Immunosenescence and novel vaccination strategies for the elderly

Frontiers in Immunology

Volumn 4, Issue JUN, 2013, Pages

  Dorrington, Michael G ^a   Bowdish, Dawn M E ^a  

^a MCMASTER UNIVERSITY   (Canada)

Author keywords

Adjuvants; Elderly; Human; Immunosenescence; Influenza; Pneumonia; Vaccination; Vaccination strategies

Indexed keywords

ADJUVANT; ADJUVANT AS03; DIPHTHERIA PERTUSSIS TETANUS VACCINE; FLAGELLIN; GAMMA INTERFERON; IMMUNOGLOBULIN G; INFLUENZA VACCINE; INTERLEUKIN 2; INTERLEUKIN 6; MATRIX M; MATRIX PROTEIN; MIFAMURTIDE; NUCLEOPROTEIN; PNEUMOCOCCUS VACCINE; RECOMBINANT VACCINE; T LYMPHOCYTE RECEPTOR; TOLL LIKE RECEPTOR 5; TOLL LIKE RECEPTOR AGONIST; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VACCINE; VAX128;

AGED; AGING; ANTIGEN PRESENTATION; DIPHTHERIA; DRUG DOSE COMPARISON; DRUG DOSE INCREASE; DRUG MEGADOSE; HERD IMMUNITY; HUMAN; IMMUNOSENESCENCE; INFLUENZA; INNATE IMMUNITY; LOW DRUG DOSE; NONHUMAN; PERTUSSIS; REVIEW; SENESCENCE; STREPTOCOCCUS PNEUMONIA; STREPTOCOCCUS PNEUMONIAE; TETANUS; UNSPECIFIED SIDE EFFECT; VACCINATION;

EID: 84883706307     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2013.00171     Document Type: Review

References (83)

