At the start of the 21st century, seasonal influenza virus infection is still a major public health concern across the world. The recent body of evidence confirms that trivalent inactivated influenza vaccines (TIVs) are not optimal within the population who account for approximately 90% of all influenza-related death: elderly and chronically ill individuals regardless of age. With the ever increasing aging of the world population and the recent fears of any pandemic influenza rife, great efforts and resources have been dedicated to developing more immunogenic vaccines and strategies for enhancing protection in these higher-risk groups. This paper describes the mechanisms that shape immune response at the extreme ages of life and how they have been taken into account to design more effective immunization strategies for these vulnerable populations. Furthermore, consideration will be given to how herd immunity may provide an effective strategy in preventing the burden of seasonal influenza infection within the aged population. 1. Introduction Infants and the elderly share a high vulnerability to infections and therefore have specific immunization requirement [1]. Foremost amongst vaccine infectious preventable diseases is influenza virus infection. Worldwide influenza causes 3–5 million of severe cases per year resulting in 250,000–350,000 deaths [2]. Indeed, while influenza affects people of all ages, young children and older adults, suffering or not from medical comorbid conditions, are particularly vulnerable. This results in increased morbidity and mortality [2–4]. While children have the highest rates of seasonal influenza infection and illness [3, 4], mortality in the elderly is just the tip of the iceberg in terms of disease burden. Influenza infection can also act within this population as a trigger for functional decline, decompensation of medical comorbid conditions, and/or cardiovascular and neurovascular acute diseases, being thus contributory to excessive hospitalization, antibiotic prescriptions, and a considerable economic burden [5–10]. Indeed, early immune protection initially relies on maternal antibodies, and this makes infants to become vulnerable to infections within a short time frame if failure of development of adaptive immunity in order to confer sustained protection [1, 11]. In those who approach the end of the normal life expectancy, the age-related decline in immune function, usually termed immunosenescence, partly explains the inability to resist influenza virus. Moreover, the elderly not only have problems in dealing with new
References
[1]
E. R. Moxon and C. A. Siegrist, “The next decade of vaccines: societal and scientific challenges,” The Lancet, vol. 378, no. 9788, pp. 348–359, 2011.
[2]
World Health Organization, “Influenza vaccines,” The Weekly Epidemiological Record, vol. 80, no. 33, pp. 279–287, 2005.
[3]
K. A. Poehling, K. M. Edwards, G. A. Weinberg et al., “The underrecognized burden of influenza in young children,” The New England Journal of Medicine, vol. 355, no. 1, pp. 31–40, 2006.
[4]
W. J. Paget, C. Balderston, I. Casas et al., “Assessing the burden of paediatric influenza in Europe: the European Paediatric Influenza Analysis (EPIA) project,” European Journal of Pediatrics, vol. 169, no. 8, pp. 997–1008, 2010.
[5]
A. S. Monto, F. Ansaldi, R. Aspinall et al., “Influenza control in the 21st century: optimizing protection of older adults,” Vaccine, vol. 27, no. 37, pp. 5043–5053, 2009.
[6]
J. E. McElhaney, “The unmet need in the elderly: designing new influenza vaccines for older adults,” Vaccine, vol. 23, supplement 1, pp. S10–S25, 2005.
[7]
G. Gavazzi and K. H. Krause, “Ageing and infection,” Lancet Infectious Diseases, vol. 2, no. 11, pp. 659–666, 2002.
[8]
P. O. Lang, S. Govind, W. A. Mitchell et al., “Influenza vaccine effectiveness in aged individuals: the role played by cell-mediated immunity,” European Geriatric Medicine, vol. 1, no. 4, pp. 233–238, 2010.
[9]
P. O. Lang, S. Govind, W. A. Mitchell, C. A. Siegrist, and R. Aspinall, “Vaccine effectiveness in older individuals: what has been learned from the influenza-vaccine experience,” Ageing Research Reviews, vol. 10, no. 3, pp. 389–395, 2011.
[10]
N. A. Molinari, I. R. Ortega-Sanchez, M. L. Messonnier et al., “The annual impact of seasonal influenza in the US: measuring disease burden and costs,” Vaccine, vol. 25, no. 27, pp. 5086–5096, 2007.
[11]
C. A. Siegrist and R. Aspinall, “B-cell responses to vaccination at the extremes of age,” Nature Reviews Immunology, vol. 9, no. 3, pp. 185–194, 2009.
