Immunosenescence and vaccine failure in the elderly: Strategies for improving response

Immunology Letters

Volumn 162, Issue 1, 2014, Pages 346-353

  Boraschi, Diana ^a   Italiani, Paola ^a,b  

^a INSTITUTE OF PROTEIN BIOCHEMISTRY   (Italy)

^b CNR   (Italy)

Author keywords

Elderly; Immunosenescence; Vaccination

Indexed keywords

VACCINE;

AGE; AGED; AGING; HUMAN; IMMUNITY; IMMUNOLOGY; PHYSIOLOGY; PROCEDURES; VACCINATION; VERY ELDERLY;

AGE FACTORS; AGED; AGED, 80 AND OVER; AGING; HUMANS; IMMUNITY; VACCINATION; VACCINES;

EID: 84914159191     PISSN: 01652478     EISSN: 18790542     Source Type: Journal    
DOI: 10.1016/j.imlet.2014.06.006     Document Type: Article

References (125)

1. United Nations, Department of Economic and Social Affairs, Population Division (2002) World population ageing 1950-2050 2002, United Nations Publishing, New York, [accessed 19.05.09]. http://www.un.org/esa/population/publications/worldageing19502050/.
2. Crimmins E.M., Finch C.E. Infection, inflammation, height, and longevity. Proc Natl Acad Sci USA 2006, 103:498-503.
3. Haley P.J. Species differences in the structure and function of the immune system. Toxicology 2003, 188:49-71.
4. Mestas J., Hughes C.C.W. Of mice and not men: differences between mouse and human immunology. J Immunol 2004, 172:2731-2738.
5. Goronzy J.J., Weyand C.M. Understanding immunosenescence to improve responses to vaccines. Nat Immunol 2013, 14:428-436.
6. Davis M.M. A Prescription for human immunology. Immunity 2008, 29:835-838.
7. Lelic A., Verschoor C.P., Ventresca M., Parsons R., Evelegh C., Bowdish D., et al. The polyfunctionality of human memory CD8+ T cells elicited by acute and chronic virus infections is not influenced byage. PLoS Pathog 2012, 8:e1003076.
8. Olivieri F., Rippo M.R., Prattichizzo F., Babini L., Graciotti L., Recchioni R., et al. Toll like receptor signalingin "inflammaging": microRNA as new players. Immun Ageing 2013, 10:11.
9. Dewan S.K., Zheng S.B., Xia S.J., Bill K. Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Clin Med J 2012, 125:3325-3331.
10. Boraschi D., Aguado M.T., Dutel C., Goronzy J., Louis J., Grubeck-Loebenstein B., et al. The gracefully aging immune system. Sci Trans Med 2013, 5:185ps8.
11. Gavazzi G., Krause K.H. Ageing and infection. Lancet Infect Dis 2002, 2:659-666.
12. Wagner E.H., Groves T. Care for chronic diseases. Br Med J 2002, 325:913-914.
13. Jenny N.S. Inflammation in aging: cause, effect, or both?. Discov Med 2012, 13:451-460.
14. Frasca D., Blomberg B.B. Aging affects human cell responses. J Clin Immunol 2011, 31:430-435.
15. Arnold C.R., Wolf J., Brunner S., Herndler-Brandstetter D., Grubeck-Loebenstein B. Gain and loss of T cell subsets in old age - age related reshaping of the T cell repertoire. J Clin Immunol 2011, 31:137-146.
16. Su D.-M., Aw D., Palmer D.B. Immunosenescence: a product of the environment?. Curr Opin Immunol 2013, 25:496-503.
17. Tezil T., Basaga H. Modulation of cell death in age-related diseases. Curr Pharm Des 2013, 20. [Epub ahead of print].
18. Wang C.H., Wu S.B., Wu Y.T., Wei Y.H. Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging. Exp Biol Med (Maywood) 2013, 238:450-460.
19. Lesourd B. Nutritional factors and immunological ageing. Proc Nutr Soc 2006, 65:319-325.
20. Flicker L., McCaul K.A., Hankey G.J., Jamrozik K., Brown W.J., Byles J.E., et al. Body mass index and survival in men and women aged 70 to 75. J Am Geriatr Soc 2010, 58:234-241.
21. Kelley K.W., Weigent D.A., Kooijman R. Protein hormones and immunity. Brain Behav Immun 2007, 21:384-392.
22. Fulop T., Larbi A., Witkowski J.M., McElhaney J., Loeb M., Mitnitski A., et al. Aging, frailty and age-related diseases. Biogerontology 2010, 11:547-563.