1. Alagappan, K., Rennie, W., Kwiatkowski, T., and Narang, V. (1997). Antibody protection to diphtheria in geriatric patients: need for ED compliance with immunization guidelines. Ann. Emerg. Med. 30, 455-458. doi:10.1016/S0196-0644(97)70004-0
2. Antrobus, R. D., Lillie, P. J., Berthoud, T. K., Spencer, A. J., McLaren, J. E., Ladell, K., et al. (2012). A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years. PLoS ONE 7, e48322. doi:10.1371/journal.pone.0048322
3. Arnold, C. R., Wolf, J., Brunner, S., Herndler-Brandstetter, D., and Grubeck-Loebenstein, B. (2011). Gain and loss of T cell subsets in old age-age-related reshaping of the T cell repertoire. J. Clin. Immunol. 31, 137-146. doi:10.1007/s10875-010-9499-x
4. Bates, J. T., Honko, A. N., Graff, A. H., Kock, N. D., and Mizel, S. B. (2008). Mucosal adjuvant activity of flagellin in aged mice. Mech. Ageing Dev. 129, 271-281. doi:10.1016/j.mad.2008.01.009
5. Blomberg, B. B., and Frasca, D. (2011). Quantity, not quality, of antibody response decreased in the elderly. J. Clin. Invest. 121, 2981-2983. doi:10.1172/JCI58406
6. Butler, J. C., Breiman, R. F., Campbell, J. F., Lipman, H. B., Broome, C. V., and Facklam, R. R. (1993). Pneumococcal polysaccharide vaccine efficacy. An evaluation of current recommendations. JAMA 270, 1826-1831. doi:10.1001/jama.270.15.1826
7. Cadeddu, C., De Waure, C., Gualano, M. R., Di Nardo, F., and Ricciardi, W. (2012). 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. 53, 101-103.
8. Canada, P. H. A. O. (ed.). (2012). Canadian Immunization Guide. Ottawa: P.H.A.O. Canada.
9. Chen, W. H., Kozlovsky, B. F., Effros, R. B., Grubeck-Loebenstein, B., Edelman, R., and Sztein, M. B. (2009). Vaccination in the elderly: an immunological perspective. Trends Immunol. 30, 351-359. doi:10.1016/j.it.2009.05.002
10. Cohen, S. A., Agree, E. M., Ahmed, S., and Naumova, E. N. (2011a). Grandparental caregiving, income inequality and respiratory infections in elderly US individuals. J. Epidemiol. Community Health 65, 246-253. doi:10.1136/jech.2009.093476
11. Cohen, S. A., Chui, K. K., and Naumova, E. N. (2011b). Influenza vaccination in young children reduces influenza-associated hospitalizations in older adults, 2002-2006. J. Am. Geriatr. Soc. 59, 327-332. doi:10.1111/j.1532-5415.2010.03271.x
12. Czajka, H., Unal, S., Ulusoy, S., Usluer, G., Strus, A., Sennaroglu, E., et al. (2012). A phase II, randomised clinical trial to demonstrate the non-inferiority of low-dose MF59-adjuvanted pre-pandemic A/H5N1 influenza vaccine in adult and elderly subjects. J. Prev. Med. Hyg. 53, 136-142.
13. Dear, K., Holden, J., Andrews, R., and Tatham, D. (2003). Vaccines for preventing pneumococcal infection in adults. Cochrane Database Syst. Rev. 4, CD000422. doi:10.1002/14651858.CD000422.pub3
14. Della Cioppa, G., Nicolay, U., Lindert, K., Leroux-Roels, G., Clement, F., Castellino, F., et al. (2012). Superior immunogenicity of seasonal influenza vaccines containing full dose of MF59 ((R)) adjuvant: results from a dose-finding clinical trial in older adults. Hum. Vaccin. Immunother. 8, 216-227. doi:10.4161/hv.18445
15. Dewan, S. K., Zheng, S. B., Xia, S. J., and Bill, K. (2012). Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Chin. Med. J. 125, 3325-3331.
16. DiazGranados, C. A., Dunning, A. J., Jordanov, E., Landolfi, V., Denis, M., and Talbot, H. K. (2013). High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: safety, immunogenicity and relative efficacy during the 2009-2010 season. Vaccine 31, 861-866. doi:10.1016/j.vaccine.2012.12.013
