Vaccination in the elderly: The challenge of immune changes with aging

Seminars in Immunology - Tập 40 - Trang 83-94 - 2018
Annalisa Ciabattini1, Christine Nardini2,3,4, Francesco Santoro1, Paolo Garagnani3,5,6, Claudio Franceschi7, Donata Medaglini1
1Laboratory of Molecular Microbiology and Biotechnology, Department of Medical Biotechnologies, University of Siena, Viale Bracci 16, 53100, Siena, Italy
2CNR IAC "Mauro Picone", Via dei Taurini, 19, 00185, Roma, Italy
3Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, SE-171 77, Stockholm, Sweden
4Personal Genomics S.r.l., Via Roveggia, 43B, 37134, Verona, Italy
5Department of Experimental, Diagnostic and Specialty Medicine (DIMES) - University of Bologna,40139, Bologna, Italy
6Interdepartmental Centre 'L. Galvani' (CIG), University of Bologna, Via G. Petroni 26, 40139, Bologna, Italy
7IRCCS Institute of Neurological Sciences of Bologna, via Altura 3, 40139, Bologna, Italy

Tóm tắt

Từ khóa


Tài liệu tham khảo

World Health Organization, 2018

Weinberger, 2018, Vaccines for the elderly: current use and future challenges, Immun. Ageing A, 15, 3, 10.1186/s12979-017-0107-2

Bridges, 2015, Meeting the challenges of immunizing adults, Vaccine, 33, D114, 10.1016/j.vaccine.2015.09.054

Osterholm, 2012, Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis, Lancet Infect. Dis., 12, 36, 10.1016/S1473-3099(11)70295-X

Jefferson, 2005, Efficacy and effectiveness of influenza vaccines in elderly people: a systematic review, Lancet Lond. Engl., 366, 1165, 10.1016/S0140-6736(05)67339-4

Siegrist, 2009, B-cell responses to vaccination at the extremes of age, Nat. Rev. Immunol., 9, 185, 10.1038/nri2508

Medaglini, 2018, Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE): A vision for the vaccines of tomorrow, Vaccine, 36, 1136, 10.1016/j.vaccine.2017.11.069

Rappuoli, 2011, Vaccines for the twenty-first century society, Nat. Rev. Immunol., 11, 865, 10.1038/nri3085

Franceschi, 2017, Immunobiography and the heterogeneity of immune responses in the elderly: A focus on inflammaging and trained immunity, Front. Immunol., 8, 982, 10.3389/fimmu.2017.00982

Pawelec, 2018, Age and immunity: what is “immunosenescence”?, Exp. Gerontol., 105, 4, 10.1016/j.exger.2017.10.024

Akbar, 2016, Senescence of T lymphocytes: implications for enhancing human immunity, Trends Immunol., 37, 866, 10.1016/j.it.2016.09.002

Johnson, 2004, Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity, Arthritis Res. Ther., 6, 131, 10.1186/ar1180

Schmitt, 2013, The Th17/Treg balance is disturbed during aging, Exp. Gerontol., 48, 1379, 10.1016/j.exger.2013.09.003

Vescovini, 2004, Different contribution of EBV and CMV infections in very long-term carriers to age-related alterations of CD8+ T cells, Exp. Gerontol., 39, 1233, 10.1016/j.exger.2004.04.004

Tu, 2016, Mechanisms underlying T cell immunosenescence: aging and cytomegalovirus infection, Front. Microbiol., 7, 2111, 10.3389/fmicb.2016.02111

Ogawa, 2000, Age-related changes of human bone marrow: a histometric estimation of proliferative cells, apoptotic cells, T cells, B cells and macrophages, Mech. Ageing Dev., 117, 57, 10.1016/S0047-6374(00)00137-8

Linton, 2004, Age-related changes in lymphocyte development and function, Nat. Immunol., 5, 133, 10.1038/ni1033

Sun, 2012, Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus, Aging (Albany NY), 606, 10.18632/aging.100487

Pang, 2011, Human bone marrow hematopoietic stem cells are increased in frequency and myeloid-biased with age, Proc. Natl. Acad. Sci. U. S. A., 108, 20012, 10.1073/pnas.1116110108

