senior population still need to be devel- oped to counteract the waning of immune responsiveness and to restore a competent immune response [25, 26]. Be- cause vaccination seems to be much less effective in older adults compared to their younger counterparts [27-31], vaccines specifically directed to the elderly are becoming a major public health priority and this is true both in devel- oped and developing countries [14]. The aim of this review is to present recent advances in the understanding at the cellular and molecular levels of immune senescence and strategies by which progress made can be integrated to translate the current knowledge into the development of immunization strategies to maintain seniors in good health and keep them autonomous and independ- ent.