23. Moreno G., Mangione C.M. Management of cardiovascular disease risk factors in older adults with type 2 diabetes mellitus: 2002-2012 literature review. Am Geriatr Soc 2013, 61:2027-2037.
24. Franceschi C. Inflammaging as a major characteristic of old people: can it be prevented or cured?. Nutr Rev 2007, 65:S173-S176.
25. Panda A., Qian F., Mohanty S., van Duin D., Newman F.K., Zhang L., et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol 2010, 184:2518-2527.
26. Nikolich-Zugich J., Rudd B.D. Immune memory and aging: an infinite or finite resource?. Curr Opin Immunol 2010, 22:535-540.
27. Johnson S.A., Cambier J.C. Ageing, autoimmunity and arthritis: senescence of the B cell compartment. Implications for humoral immunity. Arthritis Res Ther 2004, 6:131-139.
28. Gibson K.L., Wu Y.C., Barnett Y., Duggan O., Vaughan R., Kondeatis E., et al. B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell 2009, 8:18-25.
29. Weinberger B., Herndler-Brandstetter D., Schwanninger A., Weiskopf D., Grubeck-Loebenstein B. Biology of the immune response to vaccines in elderly persons. Clin Infect Dis 2008, 46:1078-1084.
30. Van Zant G., Liang Y. Concise review: hematopoietic stem cell aging, lifespan, and transplantation. Stem Cells Transl Med 2012, 1:651-657.
31. Beerman I., Maloney W.J., Weissmann I.L., Rossi D.J. Stem cells and the aging hematopoietic system. Curr Opin Immunol 2010, 22:500-506.
32. Tollervey J.R., Lunyak V.V. Epigenetics: judge, jury and executioner of stem cell fate. Epigenetics 2012, 7:823-840.
33. Tumpel S., Rudolph K.L. The role of telomere shortening in somatic stem cells and tissue aging: lessons from telomerase model systems. Ann NY Acad Sci 2012, 1266:28-39.
34. Sun L., Brown R., Chen S., Zhuge Q., Su D.M. Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus. Aging (Albany NY) 2012, 4:606-619.
35. Verschoor C.P., Johnstone J., Millar J., Dorrington M.G., Habibagahi M., Lelic A., et al. Blood CD33(+) HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol 2013, 93:633-637.
36. Jeisy-Scott V., Davis W.G., Patel J.R., Bowzard J.B., Shieh W.J., Zaki S.R., et al. Increased MDSC accumulation and Th2 biased response to influenza A virus infection in the absence of TLR7 in mice. PLoS One 2011, 6(9):e25242.
37. Wong C.P., Magnusson K.R., Ho E. Aging is associated with altered dendritic cells subset distribution and impaired proinflammatory cytokine production. Exp Gerontol 2010, 45:163-169.
38. Li G., Smithey M.J., Rudd B.D., Nikolich-Zugich J. Age-associated alterations in CD8 alpha+ dendritic cells impair CD8 T cell expansion in response to an intracellular bacterium. Aging Cell 2012, 11:968-977.
39. Jing Y., Shaheen E., Drake R., Chen N., Gravenstein S., Deng Y. Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Human Immunol 2009, 70:777-861.
40. Pereira L.F., DeSouza A.P., Borges T.J., Bonorino C. Impaired in vivo CD4+ T cell expansion and differentiation in aged mice is not solely due to T cell defects: decreased stimulation by aged dendritic cells. Mech Ageing Dev 2011, 132:187-194.
41. Grolleau-Julius A., Harning E.K., Abernathy L.M., Yung R.L. Impaired dendritic cell function in aging leads to defective anti-tumor immunity. Cancer Res 2008, 68:6341-6349.
42. Paula C., Motta A., Schmitz C., Nunes C.P., Souza A.P., Bonorino C. Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design. Biogerontology 2009, 10:13-25.
43. Zhao J., Legge K., Perlman S. Age-related increases in PGD(2) expression impair respiratory DC migration, resulting in diminished T cell responses upon respiratory virus infection in mice. J Clin Invest 2011, 121:4921-4930.
44. Tan S.Y., Cavanagh L.L., D'advigor W., Shackel N., De St Groth B., Weninger W. Phenotype and functions of conventional dendritic cells are not compromised in aged mice. Immunol Cell Biol 2012, 90:722-732.