Leins, 2018, Aged murine hematopoietic stem cells drive aging-associated immune remodeling, Blood, 132, 565, 10.1182/blood-2018-02-831065

Kirkland, 2002, Adipogenesis and aging: does aging make fat go MAD?, Exp. Gerontol., 37, 757, 10.1016/S0531-5565(02)00014-1

Min, 2005, Effects of aging on early B- and T-cell development, Immunol. Rev., 205, 7, 10.1111/j.0105-2896.2005.00263.x

Gibson, 2009, B-cell diversity decreases in old age and is correlated with poor health status, Aging Cell., 8, 18, 10.1111/j.1474-9726.2008.00443.x

Frasca, 2015, MicroRNAs miR-155 and miR-16 decrease AID and E47 in B cells from elderly individuals, J. Immunol. Baltim. Md 1950, 195, 2134

Frasca, 2008, Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells, J. Immunol. Baltim. Md 1950, 180, 5283

Colonna-Romano, 2009, A double-negative (IgD-CD27-) B cell population is increased in the peripheral blood of elderly people, Mech. Ageing Dev., 130, 681, 10.1016/j.mad.2009.08.003

Martorana, 2014, Double negative (CD19+IgG+IgD−CD27−) B lymphocytes: A new insight from telomerase in healthy elderly, in centenarian offspring and in Alzheimer’s disease patients, Immunol. Lett., 162, 303, 10.1016/j.imlet.2014.06.003

Frasca, 2017, Human peripheral late/exhausted memory B cells express a senescent-associated secretory phenotype and preferentially utilize metabolic signaling pathways, Exp. Gerontol., 87, 113, 10.1016/j.exger.2016.12.001

Manley, 2011, Structure and function of the thymic microenvironment, Front. Biosci. Landmark Ed., 16, 2461, 10.2741/3866

Fagnoni, 2000, Shortage of circulating naive CD8(+) T cells provides new insights on immunodeficiency in aging, Blood, 95, 2860, 10.1182/blood.V95.9.2860.009k35_2860_2868

Sansoni, 2014, New advances in CMV and immunosenescence, Exp. Gerontol., 55, 54, 10.1016/j.exger.2014.03.020

Goronzy, 2013, Understanding immunosenescence to improve responses to vaccines, Nat. Immunol., 14, 428, 10.1038/ni.2588

Pera, 2015, Immunosenescence: implications for response to infection and vaccination in older people, Maturitas., 82, 50, 10.1016/j.maturitas.2015.05.004

Eaton, 2004, Age-related defects in CD4 T cell cognate helper function lead to reductions in humoral responses, J. Exp. Med., 200, 1613, 10.1084/jem.20041395

Bektas, 2017, Human T cell immunosenescence and inflammation in aging, J. Leukoc. Biol., 102, 977, 10.1189/jlb.3RI0716-335R

Franceschi, 2000, Inflamm-aging: an evolutionary perspective on immunosenescence, Ann. N. Y. Acad. Sci., 908, 244, 10.1111/j.1749-6632.2000.tb06651.x

Calder, 2017, Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition, Ageing Res. Rev., 40, 95, 10.1016/j.arr.2017.09.001

Franceschi, 2018, Inflammaging: a new immune–metabolic viewpoint for age-related diseases, Nat. Rev. Endocrinol., 1

Franceschi, 2007, Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans, Mech. Ageing Dev., 128, 92, 10.1016/j.mad.2006.11.016

Bauer, 2016, The role of oxidative and inflammatory stress and persistent viral infections in immunosenescence, Mech. Ageing Dev., 158, 27, 10.1016/j.mad.2016.01.001

Franceschi, 2017, Inflammaging and “Garb-aging,”, Trends Endocrinol. Metab. TEM., 28, 199, 10.1016/j.tem.2016.09.005

Biagi, 2012, Ageing of the human metaorganism: the microbial counterpart, AGE, 34, 247, 10.1007/s11357-011-9217-5

McElhaney, 2016, T-cell immunity to influenza in older adults: A pathophysiological framework for development of more effective vaccines, Front. Immunol., 7, 41, 10.3389/fimmu.2016.00041

