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Immunity & Ageing
Published in: Immunity & Ageing 1/2020

01-12-2020 | Influenza Vaccination | Review

The immune response to influenza in older humans: beyond immune senescence

Authors: Janet E. McElhaney, Chris P. Verschoor, Melissa K. Andrew, Laura Haynes, George A. Kuchel, Graham Pawelec

Published in: Immunity & Ageing | Issue 1/2020

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Abstract

Despite widespread influenza vaccination programs, influenza remains a major cause of morbidity and mortality in older adults. Age-related changes in multiple aspects of the adaptive immune response to influenza have been well-documented including a decline in antibody responses to influenza vaccination and changes in the cell-mediated response associated with immune senescence. This review will focus on T cell responses to influenza and influenza vaccination in older adults, and how increasing frailty or coexistence of multiple (≥2) chronic conditions contributes to the loss of vaccine effectiveness for the prevention of hospitalization. Further, dysregulation of the production of pro- and anti-inflammatory mediators contributes to a decline in the generation of an effective CD8 T cell response needed to clear influenza virus from the lungs. Current influenza vaccines provide only a weak stimulus to this arm of the adaptive immune response and rely on re-stimulation of CD8 T cell memory related to prior exposure to influenza virus. Efforts to improve vaccine effectiveness in older adults will be fruitless until CD8 responses take center stage.
Literature
1.
Molinari NA, Ortega-Sanchez IR, Messonnier ML, Thompson WW, Wortley PM, Weintraub E, et al. The annual impact of seasonal influenza in the US: measuring disease burden and costs. Vaccine. 2007;25(27):5086–96.PubMedCrossRef
2.
Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA. 2003;289(2):179–86.PubMedCrossRef
3.
Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, et al. Influenza-associated hospitalizations in the United States. JAMA. 2004;292(11):1333–40.PubMedCrossRef
4.
Iuliano AD, Roguski KM, Chang HH, Muscatello DJ, Palekar R, Tempia S, et al. Estimates of global seasonal influenza-associated respiratory mortality: a modelling study. Lancet. 2018;391(10127):1285–300.PubMedCrossRef
5.
6.
7.
Corrales-Medina VF, Alvarez KN, Weissfeld LA, Angus DC, Chirinos JA, Chang CC, et al. Association between hospitalization for pneumonia and subsequent risk of cardiovascular disease. Jama. 2015;313(3):264–74.PubMedPubMedCentralCrossRef
8.
Kwong JC, Schwartz KL, Campitelli MA, Chung H, Crowcroft NS, Karnauchow T, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med. 2018;378(4):345–53.CrossRefPubMed
9.
Tate JA, Snitz BE, Alvarez KA, Nahin RL, Weissfeld LA, Lopez O, et al. Infection hospitalization increases risk of dementia in the elderly. Crit Care Med. 2014;42(5):1037–46.PubMedPubMedCentralCrossRef
10.
Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(Suppl 1):S4–9.PubMedCrossRef
11.
Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004;351(25):2611–8.PubMedCrossRef
12.
Toschke AM, Heuschmann PU, Wood O, Wolfe CD. Temporal relationship between influenza infections and subsequent first-ever stroke incidence. Age Ageing. 2009;38(1):100–3.PubMedCrossRef
13.
Vardeny O, Solomon SD. Influenza and heart failure: a catchy comorbid combination. JACC Heart Fail. 2019;7(2):118–20.PubMedCrossRef
14.
Panhwar MS, Kalra A, Gupta T, Kolte D, Khera S, Bhatt DL, et al. Effect of influenza on outcomes in patients with heart failure. JACC Heart Fail. 2019;7(2):112–7.PubMedCrossRef
15.
Collins JP, Campbell AP, Openo K, Farley MM, Cummings CN, Hill M, et al. Outcomes of immunocompromised adults hospitalized with laboratory-confirmed influenza in the United States, 2011-2015. Clin Infect Dis; 2019. [Epub ahead of print].
