Implicações da imunossenescência na vacinação de idosos

Malafaia, Guilherme

doi:10.1590/1809-9823.2008.110311

Resumo

A prevalência de indivíduos idosos em relação aos indivíduos jovens compreende um quadro comum na população mundial. Estima-se que, em 2050, cerca de 22% da população mundial será constituída por indivíduos idosos. No Brasil, o número de idosos (≥ 60 anos de idade) passou de 3 milhões em 1960 para 7 milhões em 1975 e 14 milhões em 2002 (um aumento de 500% em 40 anos), e estima-se que alcançará 32 milhões em 2020. Este fenômeno se deve ao advento de drogas antibacterianas, a vacinações em larga escala e a outros avanços no tratamento médico. Contudo, a eficácia de uma vacina depende, sobretudo, da habilidade dos indivíduos para exibir uma resposta imune adequada. Assim, esta revisão apresenta os principais efeitos da imunossenescência na resposta imune a uma vacina. Além disto, discute algumas estratégias que aumentam os níveis de proteção das imunizações neste grupo etário. A compreensão dos fatores envolvidos na geração de uma resposta imunológica durante a senescência e a introdução de estratégias que melhoram a eficácia de vacinas nos indivíduos idosos reduz a incidência e a severidade de doenças infecciosas, tendo forte impacto na qualidade de vida destes indivíduos.

Palavras-chave:
Envelhecimento; Sistema Imune; Imunoterapia ativa; Imunização; Adjuvantes imunológicos; Doenças transmissíveis; Comportamento de redução do risco; Incidência; Qualidade de vida; Brasil

Abstract

The increase of the elderly population is a worldwide common phenomenon. According to some projections, in the year 2050 older people will be about 22% of the world population. In Brazil the number of elderly (≥ 60 years of age) increased from 3 million in 1960, and to 7 million by 1975 and 14 million by 2002 (an increase of 500% in just forty years); according to estimates, it will reach 32 million by 2020. This phenomenon is due to advent of antibacterial drugs, large-scale vaccinations and other advances of medical treatment. However, the vaccine efficacy depends on the ability of individuals to exhibit an adequate immune response. This review presents the main effects of immunosenescence in immune response to a vaccine. Furthermore, it discusses strategies that may counteract age-related defects in immune responses to vaccination. The understanding of how immunological memory is affected by ageing, and the introduction of strategies to ameliorate vaccine efficacy in the elderly, might reduce the incidence and the severity of infectious disease and have a strong impact on the quality of life of elderly individuals.

Key words:
Ageing; Immune system; Immunotherapy active; Immunization; Adjuvants immunologic; Communicable diseases; Risk reduction behavior; Incidence; Quality of life; Brazil