Balmer, 2014, Microbiota-derived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling, J. Immunol. Baltim. Md 1950, 193, 5273

Zhang, 2015, Neutrophil ageing is regulated by the microbiome, Nature, 525, 528, 10.1038/nature15367

Josefsdottir, 2017, Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota, Blood, 129, 729, 10.1182/blood-2016-03-708594

Thevaranjan, 2017, Age-associated microbial dysbiosis promotes intestinal permeability, systemic inflammation, and macrophage dysfunction, Cell. Host Microbe., 21, 455, 10.1016/j.chom.2017.03.002

Deriu, 2016, Influenza virus affects intestinal microbiota and secondary salmonella infection in the gut through Type I interferons, PLoS Pathog., 12, e1005572, 10.1371/journal.ppat.1005572

Biagi, 2013, Ageing and gut microbes: perspectives for health maintenance and longevity, Pharmacol. Res., 69, 11, 10.1016/j.phrs.2012.10.005

World Health Organization, 2017

Grohskopf, 2015, Prevention and control of influenza with vaccines: recommendations of the advisory committee on immunization practices, United States, 2015–16 influenza season, MMWR Morb. Mortal. Wkly. Rep., 64, 818, 10.15585/mmwr.mm6430a3

2018, European Centre for Disease Prevention and Control, Seasonal influenza vaccination strategies, Eur. Cent. Dis. Prev. Control.

Belshe, 2010, The need for quadrivalent vaccine against seasonal influenza, Vaccine, 28, D45, 10.1016/j.vaccine.2010.08.028

Co, 2009, In vitro evidence that commercial influenza vaccines are not similar in their ability to activate human T cell responses, Vaccine, 27, 319, 10.1016/j.vaccine.2008.09.092

Frasca, 2010, Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans, Vaccine., 28, 8077, 10.1016/j.vaccine.2010.10.023

McElhaney, 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, 10.1016/S1473-3099(13)70046-X

Frasca, 2012, Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine, Int. Immunol., 24, 175, 10.1093/intimm/dxr123

Frasca, 2015, Aging, cytomegalovirus (CMV) and influenza vaccine responses, Hum. Vaccines Immunother., 12, 682, 10.1080/21645515.2015.1105413

Frasca, 2015, Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine, Vaccine, 33, 1433, 10.1016/j.vaccine.2015.01.071

Falsey, 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, 10.1086/599790

Tsang, 2014, Immunogenicity and safety of Fluzone(®) intradermal and high-dose influenza vaccines in older adults ≥65 years of age: a randomized, controlled, phase II trial, Vaccine., 32, 2507, 10.1016/j.vaccine.2013.09.074

O’Hagan, 2013, The history of MF59(®) adjuvant: a phoenix that arose from the ashes, Expert Rev. Vaccines, 12, 13, 10.1586/erv.12.140

DiazGranados, 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, 10.1016/j.vaccine.2012.12.013

Chen, 2011, Antibody and Th1-type cell-mediated immune responses in elderly and young adults immunized with the standard or a high dose influenza vaccine, Vaccine, 29, 2865, 10.1016/j.vaccine.2011.02.017

Nestle, 1993, Characterization of dermal dendritic cells obtained from normal human skin reveals phenotypic and functionally distinctive subsets, J. Immunol., 151, 6535, 10.4049/jimmunol.151.11.6535

Durando, 2011, Adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine, Hum. Vaccin., 7, 29, 10.4161/hv.7.0.14560

Mannino, 2012, Effectiveness of adjuvanted influenza vaccination in elderly subjects in northern Italy, Am. J. Epidemiol., 176, 527, 10.1093/aje/kws313

Villa, 2013, Safety of MF59-adjuvanted influenza vaccination in the elderly: results of a comparative study of MF59-adjuvanted vaccine versus nonadjuvanted influenza vaccine in northern Italy, Am. J. Epidemiol., 178, 1139, 10.1093/aje/kwt078

van Essen, 2014, Influenza symptoms and their impact on elderly adults: randomised trial of AS03-adjuvanted or non-adjuvanted inactivated trivalent seasonal influenza vaccines, Influenza Other Respir. Viruses., 8, 452, 10.1111/irv.12245