16.
Hak E, Wei F, Nordin J, Mullooly J, Poblete S, Nichol KL. Development and validation of a clinical prediction rule for hospitalization due to pneumonia or influenza or death during influenza epidemics among community-dwelling elderly persons. J Infect Dis. 2004;189(3):450–8.PubMedCrossRef
17.
Walker TA, Waite B, Thompson MG, McArthur C, Wong C, Baker MG, et al. Risk of severe influenza among adults with chronic medical conditions. J Infect Dis. 2020;221(2):183–90.PubMedCrossRef
18.
Metersky ML, Masterton RG, Lode H, File TM Jr, Babinchak T. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza. Int J Infect Dis. 2012;16(5):e321–31.PubMedCrossRef
19.
20.
21.
Seki M, Kosai K, Yanagihara K, Higashiyama Y, Kurihara S, Izumikawa K, et al. Disease severity in patients with simultaneous influenza and bacterial pneumonia. Intern Med. 2007;46(13):953–8.PubMedCrossRef
22.
Ballinger MN, Standiford TJ. Postinfluenza bacterial pneumonia: host defenses gone awry. J Interf Cytokine Res. 2010;30(9):643–52.CrossRef
23.
Shrestha S, Foxman B, Weinberger DM, Steiner C, Viboud C, Rohani P. Identifying the interaction between influenza and pneumococcal pneumonia using incidence data. Sci Transl Med. 2013;5(191):191ra84.PubMedPubMedCentralCrossRef
24.
Campigotto A, Mubareka S. Influenza-associated bacterial pneumonia; managing and controlling infection on two fronts. Expert Rev Anti-Infect Ther. 2015;13(1):55–68.PubMedCrossRef
25.
Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. 2005;352(17):1749–59.PubMedCrossRef
26.
Cardoso R, Rivera M, Czarny MJ, Knijnik L, Fernandes A, Blumenthal RS, et al. In-Hospital Management and Outcomes of Patients With Acute Myocardial Infarction and Influenza. Am J Cardiol. 2020;125(6):840–4.
27.
Barnes M, Heywood AE, Mahimbo A, Rahman B, Newall AT, Macintyre CR. Acute myocardial infarction and influenza: a meta-analysis of case-control studies. Heart. 2015;101(21):1738–47.PubMedCrossRef
28.
Ferrucci L, Guralnik JM, Pahor M, Corti MC, Havlik RJ. Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled. Jama. 1997;277(9):728–34.PubMedCrossRef
29.
Fraenkel M, Yitshak-Sade M, Beacher L, Carmeli M, Mandelboim M, Siris E, et al. Is the association between hip fractures and seasonality modified by influenza vaccination? An ecological study. Osteoporos Int. 2017;28(9):2611–7.PubMedCrossRef
30.
Andrew MK, MacDonald S, Ye L, Ambrose A, Boivin G, Diaz-Mitoma F, et al. Impact of frailty on influenza vaccine effectiveness and clinical outcomes: Experience from the Canadian Immunization Research Network (CIRN) Serious Outcomes Surveillance (SOS) Network 2011/12 Season. Ottawa: Canadian Immunization Conference; 2016.
31.
Cassini A, Colzani E, Pini A, Mangen MJ, Plass D, McDonald SA, et al. Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013. Euro Surveill. 2018;23(16).
32.
Ng C, Ye L, Noorduyn SG, Hux M, Thommes E, Goeree R, et al. Resource utilization and cost of influenza requiring hospitalization in Canadian adults: a study from the serious outcomes surveillance network of the Canadian immunization research network. Influenza Other Respir Viruses. 2018;12(2):232–40.PubMedPubMedCentralCrossRef
33.
Nikolich-Zugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018;19(1):10–9.CrossRefPubMed
34.
35.
Dugan HL, Henry C, Wilson PC. Aging and influenza vaccine-induced immunity. Cell Immunol. 2020;348:103998.
36.