45. Agrawal A., Sridharan A., Prakash S., Agrawal H. Dendritic cells and aging: consequences for autoimmunity. Expert Rev Clin Immunol 2012, 8:73-80.
46. Shaw A.C., Panda A., Joshi S.R., Qian F., Allore H.G., Montgomery R.R. Dysregulation of human Toll-like receptor function in aging. Ageing Res Rev 2011, 10:346-353.
47. Gomez C.R., Boehmer E.D., Kovacs E.J. The aging innate immune system. Curr Opin Immunol 2005, 17:457-462.
48. Dunston C.R., Griffiths H.R. The effect of ageing on macrophage Toll-like receptor mediated responses in the fight against pathogens. Clin Exp Immunol 2010, 161:407-416.
49. Goral J., Kovacs E.J. In vivo ethanol exposure down-regulates TLR2-, TLR4-, and TLR9-mediated macrophage inflammatory response by limiting p38 and ERK1/2 activation. J Immunol 2005, 174:456-463.
50. Nguyen C.T., Kim S.Y., Kim M.S., Lee S.E., Rhee J.H. Intranasal immunization with recombinant PspA fused with a flagellin enhances crossprotective immunity against Streptococcus pneumoniae infection in mice. Vaccine 2010, 29:5731-5739.
51. Solana R., Tarazona R., Gayoso I., Lesur O., Dupuis G., Fulop T. Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol 2012, 24:331-341.
52. Shaw A.C., Joshi S., Greenwood H., Panda A., Lord J.M. Aging of the innate immune system. Curr Opin Immunol 2010, 22:507-513.
53. Meier J., Sturm A. The intestinal epithelial barrier: does it become impaired with age?. Dig Dis 2009, 27:240-245.
54. McElhaney J.E., Zhou X., Talbot H.K., Soethout E., Bleackley R.C., Granville D.J., et al. The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty area challenge for the development of more effective influenza vaccines. Vaccine 2012, 30:2060-2067.
55. Harper J.M., Wilkinson J.E., Miller R.A. Macrophage migration inhibitory factor-knockout mice are long lived and respond to caloric restriction. FASEB J 2010, 24:2436-2442.
56. Franceschi C., Capri M., Monti D., Giunta S., Olivieri F., Sevini F., et al. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 2007, 128:92-105.
57. Grubeck-Loebenstein B. Changes in the aging immune system. Biologicals 1997, 25:205-208.
58. Tamir A., Eisenbraun M.D., Garcia G.G., Miller R.A. Age-dependent alterations in the assembly of signal transduction complexes at the site of T cell/APC interaction. J Immunol 2000, 165:1243-1251.
59. Effros R.B. Role of T lymphocyte replicative senescence in vaccine efficacy. Vaccine 2007, 25:599-604.
60. Czesnikiewicz-Guzik M., Lee W.-W., Cui D., Hiruma Y., Lamar D., Yang Z.-Z., et al. T cell subset-specific susceptibility to aging. Clin Immunol 2008, 127:107-125.
61. Lelic A., Verschoor C.P., Ventresca M., Parsons R., Evelegh C., Bowdish D., et al. The polyfunctionality of human memory CD8+ T cells elicited by acute and chronic virus infections is not influenced by age. PLoS Pathog 2012, 8:e1003076.
62. Yu M., Li G., Lee W.-W., Yuan M., Cui D., Weyand C., et al. Signal inhibition by the dual-specific phosphatase 4 impairs T cell-dependent B-cell responses with age. Proc Natl Acad Sci USA 2012, 109:88.
63. Blomberg B.B., Frasca D. Quantity not quality of antibody response decreased in the elderly. J Clin Invest 2011, 121:2981-2983.
64. Sasaki S., Sullivan M., Narvaez C.F., Holmes T.H., Furman D., Zheng N.Y., et al. Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. J Clin Invest 2011, 121:3109-3119.
65. Cadeddu C., DeWaure C., Gualano M.R., DiNardo F., Ricciardi W. 23 Valent pneumococcal polysaccharide vaccine (PPV23) for the prevention of invasive pneumococcal diseases (IPDs) in the elderly: is it really effective?. J Prev Med Hyg 2012, 53:101-103.
66. Ongradi J., Kovesdi V. Numerical alterations of ageing B lymphocyte subsets. Acta Physiol Hung 2011, 98:99-104.