Garçon, 2012, Development and evaluation of AS03, an adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion, Expert Rev. Vaccines., 11, 349, 10.1586/erv.11.192

Klucker, 2012, AF03, an alternative squalene emulsion‐based vaccine adjuvant prepared by a phase inversion temperature method, J. Pharm. Sci., 101, 4490, 10.1002/jps.23311

Trucchi, 2015, Influenza vaccination in the elderly: why are the overall benefits still hotly debated?, J. Prev. Med. Hyg., 56, E37

Domnich, 2017, Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly: A systematic review and meta-analysis, Vaccine, 35, 513, 10.1016/j.vaccine.2016.12.011

Mori, 2008, Confounding in evaluating the effectiveness of influenza vaccine, Vaccine, 26, 6459, 10.1016/j.vaccine.2008.06.040

Drijkoningen, 2014, Pneumococcal infection in adults: burden of disease, Clin. Microbiol. Infect. Off. Publ. Eur. Soc. Clin. Microbiol. Infect. Dis., 20, 45

van Deursen, 2017, Immunogenicity of the 13-valent pneumococcal conjugate vaccine in older adults with and without comorbidities in the community-acquired pneumonia immunization trial in adults (CAPiTA), Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am., 65, 787, 10.1093/cid/cix419

Suzuki, 2017, Adult Pneumonia Study Group-Japan (APSG-J), serotype-specific effectiveness of 23-valent pneumococcal polysaccharide vaccine against pneumococcal pneumonia in adults aged 65 years or older: a multicentre, prospective, test-negative design study, Lancet Infect. Dis., 17, 313, 10.1016/S1473-3099(17)30049-X

Kawai, 2014, Systematic review of incidence and complications of herpes zoster: towards a global perspective, BMJ Open, 4, e004833, 10.1136/bmjopen-2014-004833

Izurieta, 2017, Effectiveness and duration of protection provided by the live-attenuated herpes zoster vaccine in the medicare population ages 65 years and older, Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am., 64, 785, 10.1093/cid/ciw854

Lal, 2015

Levin, 2018, Th1 memory differentiates recombinant from live herpes zoster vaccines, J. Clin. Invest., 10.1172/JCI121484

Di Pasquale, 2015, Vaccine adjuvants: from 1920 to 2015 and beyond, Vaccines., 3, 320, 10.3390/vaccines3020320

Cunningham, 2016

Lecrenier, 2018, Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention, Expert Rev. Vaccines, 17, 619, 10.1080/14760584.2018.1495565

Nicholson, 2011, Immunogenicity and safety of a two-dose schedule of whole-virion and AS03A-adjuvanted 2009 influenza A (H1N1) vaccines: a randomised, multicentre, age-stratified, head-to-head trial, Lancet Infect. Dis., 11, 91, 10.1016/S1473-3099(10)70296-6

Calabro, 2013, The adjuvant effect of MF59 is due to the oil-in-water emulsion formulation, none of the individual components induce a comparable adjuvant effect, Vaccine., 31, 3363, 10.1016/j.vaccine.2013.05.007

Del Giudice, 2015, Inactivated and adjuvanted influenza vaccines, Curr. Top. Microbiol. Immunol., 386, 151

Garçon, 2017, From discovery to licensure, the adjuvant system story, Hum. Vaccines Immunother., 13, 19, 10.1080/21645515.2016.1225635

Morel, 2011, Adjuvant system AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity, Vaccine, 29, 2461, 10.1016/j.vaccine.2011.01.011

Meier, 2011, Antibody responses to natural influenza A/H1N1/09 disease or following immunization with adjuvanted vaccines, in immunocompetent and immunocompromised children, Vaccine, 29, 3548, 10.1016/j.vaccine.2011.02.094

Rahier, 2011, European Crohn's and Colitis Organisation (ECCO), H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy, Gut, 60, 456, 10.1136/gut.2010.233981

Kosalaraksa, 2015, AS03B-adjuvanted H5N1 influenza vaccine in children 6 months through 17 years of age: a phase 2/3 randomized, placebo-controlled, observer-blinded trial, J. Infect. Dis., 211, 801, 10.1093/infdis/jiu548