Naismith E, Pangrazzi L, Grasse M, Keller M, Miggitsch C, Weinberger B, et al. Peripheral antibody concentrations are associated with highly differentiated T cells and inflammatory processes in the human bone marrow. Immun Ageing. 2019;16(1):21.PubMedPubMedCentralCrossRef
37.
Bergman H, Ferrucci L, Guralnik J, Hogan DB, Hummel S, Karunananthan S, et al. Frailty: an emerging research and clinical paradigm--issues and controversies. J Gerontol A Biol Sci Med Sci. 2007;62(7):731–7.PubMedCrossRef
38.
39.
Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc. 2007;55(5):780–91.PubMedPubMedCentralCrossRef
40.
Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci. 2004;59(3):255–63.PubMedCrossRef
41.
Stretton CM, Latham NK, Carter KN, Lee AC, Anderson CS. Determinants of physical health in frail older people: the importance of self-efficacy. Clin Rehabil. 2006;20(4):357–66.PubMedCrossRef
42.
Rockwood K, Rockwood MR, Mitnitski A. Physiological redundancy in older adults in relation to the change with age in the slope of a frailty index. J Am Geriatr Soc. 2010;58(2):318–23.PubMedCrossRef
43.
Song X, Mitnitski A, Rockwood K. Prevalence and 10-year outcomes of frailty in older adults in relation to deficit accumulation. J Am Geriatr Soc. 2010;58(4):681–7.PubMedCrossRef
44.
Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381(9868):752–62.PubMedCrossRef
45.
Hoover M, Rotermann M, Sanmartin C, Bernier J. Validation of an index to estimate the prevalence of frailty among community-dwelling seniors. Health Rep. 2013;24(9):10–7.PubMed
46.
Andrew MK, Shinde V, Ye L, Hatchette T, Haguinet F, Dos Santos G, et al. The importance of frailty in the assessment of trivalent inactivated influenza vaccine effectiveness against influenza-related hospitalization in elderly people. J Infect Dis. 2017;216(4):405–14.PubMedPubMedCentralCrossRef
47.
Brummel NE, Bell SP, Girard TD, Pandharipande PP, Jackson JC, Morandi A, et al. Frailty and subsequent disability and mortality among patients with critical illness. Am J Respir Crit Care Med. 2017;196(1):64–72.PubMedPubMedCentralCrossRef
48.
Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, et al. A global clinical measure of fitness and frailty in elderly people. Cmaj. 2005;173(5):489–95.PubMedPubMedCentralCrossRef
49.
Bauer JM, De Castro A, Bosco N, Romagny C, Diekmann R, Benyacoub J, et al. Influenza vaccine response in community-dwelling German prefrail and frail individuals. Immun Ageing. 2017;14:17.PubMedPubMedCentralCrossRef
50.
Zhang HT, McGrath LJ, Wyss R, Ellis AR, Sturmer T. Controlling confounding by frailty when estimating influenza vaccine effectiveness using predictors of dependency in activities of daily living. Pharmacoepidemiol Drug Saf. 2017;26(12):1500–6.PubMedPubMedCentralCrossRef
51.
Moehling KK, Nowalk MP, Lin CJ, Bertolet M, Ross TM, Carter CE, et al. The effect of frailty on HAI response to influenza vaccine among community-dwelling adults >/= 50 years of age. Hum Vaccin Immunother. 2018;14(2):361–7.
52.
Samson SI, Leventhal PS, Salamand C, Meng Y, Seet BT, Landolfi V, et al. Immunogenicity of high-dose trivalent inactivated influenza vaccine: a systematic review and meta-analysis. Expert Rev Vaccines. 2019;18(3):295–308.PubMedCrossRef
53.
Narang V, Lu Y, Tan C, Camous XFN, Nyunt SZ, Carre C, et al. Influenza vaccine-induced antibody responses are not impaired by frailty in the community-dwelling elderly with natural influenza exposure. Front Immunol. 2018;9:2465.PubMedPubMedCentralCrossRef
54.