67. Castelo-Branco C., Soveral I. The immune system and aging: a review. Gynecol Endocrinol 2014, 30:16-22.
68. Panda A., Arjona A., Sapey E., Bai F., Fikrig E., Montgomery R.R., et al. Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 2009, 30:325-333.
69. Montecino-Rodriguez E., Berent-Maoz B., Dorshkind K. Causes, consequences, and reversal of immune system aging. J Clin Invest 2013, 123:958-965.
70. Schmader K. Herpes zoster in older adults. Clin Infect Dis 2001, 32:1481-1486.
71. CDC Estimates of deaths associated with seasonal influenza-United States, 1976-2007. MMWR Morb Mortal Wkly Rep 2010, 59:1057-1062.
72. Edwards M.S., Baker C.J. Group B streptococcal infections in elderly adults. Clin Infect Dis 2005, 41:839-847.
73. ®): results of two randomized trials. Vaccine 2012, 30:1721-1728.
74. Nichol K.L., Nordin J.D., Nelson D.B., Mullooly J.P., Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med 2007, 357:1373-1381.
75. Levin M.J. Immune senescence and vaccines to prevent herpes zoster in older persons. Curr Opin Immunol 2012, 24:494-500.
76. Sasaki S., He X.S., Holmes T.H., Dekker C.L., Kemble G.W., Arvin A.M., et al. Influence of prior influenza vaccination on antibody and B-cell responses. PLoS One 2008, 3:e2975.
77. Rappuoli R., Mandl C.W., Black S., De Gregorio E. Vaccines for the twenty-first century society. Nat Rev Immunol 2011, 11:865-872.
78. Potter C.W., Oxford J.S. Determinants of immunity to influenza in man. Br Med Bull 1979, 35:69-75.
79. Osterholm M.T., Kelley N.S., Sommer A., Belongia E.A. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis 2012, 12:36-44.
80. Goodwin K., Viboud C., Simonsen L. Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 2006, 24:1159-1169.
81. El Shikh M.E., ElSayed R.M., Sukumar S., Szakal A.K., Tew J.G. Activation of B cells by antigens on follicular dendritic cells. Trends Immunol 2010, 31:205-211.
82. Keitel W.A., Cate T.R., Atmar R.L., Turner C.S., Nino D., Dukes C.M., et al. Increasing doses of purified influenza virus hemagglutinin and subvirion vaccines enhance antibody responses in the elderly. Clin Diagn Lab Immunol 1996, 3:507-510.
83. Keitel W.A., Couch R.B., Cate T.R., Hess K.R., Baxter B., Quarles J.M., et al. High doses of purified influenza A virus heagglutinin significantly augment serum and nasal secretion antibody responses in healthy young adults. J Clin Microbiol 1994, 32:2468-2473.
84. DiazGranados C.A., Dunning A.J., Jordanov E., Landolfi V., Denis M., Talbot H.K. High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: safety, immunogenicity and relative efficacy during the 2009-2010 season. Vaccine 2013, 31:861-866.
85. Chen W.H., Cross A.S., Edelman R., Sztein M.B., Blackwelder W.C., Pasetti M.F. Antibody and Th1-type cell-mediated immune responses in elderly and young adults immunized with the standard or a high dose influenza vaccine. Vaccine 2011, 29:2865-2873.
86. Pfister G., Weiskopf D., Lazuardi L., Kovaiou R.D., Cioca D.P., Keller M., et al. Naïve T cells in the elderly: are they still there?. Ann N Y Acad Sci 2006, 1067:152-157.
87. Kang I., Hong M.S., Nolasco H., Park S.H., Dan J.M., Choi J.Y., et al. Age-associated change in the frequency of memory CD4+ T cells impairs long term CD4+ T cell responses to influenza vaccine. J Immunol 2004, 173:673-681.
88. Hainz U., Jenewein B., Asch E., Pfeiffer K.P., Berger P., Grubeck-Loebenstein B. Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine 2005, 23:3232-3235.
89. Beyer W.E., Palache A.M., de Jong J.C., Osterhaus A.D. Cold-adapted live influenza vaccine versus inactivated vaccine: systemic vaccine reactions, local and systemic antibody response, and vaccine efficacy. A meta-analysis. Vaccine 2002, 20:1340-1353.