17. Duthie, M. S., Windish, H. P., Fox, C. B., and Reed, S. G. (2011). Use of defined TLR ligands as adjuvants within human vaccines. Immunol. Rev. 239, 178-196. doi:10.1111/j.1600-065X.2010.00978.x
18. Earn, D. J., He, D., Loeb, M. B., Fonseca, K., Lee, B. E., and Dushoff, J. (2012). Effects of school closure on incidence of pandemic influenza in Alberta, Canada. Ann. Intern. Med. 156, 173-181. doi:10.7326/0003-4819-156-3-201202070-00005
19. El Shikh, M. E., El Sayed, R. M., Sukumar, S., Szakal, A. K., and Tew, J. G. (2010). Activation of B cells by antigens on follicular dendritic cells. Trends Immunol. 31, 205-211. doi:10.1016/j.it.2010.03.002
20. Falsey, A. R., Treanor, J. J., Tornieporth, N., Capellan, J., and Gorse, G. J. (2009). Randomized, double-blind controlled phase 3 trial comparing the immunogenicity of high-dose and standard-dose influenza vaccine in adults 65 years of age and older. J. Infect. Dis. 200, 172-180. doi:10.1086/599790
21. Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., et al. (2007). Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev. 128, 92-105. doi:10.1016/j.mad.2006.11.016
22. Frasca, D., and Blomberg, B. B. (2011). Aging affects human B cell responses. J. Clin. Immunol. 31, 430-435. doi:10.1007/s10875-010-9501-7
23. Fujita, Y., and Taguchi, H. (2012). Overview and outlook of Toll-like receptor ligand-antigen conjugate vaccines. Ther. Deliv. 3, 749-760. doi:10.4155/tde.12.52
24. Fukase, H., Furuie, H., Yasuda, Y., Komatsu, R., Matsushita, K., Minami, T., et al. (2012). Assessment of the immunogenicity and safety of varying doses of an MF59(R)-adjuvanted cell culture-derived A/H1N1 pandemic influenza vaccine in Japanese paediatric, adult and elderly subjects. Vaccine 30, 5030-5037. doi:10.1016/j.vaccine.2012.03.053
25. Glezen, W. P. (1996). Emerging infections: pandemic influenza. Epidemiol. Rev. 18, 64-76. doi:10.1093/oxfordjournals.epirev.a017917
26. Grolleau-Julius, A., Harning, E. K., Abernathy, L. M., and Yung, R. L. (2008). Impaired dendritic cell function in aging leads to defective antitumor immunity. Cancer Res. 68, 6341-6349. doi:10.1158/0008-5472.CAN-07-5769
27. Gross, P. A., Hermogenes, A. W., Sacks, H. S., Lau, J., and Levandowski, R. A. (1995). The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann. Intern. Med. 123, 518-527. doi:10.7326/0003-4819-123-7-199510010-00008
28. Hainz, U., Jenewein, B., Asch, E., Pfeiffer, K. P., Berger, P., and Grubeck-Loebenstein, B. (2005). Insufficient protection for healthy elderly adults by tetanus and TBE vaccines. Vaccine 23, 3232-3235. doi:10.1016/j.vaccine.2005.01.085
29. Harper, J. M., Wilkinson, J. E., and Miller, R. A. (2010). Macrophage migration inhibitory factor-knockout mice are long lived and respond to caloric restriction. FASEB J. 24, 2436-2442. doi:10.1096/fj.09-152223
30. Hsu, H. E., Shutt, K. A., Moore, M. R., Beall, B. W., Bennett, N. M., Craig, A. S., et al. (2009). Effect of pneumococcal conjugate vaccine on pneumococcal meningitis. N. Engl. J. Med. 360, 244-256. doi:10.1056/NEJMoa0800836
31. Jefferson, T., Rivetti, D., Rivetti, A., Rudin, M., Di Pietrantonj, C., and Demicheli, V. (2005). Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review. Lancet 366, 1165-1174. doi:10.1016/S0140-6736(05)67339-4
32. Jenny, N. S. (2012). Inflammation in aging: cause, effect, or both? Discov. Med. 13, 451-460.
33. Johnstone, J., Eurich, D. T., Minhas, J. K., Marrie, T. J., and Majumdar, S. R. (2010). Impact of the pneumococcal vaccine on long-term morbidity and mortality of adults at high risk for pneumonia. Clin. Infect. Dis. 51, 15-22. doi:10.1086/653114