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REFERÊNCIAS

¹
Wick G, et al. Diseases of Aging. Vaccine. 2000; 18:1567, 2000.
²
Fundação Instituto Brasileiro de Geografia e Estatística (IBGE). Diretoria de Pesquisas, Censos Demográficos. [citado em 2007 Set 21]. Disponível em: http://www.ibge.gov.br.
» http://www.ibge.gov.br.
³
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Berger R, Florent G, Just M. Decrease of the lymphoproliferative response to varicellazoster virus antigen in the aged. Infect Immun. 1981; 32:24-27.
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Nagami PH, Yoshikawa TT. Tuberculosis in the geriatric patient. J Am Geriatr Soc. 1983; 31:356-363.
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McVoy MA, Adler SP. Immunologic evidence for frequent age-related cytomegalovirus reactivation in seropositive immunocompetent individuals. J Infect Dis. 1989; 160:1-10.
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Gardner EM, et al. Age-related changes in the immune response to influenza vaccination in a racially diverse, healthy elderly population. Vaccine. 2006; 24:1609-1614.
⁸
Herndler-Brandstetter D, Cioca DP, Grubeck-Loebenstein B. Immunizations in the elderly: do they live up to their promise? Wien Med Wochenschr. 2006; 156:130-141.
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World Health Organization (WHO). Global Immunization. [citado em 2004]. Disponível em http://www.who.int/immunization_monitoring/data/.
» http://www.who.int/immunization_monitoring/data/
¹⁰
Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância Epidemiológica, Coordenação Geral do Programa Nacional de Imunizações. Informe técnico. Brasília: Ministério da Saúde; 2006.
¹¹
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¹²
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¹³
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¹⁴
Muszkat M, et al. Local IgA response following administration of a novel intranasal inactivated influenza virus vaccine in community residing elderly. Vaccine. 2000; 18:1696-1699.
¹⁵
Goodwin K, Viboud C, Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine. 2006; 24:1159-1169.
¹⁶
Cook JM, et al. Alterations in the human immune response to the hepatitis B vaccine among the elderly. Cell Immunol. 1987; 109:89-96.
¹⁷
Hainz U, et al. Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine. 2005, 23:3232-3235.
¹⁸
Haynes L, Swain SL. Whyaging Tcells fail: implications for vaccination. Immunity. 2006; 24:663-666.
¹⁹
Musher DM, et al. Natural and vaccine-related immunity to Streptococcus pneumoniae. J Infect Dis. 1986; 154:245-256.
²⁰
Aspinall R, Del Giudice G, Effros RB, Grubeck-Loebenstein B, Sambhara S. Challeneges for vaccination in the elderly. Immunity & Ageing. 2007; 4:9.
²¹
Malaguarnera L, et al. Immunosenescence: a review. Arch Gerontol Geriatr. 2001; 32:1-14.
²²
Beverley PC, Grubeck-Loebenstein B. Is immune senescence reversible? Vaccine. 2000; 18(16):1721-4.
²³
Douek DC, Koup RA. Evidence for thymic function in the elderly. Vaccine. 2000; 18(16):1638-41.
²⁴
Stacy S, Krolick KA, Infante AJ, Kraig E. Immunological memory and late onset autoimmunity. Mech Ageing Dev. 2002;123(8):975-85.
²⁵
Di Genova G, et al. Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific. Blood. 2006; 107:2806-2813.
²⁶
Novaes MRCG, Ito MK, Arruda SF, Rodrigues P, Lisboa AQ. Micronutrients supplementation during the senescence: implications for the immunological functions. Rev. Nutr. 2005; 18(3):367:376.
²⁷
Weksler ME, Goodhardt M. Do age-associated changes in "physiologic" autoantibodies contribute to infection, atherosclerosis, and Alzheimer's disease? Exp Geront. 2002; 37(8-9):971-9.
²⁸
Westendorp RG. What is healthy aging in the 21st century? Am J Clin Nutr. 2006; 83:404S-409S.
²⁹
Brewer JM. (How) do aluminium adjuvants work? Immunol Lett. 2006; 102:10-15.
³⁰
Sjolander A, Cox JC, Barr IG. ISCOMs: an adjuvant with multiple functions. J Leukoc Biol. 1998; 64:713-723.
³¹
Kovar M, et al. Direct stimulation of T cells by membrane vesicles from antigen-presenting cells. Proc Natl Acad Sci U S A. 2006; 103:11671-11676.
³²
Podda A, Del Giudice G. MF59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile. Expert Rev Vaccines. 2003; 2:197-203.
³³
Vandepapeliere P, et al. Potent enhancement of cellular and humoral immune responses against recombinant hepatitis B antigens using AS02A adjuvant in healthy adults. Vaccine. 2005; 23:2591-2601.
³⁴
Krieg AM. Therapeutic potential of Tolllike receptor 9 activation. Nat Rev Drug Discov. 2006; 5:471-484.
³⁵
Schellack C, et al. IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses. Vaccine. 2006; 24:5461-5472.
³⁶
Kutzler MA, et al. Coimmunization with na optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol. 2005; 175:112-123.
³⁷
Kovaiou DD, Herndler-Brandstetter D, Grubeck-Loebenstein B. Age-related changes in immunity: implications for vaccination in the elderly. Expert Rev. Mol. Med. 2007; 9:1-17.

Datas de Publicação

Publicação nesta coleção
Sep-Dec 2008

Histórico

Recebido
21 Jan 2008
Revisado
22 Jul 2008
Aceito
28 Ago 2008

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] ¹
Wick G, et al. Diseases of Aging. Vaccine. 2000; 18:1567, 2000.

[2] ²
Fundação Instituto Brasileiro de Geografia e Estatística (IBGE). Diretoria de Pesquisas, Censos Demográficos. [citado em 2007 Set 21]. Disponível em: http://www.ibge.gov.br.
» http://www.ibge.gov.br.

[3] ³
Castle SC. Clinical relevance of age-related immune dysfunction. Clin Infect Dis. 2000; 31:578-585.

[4] ⁴
Berger R, Florent G, Just M. Decrease of the lymphoproliferative response to varicellazoster virus antigen in the aged. Infect Immun. 1981; 32:24-27.

[5] ⁵
Nagami PH, Yoshikawa TT. Tuberculosis in the geriatric patient. J Am Geriatr Soc. 1983; 31:356-363.

[6] ⁶
McVoy MA, Adler SP. Immunologic evidence for frequent age-related cytomegalovirus reactivation in seropositive immunocompetent individuals. J Infect Dis. 1989; 160:1-10.

[7] ⁷
Gardner EM, et al. Age-related changes in the immune response to influenza vaccination in a racially diverse, healthy elderly population. Vaccine. 2006; 24:1609-1614.

[8] ⁸
Herndler-Brandstetter D, Cioca DP, Grubeck-Loebenstein B. Immunizations in the elderly: do they live up to their promise? Wien Med Wochenschr. 2006; 156:130-141.