Van Epps P, Tumpey T, Pearce MB, Golding H, Higgins P, Hornick T, et al. Preexisting immunity, not frailty phenotype, predicts influenza postvaccination titers among older veterans. Clin Vaccine Immunol. 2017;24(3):e00498–16.PubMedPubMedCentral
55.
Yao X, Hamilton RG, Weng NP, Xue QL, Bream JH, Li H, et al. Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults. Vaccine. 2011;29(31):5015–21.PubMedPubMedCentralCrossRef
56.
Loeb N, Andrew MK, Loeb M, Kuchel GA, Haynes L, McElhaney JE, et al. Frailty is associated with increased hemagglutinin-inhibition titres in a 4-year randomized trial comparing standard and high dose influenza vaccination. Open Forum Infect Dis; 2020. In Press.
57.
Nicolay U, Heijnen E, Nacci P, Patriarca PA, Leav B. Immunogenicity of aIIV3, MF59-adjuvanted seasonal trivalent influenza vaccine, in older adults >/=65 years of age: meta-analysis of cumulative clinical experience. Int J Infect Dis. 2019;85S:S1–9.PubMedCrossRef
58.
McElhaney JE, Andrew MK, McNeil SA. Estimating influenza vaccine effectiveness: evolution of methods to better understand effects of confounding in older adults. Vaccine. 2017;35(46):6269–74.PubMedCrossRef
59.
McNeil SA, Andrew MK, Ye L, Haguinet F, Hatchette TF, ElSherif M, et al. Interim estimates of 2014/15 influenza vaccine effectiveness in preventing laboratory-confirmed influenza-related hospitalisation from the serious outcomes surveillance network of the Canadian immunization research network, January 2015. Euro Surveill. 2015;20(5):21024.PubMedCrossRef
60.
Nichols MK, Andrew MK, Hatchette TF, Ambrose A, Boivin G, Bowie W, et al. Influenza vaccine effectiveness to prevent influenza-related hospitalizations and serious outcomes in Canadian adults over the 2011/12 through 2013/14 influenza seasons: a pooled analysis from the Canadian immunization research network (CIRN) serious outcomes surveillance (SOS network). Vaccine. 2018;36(16):2166–75.PubMedCrossRef
61.
Mulpuru S, Li L, Ye L, Hatchette T, Andrew MK, Ambrose A, et al. Effectiveness of influenza vaccination on hospitalizations and risk factors for severe outcomes in hospitalized patients with COPD. Chest. 2019;155(1):69–78.PubMedCrossRef
62.
Petrie JG, Ohmit SE, Cheng CK, Martin ET, Malosh RE, Lauring AS, et al. Influenza vaccine effectiveness against Antigenically drifted influenza higher than expected in hospitalized adults: 2014-2015. Clin Infect Dis. 2016;63(8):1017–25.PubMedCrossRef
63.
Effros RB. Role of T lymphocyte replicative senescence in vaccine efficacy. Vaccine. 2007;25(4):599–604.PubMedCrossRef
64.
Nguyen HH, Moldoveanu Z, Novak MJ, van Ginkel FW, Ban E, Kiyono H, et al. Heterosubtypic immunity to lethal influenza a virus infection is associated with virus-specific CD8(+) cytotoxic T lymphocyte responses induced in mucosa-associated tissues. Virology. 1999;254(1):50–60.PubMedCrossRef
65.
He F, Madhan S, Kwang J. Baculovirus vector as a delivery vehicle for influenza vaccines. Expert Rev Vaccines. 2009;8(4):455–67.PubMedCrossRef
66.
Grant EJ, Josephs TM, Loh L, Clemens EB, Sant S, Bharadwaj M, et al. Broad CD8(+) T cell cross-recognition of distinct influenza a strains in humans. Nat Commun. 2018;9(1):5427.PubMedPubMedCentralCrossRef
67.
McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983;309(1):13–7.PubMedCrossRef
68.