34. Jokinen, C., Heiskanen, L., Juvonen, H., Kallinen, S., Karkola, K., Korppi, M., et al. (1993). Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am. J. Epidemiol. 137, 977-988.
35. Kim, T. H., Johnstone, J., and Loeb, M. (2011). Vaccine herd effect. Scand. J. Infect. Dis. 43, 683-689.
36. Lelic, A., Verschoor, C. P., Ventresca, M., Parsons, R., Evelegh, C., Bowdish, D., et al. (2012). The polyfunctionality of human memory CD8+ T cells elicited by acute and chronic virus infections is not influenced by age. PLoS Pathog. 8, e1003076. doi:10.1371/journal.ppat.1003076
37. Li, G., Smithey, M. J., Rudd, B. D., and Nikolich-Zugich, J. (2012). Age-associated alterations in CD8alpha+ dendritic cells impair CD8 T-cell expansion in response to an intracellular bacterium. Aging Cell 11, 968-977. doi:10.1111/j.1474-9726.2012.00867.x
38. Lode, H., Schmoele-Thoma, B., Gruber, W., Ahlers, N., Fernsten, P., Baker, S., et al. (2011). Dose-ranging study of a single injection of pneumococcal conjugate vaccine (1 x, 2 x, or 4 x) in healthy subjects aged 70 years or older. Vaccine 29, 4940-4946. doi:10.1016/j
39. Loeb, M., Russell, M. L., Moss, L., Fonseca, K., Fox, J., Earn, D. J., et al. (2010). Effect of influenza vaccination of children on infection rates in Hutterite communities: a randomized trial. JAMA 303, 943-950. doi:10.1001/jama.2010.250
40. Magnusson, S. E., Reimer, J. M., Karlsson, K. H., Lilja, L., Bengtsson, K. L., and Stertman, L. (2013). Immune enhancing properties of the novel Matrix-M adjuvant leads to potentiated immune responses to an influenza vaccine in mice. Vaccine 31, 1725-1733. doi:10.1016/j.vaccine.2013.01.039
41. Mahbub, S., Deburghgraeve, C. R., and Kovacs, E. J. (2012). Advanced age impairs macrophage polarization. J. Interferon Cytokine Res. 32, 18-26. doi:10.1089/jir.2011.0058
42. Mannino, S., Villa, M., Apolone, G., Weiss, N. S., Groth, N., Aquino, I., et al. (2012). Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy. Am. J. Epidemiol. 176, 527-533. doi:10.1093/aje/kws313
43. Manzoli, L., Ioannidis, J. P., Flacco, M. E., De Vito, C., and Villari, P. (2012). Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly: a critical review and re-analysis of 15 meta-analyses. Hum. Vaccin. Immunother. 8, 851-862. doi:10.4161/hv.19917
44. Matsushita, M., Takeuchi, S., Kumagai, N., Uehara, Y., Matsushita, C., Arise, K., et al. (2012). Prevaccination antibody titers can estimate the immune response to influenza vaccine in a rural community-dwelling elderly population. Vaccine 30, 1101-1107. doi:10.1016/j.vaccine.2011.12.024
45. McElhaney, J. E., Beran, J., Devaster, J. M., Esen, M., Launay, O., Leroux-Roels, G., et al. (2013). AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial. Lancet Infect. Dis. 13, 485-496. doi:10.1016/S1473-3099(13)70046-X
46. McElhaney J. E., Xie, D., Hager, W. D., Barry, M. B., Wang, Y., Kleppinger, A., et al. (2006). T cell responses are better correlates of vaccine protection in the elderly. J. Immunol. 176, 6333-6339.
47. McElhaney, J. E., Zhou, X., Talbot, H. K., Soethout, E., Bleackley, R. C., Granville, D. J., et al. (2012). The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines. Vaccine 30, 2060-2067. doi:10.1016/j.vaccine.2012.01.015
48. Meier, J., and Sturm, A. (2009). The intestinal epithelial barrier: does it become impaired with age? Dig. Dis. 27, 240-245. doi:10.1159/000228556
49. Miller, E., Andrews, N., Stellitano, L., Stowe, J., Winstone, A. M., Shneerson, J., et al. (2013). Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. BMJ 346, f794. doi:10.1136/bmj.f794