90. Rhorer J., Ambrose C.S., Dickinson S., Hamilton H., Oleka N.A., Malinoski F.J., et al. Efficacy of live attenuated influenza vaccine in children: a meta-analysis of nine randomized clinical trials. Vaccine 2009, 27:1101-1110.
91. Ambrose C.S., Wu X., Belshe R.B. The efficacy of live attenuated and inactivated influenza vaccines in children as a function of time postvaccination. Pediatr Infect Dis J 2010, 29:806-811.
92. Eick A.A., Wang Z., Hughes H., Ford S.M., Tobler S.K. Comparison of the trivalent live attenuated vs. inactivated influenza vaccines among U.S. military service members. Vaccine 2009, 27:3568-3575.
93. Wang Z., Tobler S., Roayaei J., Eick A. Live attenuated or inactivated influenza vaccines and medical encounters for respiratory illnesses among US military personnel. JAMA 2009, 301:945-953.
94. Kaml M., Weiskirchner I., Keller M., Luft T., Hoster E., Hasford J., et al. Booster vaccination in the elderly: their success depends on the vaccine type applied earlier in life as well as on pre-vaccination antibody titers. Vaccine 2006, 24:6808-6811.
95. Weinberger B., Schirmer M., Matteucci Gothe R., Siebert U., Fuchs D., Grubeck-Loebenstein B. Recall responses to tetanus and diphtheria vaccination are frequently insufficient in elderly persons. PLoS One 2013, 8:e82967.
96. Martin M., Weld L.H., Tsai T.F., Mootrey G.T., Chen R.T., Niu M., et al. Advanced age a risk factor for illness temporally associated with yellow fever vaccination. Emerg Infect Dis 2001, 7:945-951.
97. Weinberger B., Herndler-Brandstetter D., Schwanninger A., Weiskopf D., Grubeck-Loebenstein B. Biology of immune responses to vaccines in elderly persons. Clin Infect Dis 2008, 46:1078-1084.
98. Roos-Van Eijndhoven D.G., Cools H.J., Westendorp R.G., Ten Cate-Hoek A.J., Knook D.L., Remarque E.J. Randomized controlled trial of seroresponses to double dose and booster influenza vaccination in frail elderly subjects. J Med Virol 2001, 63(4):293-298.
99. Agius E., Lacy K., Vukmanovic-Stejic M., Jagger A., Papageorgiou A.P., Hall S., et al. Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+T cells during aging. J Exp Med 2009, 206:1929-1969.
100. Durando P., Iudici R., Alicino C., Alberti M., de F.D., Ansaldi F., et al. Adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine. Hum Vaccin 2011, 7(Suppl.):29-40.
101. Ansaldi F., Orsi A., de Florentiis D., Parodi V., Rappazzo E., Coppelli M., et al. Head-to-head comparison of an intradermal and a virosome influenza vaccine in patients over the age of 60: evaluation of immunogenicity, cross-protection, safety and tolerability. Hum Vaccin Immunother 2013, 9:591-598.
102. Holland D., Booy R., De L.F., Eizenberg P., McDonald J., Karrasch J., et al. Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly adults: a randomized controlled trial. J Infect Dis 2008, 198:650-658.
103. Patel S.M., Atmar R.L., El Sahly H.M., Guo K., Hill H., Keitel W.A. Direct comparison of an inactivated subvirion influenza A virus subtype H5N1 vaccine administered by the intradermal and intramuscular routes. J Infect Dis 2012, 206:1069-1077.
104. Marra F., Young F., Richardson K., Marra C.A. A meta-analysis of intradermal versus intramuscular influenza vaccines: immunogenicity and adverse events. Influenza Other Respir Viruses 2013, 7:584-603.
105. Tetsutani K., Ishii K.J. Adjuvants in influenza vaccines. Vaccine 2012, 30:7658-7661.
106. Podda A., Del Giudice G., O'Hagan D.T. MF59: a safe and potent adjuvant for human use. Immunopotentiators in modern medicines 2005, Elsevier Press, Amsterdam, [chapter 9]. V. Schijns, D.T. O'Hagan (Eds.).
107. O'Hagan D.T., Ott G.S., DeGregorio E., Seubert A. The mechanism of action of MF59 an innately attractive adjuvant formulation. Vaccine 2012, 30:4341-4348.