Wilkinson TM, Li CK, Chui CS, Huang AK, Perkins M, Liebner JC, et al. Preexisting influenza-specific CD4+ T cells correlate with disease protection against influenza challenge in humans. Nat Med. 2012;18(2):274–80.PubMedCrossRef
69.
Sridhar S, Begom S, Bermingham A, Hoschler K, Adamson W, Carman W, et al. Cellular immune correlates of protection against symptomatic pandemic influenza. Nat Med. 2013;19(10):1305–12.PubMedCrossRef
70.
McElhaney JE, Xie D, Hager WD, Barry MB, Wang Y, Kleppinger A, et al. T cell responses are better correlates of vaccine protection in the elderly. J Immunol. 2006;176(10):6333–9.PubMedCrossRef
71.
McElhaney JE, Ewen C, Zhou X, Kane KP, Xie D, Hager WD, et al. Granzyme B: correlates with protection and enhanced CTL response to influenza vaccination in older adults. Vaccine. 2009;27:2418–25.PubMedPubMedCentralCrossRef
72.
Shahid Z, Kleppinger A, Gentleman B, Falsey AR, McElhaney JE. Clinical and immunologic predictors of influenza illness among vaccinated older adults. Vaccine. 2010;28(38):6145–51.PubMedPubMedCentralCrossRef
73.
Scheifele DW, McNeil SA, Ward BJ, Dionne M, Cooper C, Coleman B, et al. Safety, immunogenicity, and tolerability of three influenza vaccines in older adults: results of a randomized, controlled comparison. Hum Vaccin Immunother. 2013;9(11):2460–73.PubMedPubMedCentralCrossRef
74.
Kumar A, McElhaney JE, Walrond L, Cyr TD, Merani S, Kollmann TR, et al. Cellular immune responses of older adults to four influenza vaccines: results of a randomized, controlled comparison. Hum Vaccin Immunother. 2017;13(9):2048–57.PubMedPubMedCentralCrossRef
75.
Linehan E, Fitzgerald DC. Ageing and the immune system: focus on macrophages. Eur J Microbiol Immunol (Bp). 2015;5(1):14–24.CrossRef
76.
Albright JM, Dunn RC, Shults JA, Boe DM, Afshar M, Kovacs EJ. Advanced age alters monocyte and macrophage responses. Antioxid Redox Signal. 2016;25(15):805–15.PubMedPubMedCentralCrossRef
77.
Plowden J, Renshaw-Hoelscher M, Engleman C, Katz J, Sambhara S. Innate immunity in aging: impact on macrophage function. Aging Cell. 2004;3(4):161–7.PubMedCrossRef
78.
Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL, et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell. 2012;11(5):867–75.PubMedCrossRef
79.
Halstead ES, Umstead TM, Davies ML, Kawasawa YI, Silveyra P, Howyrlak J, et al. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization. Respir Res. 2018;19(1):3.PubMedPubMedCentralCrossRef
80.
Duan M, Hibbs ML, Chen W. The contributions of lung macrophage and monocyte heterogeneity to influenza pathogenesis. Immunol Cell Biol. 2017;95(3):225–35.PubMedCrossRef
81.
82.
Loughran ST, Power PA, Maguire PT, McQuaid SL, Buchanan PJ, Jonsdottir I, et al. Influenza infection directly alters innate IL-23 and IL-12p70 and subsequent IL-17A and IFN-γ responses to pneumococcus in vitro in human monocytes. PLoS One. 2018;13(9):e0203521.PubMedPubMedCentralCrossRef
83.
Jochems SP, Marcon F, Carniel BF, Holloway M, Mitsi E, Smith E, et al. Inflammation induced by influenza virus impairs human innate immune control of pneumococcus. Nat Immunol. 2018;19(12):1299–308.PubMedPubMedCentralCrossRef
84.
Ge MQ, Ho AW, Tang Y, Wong KH, Chua BY, Gasser S, et al. NK cells regulate CD8+ T cell priming and dendritic cell migration during influenza a infection by IFN-gamma and perforin-dependent mechanisms. J Immunol. 2012;189(5):2099–109.PubMedCrossRef
85.