[12]
D. Weiskopf, B. Weinberger, and B. Grubeck-Loebenstein, “The aging of the immune system,” Transplant International, vol. 22, no. 11, pp. 1041–1050, 2009.
[13]
R. Aspinall, D. Pitts, A. Lapenna, and W. Mitchell, “Immunity in the elderly: the role of the thymus,” Journal of Comparative Pathology, vol. 142, supplement 1, pp. S111–S115, 2010.
[14]
Centers for Disease Control and Prevention, “Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP),” Morbidity and Mortality Weekly Report, vol. 53, no. 6, pp. 1–40, 2004.
[15]
K. Goodwin, C. Viboud, and L. Simonsen, “Antibody response to influenza vaccination in the elderly: a quantitative review,” Vaccine, vol. 24, no. 8, pp. 1159–1169, 2006.
[16]
L. Simonsen, R. J. Taylor, C. Viboud, M. A. Miller, and L. A. Jackson, “Mortality benefits of influenza vaccination in elderly people: an ongoing controversy,” Lancet Infectious Diseases, vol. 7, no. 10, pp. 658–666, 2007.
[17]
J. C. Nelson, M. L. Jackson, N. S. Weiss, and L. A. Jackson, “New strategies are needed to improve the accuracy of influenza vaccine effectiveness estimates among seniors,” Journal of Clinical Epidemiology, vol. 62, no. 7, pp. 687–694, 2009.
[18]
T. M. Govaert, C. T. Thijs, N. Masurel, M. J. Sprenger, G. J. Dinant, and J. A. Knottnerus, “The efficacy of influenza vaccination in elderly individuals: a randomized double-blind placebo-controlled trial,” Journal of the American Medical Association, vol. 272, no. 21, pp. 1661–1665, 1994.
[19]
V. Parodi, D. De Florentiis, M. Martini, and F. Ansaldi, “Inactivated influenza vaccines: recent progress and implication for the elderly,” Drugs & Aging, vol. 28, no. 2, pp. 93–106, 2011.
[20]
T. Vesikari, M. Knuf, P. Wutzler, et al., “Oil-in-water emulsion adjuvant with influenza vaccine in young children,” The New England Journal of Medicine, vol. 365, no. 15, pp. 1406–1416, 2011.
[21]
T. Jefferson, A. Rivetti, A. Harnden, C. Di Pietrantonj, and V. Demicheli, “Vaccines for preventing influenza in healthy children,” Cochrane Database of Systematic Reviews, vol. 16, no. 2, article CD004879, 2008.
[22]
J. Rhorer, C. S. Ambrose, S. Dickinson et al., “Efficacy of live attenuated influenza vaccine in children: a meta-analysis of nine randomized clinical trials,” Vaccine, vol. 27, no. 7, pp. 1101–1110, 2009.
[23]
R. B. Belshe, K. M. Edwards, T. Vesikari, et al., “Live attenuated versus inactivated influenza vaccine in infants and young children,” The New England Journal of Medicine, vol. 356, no. 7, pp. 685–696, 2007.
[24]
T. Vesikari, N. Groth, A. Karvonen, A. Borkowski, and M. Pellegrini, “MF59-adjuvanted influenza vaccine (FLUAD) in children: safety and immunogenicity following a second year seasonal vaccination,” Vaccine, vol. 27, no. 45, pp. 6291–6295, 2009.
[25]
T. Vesikari, M. Pellegrini, A. Karvonen et al., “Enhanced immunogenicity of seasonal influenza vaccines in young children using MF59 adjuvant,” Pediatric Infectious Disease Journal, vol. 28, no. 7, pp. 563–571, 2009.
[26]
D. Frasca, A. Diaz, M. Romero, A. M. Landin, and B. B. Blomberg, “Age effects on B cells and humoral immunity in humans,” Ageing Research Reviews, vol. 10, no. 3, pp. 330–335, 2011.
[27]
S. Govind, A. Lapenna, P. O. Lang, and R. Aspinall, “Immunotherapy of immunosenescence: who, how and when?” Open Longevity Science. In press.
[28]
P. O. Lang, S. Govind, J. P. Michel, R. Aspinall, and W. A. Mitchell, “Immunosenescence: implications for vaccination programmes in adults,” Maturitas, vol. 68, no. 4, pp. 322–330, 2011.
[29]
J. E. McElhaney, “Influenza vaccine responses in older adults,” Ageing Research Reviews, vol. 10, no. 3, pp. 379–388, 2011.