50. Montecino-Rodriguez, E., Berent-Maoz, B., and Dorshkind, K. (2013). Causes, consequences, and reversal of immune system aging. J. Clin. Invest. 123, 958-965. doi:10.1172/JCI64096
51. Monto, A. S., Davenport, F. M., Napier, J. A., and Francis, T. Jr. (1969). Effect of vaccination of a school-age population upon the course of an A2-Hong Kong influenza epidemic. Bull. World Health Organ. 41, 537-542.
52. Nguyen, C. T., Kim, S. Y., Kim, M. S., Lee, S. E., and Rhee, J. H. (2011). Intranasal immunization with recombinant PspA fused with a flagellin enhances cross-protective immunity against Streptococcus pneumoniae infection in mice. Vaccine 29, 5731-5739. doi:10.1016/j.vaccine.2011.05.095
53. O'Hagan, D. T., Ott, G. S., De Gregorio, E., and Seubert, A. (2012). The mechanism of action of MF59-an innately attractive adjuvant formulation. Vaccine 30, 4341-4348. doi:10.1016/j.vaccine.2011.09.061
54. Olivieri, F., Rippo, M. R., Prattichizzo, F., Babini, L., Graciotti, L., Recchioni, R., et al. (2013). Toll like receptor signaling in "inflammaging": microRNA as new players. Immun. Ageing 10, 11. doi:10.1186/1742-4933-10-11
55. Ongradi, J., and Kovesdi, V. (2011). Numerical alterations of ageing B lymphocyte subsets. Acta Physiol. Hung. 98, 99-104. doi:10.1556/APhysiol.98.2011.2.1
56. Paula, C., Motta, A., Schmitz, C., Nunes, C. P., Souza, A. P., and Bonorino, C. (2009). Alterations in dendritic cell function in aged mice: potential implications for immunotherapy design. Biogerontology 10, 13-25. doi:10.1007/s10522-008-9150-x
57. Pereira, L. F., De Souza, A. P., Borges, T. J., and Bonorino, C. (2011). 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. 132, 187-194. doi:10.1016/j.mad
58. Pitman, R. J., Nagy, L. D., and Sculpher, M. J. (2013). Cost-effectiveness of childhood influenza vaccination in England and Wales: results from a dynamic transmission model. Vaccine 31, 927-942. doi:10.1016/j.vaccine.2012.12.010
59. Prelog, M. (2012). Differential approaches for vaccination from childhood to old age. Gerontology 3, 230-239. doi:10.1159/000343475
60. Prevention, C. F. D. C. A. (2013). Interim adjusted estimates of seasonal influenza vaccine effectiveness - United States, February 2013. MMWR Morb. Mortal. Wkly. Rep. 62. Available at: http://www.cdc.gov/mmwr/pdf/wk/mm6207.pdf
61. Ray, G. T., Whitney, C. G., Fireman, B. H., Ciuryla, V., and Black, S. B. (2006). Cost-effectiveness of pneumococcal conjugate vaccine: evidence from the first 5 years of use in the United States incorporating herd effects. Pediatr. Infect. Dis. J. 25, 494-501. doi:10.1097/01.inf.0000222403.42974.8b
62. Reimer, J. M., Karlsson, K. H., Lovgren-Bengtsson, K., Magnusson, S. E., Fuentes, A., and Stertman, L. (2012). Matrix-M adjuvant induces local recruitment, activation and maturation of central immune cells in absence of antigen. PLoS ONE 7, e41451. doi:10.1371/journal.pone.0041451
63. Salo, H., Kilpi, T., Sintonen, H., Linna, M., Peltola, V., and Heikkinen, T. (2006). Cost-effectiveness of influenza vaccination of healthy children. Vaccine 24, 4934-4941. doi:10.1016/j.vaccine.2006.03.057
64. Sarzotti, M., Robbins, D. S., and Hoffman, P. M. (1996). Induction of protective CTL responses in newborn mice by a murine retrovirus. Science 271, 1726-1728. doi:10.1126/science.271.5256.1726
65. Sasaki, S., Sullivan, M., Narvaez, C. F., Holmes, T. H., Furman, D., Zheng, N. Y., et al. (2011). Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. J. Clin. Invest. 121, 3109-3119. doi:10.1172/JCI57834