[9] ⁹
World Health Organization (WHO). Global Immunization. [citado em 2004]. Disponível em http://www.who.int/immunization_monitoring/data/.
» http://www.who.int/immunization_monitoring/data/

[10] ¹⁰
Ministério da Saúde, Secretaria de Vigilância em Saúde, Departamento de Vigilância Epidemiológica, Coordenação Geral do Programa Nacional de Imunizações. Informe técnico. Brasília: Ministério da Saúde; 2006.

[11] ¹¹
Levine MM, Sztein MB. Vaccine development strategies for improving immunization: the role of modern immunology. Nat Immunol. 2004; 5:460-464.

[12] ¹²
Plotkin SA. Vaccines: past, present and future. Nat Med. 2005; 11:S5-11.

[13] ¹³
Lambert PH, Liu M, Siegrist CA. Can successful vaccines teach ushowto induce efficient protective immune responses? Nat Med. 2005; 11:S54-62.

[14] ¹⁴
Muszkat M, et al. Local IgA response following administration of a novel intranasal inactivated influenza virus vaccine in community residing elderly. Vaccine. 2000; 18:1696-1699.

[15] ¹⁵
Goodwin K, Viboud C, Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine. 2006; 24:1159-1169.

[16] ¹⁶
Cook JM, et al. Alterations in the human immune response to the hepatitis B vaccine among the elderly. Cell Immunol. 1987; 109:89-96.

[17] ¹⁷
Hainz U, et al. Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine. 2005, 23:3232-3235.

[18] ¹⁸
Haynes L, Swain SL. Whyaging Tcells fail: implications for vaccination. Immunity. 2006; 24:663-666.

[19] ¹⁹
Musher DM, et al. Natural and vaccine-related immunity to Streptococcus pneumoniae. J Infect Dis. 1986; 154:245-256.

[20] ²⁰
Aspinall R, Del Giudice G, Effros RB, Grubeck-Loebenstein B, Sambhara S. Challeneges for vaccination in the elderly. Immunity & Ageing. 2007; 4:9.

[21] ²¹
Malaguarnera L, et al. Immunosenescence: a review. Arch Gerontol Geriatr. 2001; 32:1-14.

[22] ²²
Beverley PC, Grubeck-Loebenstein B. Is immune senescence reversible? Vaccine. 2000; 18(16):1721-4.

[23] ²³
Douek DC, Koup RA. Evidence for thymic function in the elderly. Vaccine. 2000; 18(16):1638-41.

[24] ²⁴
Stacy S, Krolick KA, Infante AJ, Kraig E. Immunological memory and late onset autoimmunity. Mech Ageing Dev. 2002;123(8):975-85.

[25] ²⁵
Di Genova G, et al. Vaccination of human subjects expands both specific and bystander memory T cells but antibody production remains vaccine specific. Blood. 2006; 107:2806-2813.

[26] ²⁶
Novaes MRCG, Ito MK, Arruda SF, Rodrigues P, Lisboa AQ. Micronutrients supplementation during the senescence: implications for the immunological functions. Rev. Nutr. 2005; 18(3):367:376.

[27] ²⁷
Weksler ME, Goodhardt M. Do age-associated changes in "physiologic" autoantibodies contribute to infection, atherosclerosis, and Alzheimer's disease? Exp Geront. 2002; 37(8-9):971-9.

[28] ²⁸
Westendorp RG. What is healthy aging in the 21st century? Am J Clin Nutr. 2006; 83:404S-409S.

[29] ²⁹
Brewer JM. (How) do aluminium adjuvants work? Immunol Lett. 2006; 102:10-15.

[30] ³⁰
Sjolander A, Cox JC, Barr IG. ISCOMs: an adjuvant with multiple functions. J Leukoc Biol. 1998; 64:713-723.

[31] ³¹
Kovar M, et al. Direct stimulation of T cells by membrane vesicles from antigen-presenting cells. Proc Natl Acad Sci U S A. 2006; 103:11671-11676.

[32] ³²
Podda A, Del Giudice G. MF59-adjuvanted vaccines: increased immunogenicity with an optimal safety profile. Expert Rev Vaccines. 2003; 2:197-203.

[33] ³³
Vandepapeliere P, et al. Potent enhancement of cellular and humoral immune responses against recombinant hepatitis B antigens using AS02A adjuvant in healthy adults. Vaccine. 2005; 23:2591-2601.

[34] ³⁴
Krieg AM. Therapeutic potential of Tolllike receptor 9 activation. Nat Rev Drug Discov. 2006; 5:471-484.

[35] ³⁵
Schellack C, et al. IC31, a novel adjuvant signaling via TLR9, induces potent cellular and humoral immune responses. Vaccine. 2006; 24:5461-5472.

[36] ³⁶
Kutzler MA, et al. Coimmunization with na optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help. J Immunol. 2005; 175:112-123.

[37] ³⁷
Kovaiou DD, Herndler-Brandstetter D, Grubeck-Loebenstein B. Age-related changes in immunity: implications for vaccination in the elderly. Expert Rev. Mol. Med. 2007; 9:1-17.

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