[30]
R. B. Effros, “Role of T lymphocyte replicative senescence in vaccine efficacy,” Vaccine, vol. 25, no. 4, pp. 599–604, 2007.
[31]
I. A. de Bruijn, J. Nauta, L. Gerez, and A. M. Palache, “The virosomal influenza vaccine Invivac: immunogenicity and tolerability compared to an adjuvanted influenza vaccine (Fluad) in elderly subjects,” Vaccine, vol. 24, no. 44–46, pp. 6629–6631, 2006.
[32]
I. de Bruijn, I. Meyer, L. Gerez, J. Nauta, K. Giezeman, and B. Palache, “Antibody induction by virosomal, MF59-adjuvanted, or conventional influenza vaccines in the elderly,” Vaccine, vol. 26, no. 1, pp. 119–127, 2007.
[33]
P. O. Lang and R. Aspinall, “Immunosenescence and herd immunity: with an ever increasing aging population do we need to rethink vaccine schedules?” Expert Review of Vaccines, vol. 11, pp. 167–176, 2012.
[34]
R. B. Effros, M. Dagarag, C. Spaulding, and J. Man, “The role of CD8+ T-cell replicative senescence in human aging,” Immunological Reviews, vol. 205, pp. 147–157, 2005.
[35]
Centers for Disease Control and Prevention, “Impact of vaccines universally recommended for children—United States, 1990–1998,” Morbidity and Mortality Weekly Report, vol. 48, no. 12, pp. 243–248, 1999.
[36]
J. P. Michel, P. O. Lang, and J. P. Baeyens, “Flu vaccination policy in old adults: need for harmonization of national public health recommendations throughout Europe,” Vaccine, vol. 27, no. 2, pp. 182–183, 2009.
[37]
J. P. Michel, M. Gusmano, P. R. Blank, and I. Philp, “Vaccination and healthy ageing: how to make life-course vaccination a successful public health strategy,” European Geriatric Medicine, vol. 1, no. 3, pp. 155–165, 2010.
[38]
J. P. Baeyens, P. O. Lang, and J. P. Michel, “Willingness to vaccinate and to be vaccinated in adults,” Aging, vol. 21, no. 3, pp. 244–249, 2009.
[39]
G. A. Poland, R. M. Jacobson, and I. G. Ovsyannikova, “Trends affecting the future of vaccine development and delivery: the role of demographics, regulatory science, the anti-vaccine movement, and vaccinomics,” Vaccine, vol. 27, no. 25-26, pp. 3240–3244, 2009.
[40]
G. A. Poland and R. M. Jacobson, “The age-old struggle against the antivaccinationists,” The New England Journal of Medicine, vol. 364, no. 2, pp. 97–99, 2011.
[41]
A. E. Fiore, D. K. Shay, K. Broder et al., “Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008,” Morbidity and Mortality Weekly Report, vol. 57, no. 7, pp. 1–60, 2008.
[42]
T. Heikkinen, R. Booy, M. Campins et al., “Should healthy children be vaccinated against influenza? A consensus report of the Summits of Independent European Vaccination Experts,” European Journal of Pediatrics, vol. 165, no. 4, pp. 223–228, 2006.
[43]
J. P. Michel and P. O. Lang, “promoting life course vaccination,” Rejuvenation Research, vol. 14, no. 1, pp. 75–81, 2011.
[44]
T. A. Reichert, N. Sugaya, D. S. Fedson, W. P. Glezen, L. Simonsen, and M. Tashiro, “The japanese experience with vaccinating schoolchildren against influenza,” The New England Journal of Medicine, vol. 344, no. 12, pp. 889–896, 2001.
[45]
R. M. Anderson and R. M. May, “Immunisation and herd immunity,” The Lancet, vol. 335, no. 8690, pp. 641–645, 1990.
[46]
T. J. John and R. Samuel, “Herd immunity and herd effect: new insights and definitions,” European Journal of Epidemiology, vol. 16, no. 7, pp. 601–606, 2000.
[47]
Centers for Disease Control and Prevention, “Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008,” Morbidity and Mortality Weekly Report, vol. 57, no. 7, pp. 1–60, 2008.
[48]
W. R. Dowdle, J. D. Millar, L. B. Schonberger, F. A. Ennis, and J. R. LaMontagne, “Influenza immunization policies and practices in Japan,” Journal of Infectious Diseases, vol. 141, no. 2, pp. 258–264, 1980.