He XS, Draghi M, Mahmood K, Holmes TH, Kemble GW, Dekker CL, et al. T cell-dependent production of IFN-gamma by NK cells in response to influenza a virus. J Clin Invest. 2004;114(12):1812–9.PubMedPubMedCentralCrossRef
86.
Hwang I, Scott JM, Kakarla T, Duriancik DM, Choi S, Cho C, et al. Activation mechanisms of natural killer cells during influenza virus infection. PLoS One. 2012;7(12):e51858.PubMedPubMedCentralCrossRef
87.
Verbist KC, Rose DL, Cole CJ, Field MB, Klonowski KD. IL-15 participates in the respiratory innate immune response to influenza virus infection. PLoS One. 2012;7(5):e37539.PubMedPubMedCentralCrossRef
88.
Beli E, Clinthorne JF, Duriancik DM, Hwang I, Kim S, Gardner EM. Natural killer cell function is altered during the primary response of aged mice to influenza infection. Mech Ageing Dev. 2011;132(10):503–10.PubMedPubMedCentralCrossRef
89.
Denney L, Aitken C, Li CK, Wilson-Davies E, Kok WL, Clelland C, et al. Reduction of natural killer but not effector CD8 T lymphocytes in three consecutive cases of severe/lethal H1N1/09 influenza a virus infection. PLoS One. 2010;5(5):e10675.PubMedPubMedCentralCrossRef
90.
Welliver TP, Garofalo RP, Hosakote Y, Hintz KH, Avendano L, Sanchez K, et al. Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. J Infect Dis. 2007;195(8):1126–36.PubMedCrossRef
91.
Mao H, Tu W, Liu Y, Qin G, Zheng J, Chan PL, et al. Inhibition of human natural killer cell activity by influenza virions and hemagglutinin. J Virol. 2010;84(9):4148–57.PubMedPubMedCentralCrossRef
92.
Pulendran B, Maddur MS. Innate immune sensing and response to influenza. Curr Top Microbiol Immunol. 2015;386:23–71.PubMed
93.
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, et al. Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol. 2010;184(5):2518–27.PubMedCrossRef
94.
Behzad H, Huckriede A, Haynes L, Gentleman B, Coyle K, Wilschut JC, et al. GLA-SE, a synthetic TLR4 agonist, enhances T cell responses to influenza vaccine in older adults. J Infect Dis. 2012;205(3):466–73.PubMedCrossRef
95.
Metcalf TU, Cubas RA, Ghneim K, Cartwright MJ, Grevenynghe JV, Richner JM, et al. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors. Aging Cell. 2015;14(3):421–32.PubMedPubMedCentralCrossRef
96.
Olafsdottir TA, Lindqvist M, Nookaew I, Andersen P, Maertzdorf J, Persson J, et al. Comparative systems analyses reveal molecular signatures of clinically tested vaccine adjuvants. Sci Rep. 2016;6:39097.PubMedPubMedCentralCrossRef
97.
Heeke DS, Lin R, Rao E, Woo JC, McCarthy MP, Marshall JD. Identification of GLA/SE as an effective adjuvant for the induction of robust humoral and cell-mediated immune responses to EBV-gp350 in mice and rabbits. Vaccine. 2016;34(23):2562–9.PubMedCrossRef
98.
Zurli V, Gallotta M, Taccone M, Chiarot E, Brazzoli M, Corrente F, et al. Positive contribution of adjuvanted influenza vaccines to the resolution of bacterial superinfections. J Infect Dis. 2016;213(12):1876–85.PubMedCrossRef
99.
Haynes L, Eaton SM, Burns EM, Rincon M, Swain SL. Inflammatory cytokines overcome age-related defects in CD4 T cell responses in vivo. J Immunol. 2004;172(9):5194–9.PubMedCrossRef
100.