66. Skountzou, I., Martin Mdel, P., Wang, B., Ye, L., Koutsonanos, D., Weldon, W., et al. (2010). Salmonella flagellins are potent adjuvants for intranasally administered whole inactivated influenza vaccine. Vaccine 28, 4103-4112. doi:10.1016/j.vaccine.2009.07.058
67. Sun, L., Brown, R., Chen, S., Zhuge, Q., and Su, D. M. (2012). Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus. Aging (Albany NY) 4, 606-619.
68. Tan, S. Y., Cavanagh, L. L., D'advigor, W., Shackel, N., De St Groth, B., and Weninger, W. (2012). Phenotype and functions of conventional dendritic cells are not compromised in aged mice. Immunol. Cell Biol. 90, 722-732. doi:10.1038/icb.2011.104
69. Tan, T., Trindade, E., and Skowronski, D. (2005). Epidemiology of pertussis. Pediatr. Infect. Dis. J. 24, S10-S18. doi:10.1097/01.inf.0000160708.43944.99
70. Taylor, D. N., Treanor, J. J., Sheldon, E. A., Johnson, C., Umlauf, S., Song, L., et al. (2012). Development of VAX128, a recombinant hemagglutinin (HA) influenza-flagellin fusion vaccine with improved safety and immune response. Vaccine 30, 5761-5769. doi:10.1016/j.vaccine.2012.06.086
71. Tetsutani, K., and Ishii, K. J. (2012). Adjuvants in influenza vaccines. Vaccine 30, 7658-7661. doi:10.1016/j.vaccine.2012.10.007
72. Thomas, R. E., Jefferson, T., and Lasserson, T. J. (2010). Influenza vaccination for healthcare workers who work with the elderly. Cochrane Database Syst. Rev. 2, CD005187. doi:10.1002/14651858.CD005187.pub3
73. Tollervey, J. R., and Lunyak, V. V. (2012). Epigenetics: judge, jury and executioner of stem cell fate. Epigenetics 7, 823-840. doi:10.4161/epi.21141
74. Towers, S., and Feng, Z. (2012). Social contact patterns and control strategies for influenza in the elderly. Math. Biosci. 240, 241-249. doi:10.1016/j.mbs.2012.07.007
75. Trzonkowski, P., Mysliwska, J., Pawelec, G., and Mysliwski, A. (2009). From bench to bedside and back: the SENIEUR Protocol and the efficacy of influenza vaccination in the elderly. Biogerontology 10, 83-94. doi:10.1007/s10522-008-9155-5
76. Tumpel, S., and Rudolph, K. L. (2012). The role of telomere shortening in somatic stem cells and tissue aging: lessons from telomerase model systems. Ann. N. Y. Acad. Sci. 1266, 28-39. doi:10.1111/j.1749-6632.2012.06547.x
77. Van Zant, G., and Liang, Y. (2012). Concise review: hematopoietic stem cell aging, life span, and transplantation. Stem Cells Transl. Med. 1, 651-657. doi:10.5966/sctm.2012-0033
78. Verschoor, C. P., Johnstone, J., Millar, J., Dorrington, M. G., Habibagahi, M., Lelic, A., et al. (2013). Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer. J. Leukoc. Biol. 93, 633-637. doi:10.1189/jlb.0912461
79. Whitney, C. G., Farley, M. M., Hadler, J., Harrison, L. H., Bennett, N. M., Lynfield, R., et al. (2003). Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N. Engl. J. Med. 348, 1737-1746. doi:10.1056/NEJMoa022823
80. Wilkinson, T. M., Li, C. K., Chui, C. S., Huang, A. K., Perkins, M., Liebner, J. C., et al. (2012). Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat. Med. 18, 274-280. doi:10.1038/nm.2612
81. Wong, C. P., Magnusson, K. R., and Ho, E. (2010). Aging is associated with altered dendritic cells subset distribution and impaired proinflammatory cytokine production. Exp. Gerontol. 45, 163-169. doi:10.1016/j.exger.2009.11.005
82. Xu, Y. P., Qi, R. Q., Chen, W., Shi, Y., Cui, Z. Z., Gao, X. H., et al. (2012). Aging affects epidermal Langerhans cell development and function and alters their miRNA gene expression profile. Aging (Albany NY) 4, 742-754.
83. Zhao, J., Legge, K., and Perlman, S. (2011). 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. 121, 4921-4930. doi:10.1172/JCI59777