[49]
Y. Hirota, D. S. Fedson, and M. Kaji, “Japan lagging in influenza jabs,” Nature, vol. 380, no. 6569, p. 18, 1996.
[50]
N. Sugaya and Y. Takeuchi, “Mass vaccination of schoolchildren against influenza and its impact on the influenza-associated mortality rate among children in Japan,” Clinical Infectious Diseases, vol. 41, no. 7, pp. 939–947, 2005.
[51]
M. Takahashi and M. Nagai, “Estimation of excess mortality associated with influenza epidemics specific for sex, age and cause of death in Japan during 1987–2005,” Nippon Eiseigaku Zasshi, vol. 63, no. 1, pp. 5–19, 2008.
[52]
A. Cliff and P. Haggett, “Time, travel and infection,” British Medical Bulletin, vol. 69, pp. 87–99, 2004.
[53]
G. A. Poland, I. G. Ovsyannikova, and R. M. Jacobson, “Application of pharmacogenomics to vaccines,” Pharmacogenomics, vol. 10, no. 5, pp. 837–852, 2009.
[54]
A. Sette and R. Rappuoli, “Reverse vaccinology: developing vaccines in the era of genomics,” Immunity, vol. 33, no. 4, pp. 530–541, 2010.
[55]
United Nations (UN), “World Population Ageing: 1950–2050,” November 2011, http://www.un.org/esa/population/publications/worldageing19502050/.
[56]
J. Oeppen and J. W. Vaupel, “Demography. Broken limits to life expectancy,” Science, vol. 296, no. 5570, pp. 1029–1031, 2002.
[57]
T. Fulop, A. Larbi, J. M. Witkowski et al., “Aging, frailty and age-related diseases,” Biogerontology, vol. 11, no. 5, pp. 547–563, 2010.
[58]
P. O. Lang, W. A. Mitchell, A. Lapenna, D. Pitts, and R. Aspinall, “Immunological pathogenesis of main age-related diseases and frailty: role of immunosenescence,” European Geriatric Medicine, vol. 1, no. 2, pp. 112–121, 2010.
[59]
C. Franceschi, M. Capri, D. Monti et al., “Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans,” Mechanisms of Ageing and Development, vol. 128, no. 1, pp. 92–105, 2007.
[60]
P. O. Lang, “Adverse effects of the herd immunity or when childhood vaccination becomes deleterious for the epidemiology of infectious diseases in adults,” Geriatr Psychol Neuropsychiatr Vieil, vol. 9, no. 1, pp. 11–19, 2011.
[61]
P. R. Blank, M. Schwenkglenks, and T. D. Szucs, “Vaccination coverage rates in eleven European countries during two consecutive influenza seasons,” Journal of Infectious Diseases, vol. 58, no. 6, pp. 446–458, 2009.
[62]
B. Michiels, F. Govearts, R. Remmen, E. Vermeire, and S. Coenen, “A systematic review of the evidence on the effectiveness and risks of inactivated influenza vaccines in different target groups,” Vaccine, vol. 29, no. 49, pp. 9159–9170, 2011.
[63]
A. Nicoll and S. Tsolova, “Guidance priority risk groups for influenza vaccination. Stockholm: ECDC;,” 2008, http://ecdc.europa.eu/en/publications/Publications/0808_GUI_Priority_Risk_Groups_for_Influenza_Vaccination.pdf.
[64]
A. E. Fiore, T. M. Uyeki, K. Broder et al., “Prevention and control of influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2010,” Morbidity and Mortality Weekly Report, vol. 59, no. 8, pp. 1–62, 2010.
[65]
T. Jefferson, C. Di Pietrantonj, A. Rivetti, G. A. Bawazeer, L. A. Al-Ansary, and E. Ferroni, “Vaccines for preventing influenza in healthy adults,” Cochrane Database of Systematic Reviews (Online), vol. 7, article CD001269, 2010.
[66]
R. E. Thomas, T. Jefferson, and T. J. Lasserson, “Influenza vaccination for healthcare workers who work with the elderly,” Cochrane Database of Systematic Reviews (Online), vol. 2, article CD005187, 2010.
[67]
R. E. Thomas, T. Jefferson, and T. J. Lasserson, “Influenza vaccination for healthcare workers who work with the elderly: systematic review,” Vaccine, vol. 29, no. 2, pp. 344–356, 2010.