Zhou X, Hopkins JW, Wang C, Brahmakshatriya V, Swain SL, Kuchel GA, et al. IL-2 and IL-6 cooperate to enhance the generation of influenza-specific CD8 T cells responding to live influenza virus in aged mice and humans. Oncotarget. 2016;7(26):39171.PubMedPubMedCentral
101.
Zhou X, McElhaney JE. Age-related changes in memory and effector T cells responding to influenza a/H3N2 and pandemic a/H1N1 strains in humans. Vaccine. 2011;29(11):2169–77.PubMedPubMedCentralCrossRef
102.
McElhaney JE, Gravenstein S, Upshaw CM, Hooton JW, Krause P, Drinka P, et al. Granzyme B: a marker of risk for influenza in institutionalized older adults. Vaccine. 2001;19(27):3744–51.PubMedCrossRef
103.
Ray SJ, Franki SN, Pierce RH, Dimitrova S, Koteliansky V, Sprague AG, et al. The collagen binding alpha1beta1 integrin VLA-1 regulates CD8 T cell-mediated immune protection against heterologous influenza infection. Immunity. 2004;20(2):167–79.PubMedCrossRef
104.
Liang S, Mozdzanowska K, Palladino G, Gerhard W. Heterosubtypic immunity to influenza type a virus in mice. Effector mechanisms and their longevity. J Immunol. 1994;152(4):1653–61.PubMed
105.
Budimir N, de Haan A, Meijerhof T, Waijer S, Boon L, Gostick E, et al. Critical role of TLR7 signaling in the priming of cross-protective cytotoxic T lymphocyte responses by a whole inactivated influenza virus vaccine. PLoS One. 2013;8(5):e63163.PubMedPubMedCentralCrossRef
106.
Cowling BJ, Perera R, Valkenburg SA, Leung NHL, Iuliano AD, Tam YH, et al. Comparative Immunogenicity of Several Enhanced Influenza Vaccine Options for Older Adults: A Randomized, Controlled Trial. Clin Infect Dis; 2019. [Epub ahead of print].
107.
Dunkle LM, Izikson R, Patriarca P, Goldenthal KL, Muse D, Callahan J, et al. Efficacy of recombinant influenza vaccine in adults 50 years of age or older. N Engl J Med. 2017;376(25):2427–36.PubMedCrossRef
108.
McElhaney JE, Beran J, Devaster JM, Esen M, Launay O, Leroux-Roels G, et al. AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial. Lancet Infect Dis. 2013;13(6):485–96.PubMedCrossRef
109.
DiazGranados CA, Dunning AJ, Kimmel M, Kirby D, Treanor J, Collins A, et al. Efficacy of high-dose versus standard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635–45.PubMedCrossRef
110.
Dong W, Bhide Y, Sicca F, Meijerhof T, Guilfoyle K, Engelhardt OG, et al. Cross-protective immune responses induced by sequential influenza virus infection and by sequential vaccination with inactivated influenza vaccines. Front Immunol. 2018;9:2312.PubMedPubMedCentralCrossRef
111.
Co MD, Orphin L, Cruz J, Pazoles P, Green KM, Potts J, et al. In vitro evidence that commercial influenza vaccines are not similar in their ability to activate human T cell responses. Vaccine. 2009;27(2):319–27.PubMedCrossRef
112.
Talbot HK, Nian H, Zhu Y, Chen Q, Williams JV, Griffin MR. Clinical effectiveness of split-virion versus subunit trivalent influenza vaccines in older adults. Clin Infect Dis. 2015;60(8):1170–5.PubMedPubMedCentralCrossRef
Metadata
Title
The immune response to influenza in older humans: beyond immune senescence
Authors
Janet E. McElhaney
Chris P. Verschoor
Melissa K. Andrew
Laura Haynes
George A. Kuchel
Graham Pawelec
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2020
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-020-00181-1

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Can an effective SARS-CoV-2 vaccine be developed for the older population?

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

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