108. Cheong H.J., Song J.Y., Heo J.Y., Noh J.Y., Choi W.S., Park D.W., et al. Immunogenicity and safety of the influenza A/H1N1 2009 inactivated split-virus vaccine in young and older adults: MF59-adjuvanted vaccine versus non adjuvanted vaccine. Clin Vaccine Immunol 2011, 18:1358-1364.
109. Bihari I., Panczel G., Kovacs J., Beygo J., Fragapane E. Assessment of antigen-specific and cross-reactive antibody responses to an MF59-adjuvanted A/H5N1 prepandemic influenza vaccine in adult and elderly subjects. Clin Vaccine Immunol 2012, 19:1943-1948.
110. Mosca F., Tritto E., Muzzi A., Monaci E., Bagnoli F., Iavarone C., et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci U S A 2008, 105:10501-10506.
111. Mannino S., Villa M., Apolone G., Weiss N.S., Groth N., Aquino I., et al. Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy. Am J Epidemiol 2012, 176:527-533.
112. Baldo V., Baldovin T., Pellegrini M., Angiolelli G., Majori S., Floreani A., et al. Immunogenicity of three different influenza vaccines against homologous and heterologous strains in nursing home elderly residents. Clin Dev Immunol 2010, 2010. article id: 517198.
113. Sindoni D., La F.V., Squeri R., Cannavo G., Bacilieri S., Panatto D., et al. Comparison between a conventional subunit vaccine and the MF59-adjuvanted subunit influenza vaccine in the elderly: an evaluation of the safety, tolerability and immunogenicity. J Prev Med Hyg 2009, 50:121-126.
114. Duthie M.S., Windish H.P., Fox C.B., Reed S.G. Use of defined TLR ligands as adjuvants within human vaccines. Immunol Rev 2011, 239:178-196.
115. Steinhagen F., Kinjo T., Bode C., Klinman D.M. TLR-based immune adjuvants. Vaccine 2011, 29:3341-3355.
116. Huang H., Ostroff G.R., Lee C.K., Wang J.P., Specht C.A., Levitz S.M. Distinct patterns of dendritic cell cytokine release stimulated by fungal beta-glucans and Toll-like receptor agonists. Infect Immun 2009, 77:1774-1781.
117. DeFranco A.L., Rookhuizen D.C., Hou B. Contribution of Toll-like receptor signaling to germinal center antibody responses. Immunol Rev 2012, 247:64-72.
118. Behzad H., Huckriede A.L., Haynes L., Gentleman B., Coyle K., Wilschut J.C., et al. GLA-SE, a synthetic Toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults. J Infect Dis 2012, 205:466-473.
119. Taylor D.N., Treanor J.J., Strout C., Johnson C., Fitzgerald T., Kavita U., et al. Induction of a potent immune response in the elderly using the TLR-5 agonist, flagellin, with a recombinant hemagglutinin influenza-flagellin fusion vaccine (VAX125, STF2.HA1 SI). Vaccine 2011, 29:4897-4902.
120. Taylor D.N., Treanor J.J., Sheldon E.A., Johnson C., Umlauf S., Song L., et al. Development of VAX128, are combinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response. Vaccine 2012, 30:5761-5769.
121. McElhaney J.E., Xie D., Hager W.D., Barry M.B., Wang Y., Kleppinger A., et al. T cell responses are better correlates of vaccine protection in the elderly. J Immunol 2006, 176:6333-6339.
122. Berthoud T.K., Hamill M., Lillie P.J., Hwenda L., Collins K.A., Ewer K.J., et al. Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVA-NP+M1. Clin Infect Dis 2011, 52:1-7.
123. Doucet J.D., Forget M.A., Grange C., Rouxel R.N., Arbour N., von M.V., et al. Endogenously expressed matrix protein M1 and nucleoprotein of influenza A are efficiently presented by class I and class II major histocompatibility complexes. J Gen Virol 2011, 92:1162-1171.
124. Antrobus R.D., Lillie P.J., Berthoud T.K., Spencer A.J., McLaren J.E., Ladell K., et al. A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS One 2012, 7:e48322.
125. Kim T.H., Johnstone J., Loeb M. Vaccine herd effect. Scand J Infect Dis 2011, 43:683-689.