Leroux-Roels, 2012, A phase 1/2 clinical trial evaluating safety and immunogenicity of a varicella zoster glycoprotein e subunit vaccine candidate in young and older adults, J. Infect. Dis., 206, 1280, 10.1093/infdis/jis497

Chlibek, 2014, Safety and immunogenicity of three different formulations of an adjuvanted varicella-zoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study, Vaccine, 32, 1745, 10.1016/j.vaccine.2014.01.019

Nakaya, 2016, Systems biology of immunity to MF59-adjuvanted versus nonadjuvanted trivalent seasonal influenza vaccines in early childhood, Proc. Natl. Acad. Sci., 113, 1853, 10.1073/pnas.1519690113

Awate, 2013, Mechanisms of action of adjuvants, Front. Immunol., 4, 114, 10.3389/fimmu.2013.00114

Ciabattini, 2016, Modulation of primary immune response by different vaccine adjuvants, Front. Immunol., 7, 427, 10.3389/fimmu.2016.00427

Ciabattini, 2018, Heterologous prime-boost combinations highlight the crucial role of adjuvant in priming the immune system, Front. Immunol., 9, 380, 10.3389/fimmu.2018.00380

Santoro, 2018, Transcriptomics of the vaccine immune response: priming with adjuvant modulates recall innate responses after boosting, Front. Immunol., 9, 1248, 10.3389/fimmu.2018.01248

Knudsen, 2016, Different human vaccine adjuvants promote distinct antigen-independent immunological signatures tailored to different pathogens, Sci. Rep., 6, 19570, 10.1038/srep19570

Olafsdottir, 2016, Comparative systems analyses reveal molecular signatures of clinically tested vaccine adjuvants, Sci. Rep., 6, 39097, 10.1038/srep39097

Wilkins, 2017, AS03- and MF59-Adjuvanted influenza vaccines in children, Front. Immunol., 8, 10.3389/fimmu.2017.01760

Ciabattini, 2015, Characterization of the antigen-specific CD4(+) T cell response induced by prime-boost strategies with CAF01 and CpG adjuvants administered by the intranasal and subcutaneous routes, Front. Immunol., 6, 430, 10.3389/fimmu.2015.00430

Prota, 2015, Peptide-specific T helper cells identified by MHC class II tetramers differentiate into several subtypes upon immunization with CAF01 adjuvanted H56 tuberculosis vaccine formulation, Vaccine, 33, 6823, 10.1016/j.vaccine.2015.09.024

Del Giudice, 2018, Correlates of adjuvanticity: A review on adjuvants in licensed vaccines, Semin. Immunol., 10.1016/j.smim.2018.05.001

Baker, 1988, Biomarkers of aging, Exp. Gerontol., 23, 223, 10.1016/0531-5565(88)90025-3

Deelen, 2013, Identifying the genomic determinants of aging and longevity in human population studies: progress and challenges, BioEssays News Rev. Mol. Cell. Dev. Biol., 35, 386, 10.1002/bies.201200148

Horvath, 2013, DNA methylation age of human tissues and cell types, Genome Biol., 14, R115, 10.1186/gb-2013-14-10-r115

Hannum, 2013, Genome-wide methylation profiles reveal quantitative views of human aging rates, Mol. Cell., 49, 359, 10.1016/j.molcel.2012.10.016

Blackburn, 2006, Telomeres and telomerase: the path from maize, tetrahymena and yeast to human cancer and aging, Nat. Med., 12, 1133, 10.1038/nm1006-1133

Holly, 2013, Towards a gene expression biomarker set for human biological age, Aging Cell, 12, 324, 10.1111/acel.12044

Putin, 2016, Deep biomarkers of human aging: application of deep neural networks to biomarker development, Aging, 8, 1021, 10.18632/aging.100968

Vanhooren, 2010, Serum N-glycan profile shift during human ageing, Exp. Gerontol., 45, 738, 10.1016/j.exger.2010.08.009

Levine, 2015, DNA methylation age of blood predicts future onset of lung cancer in the women’s health initiative, Aging, 7, 690, 10.18632/aging.100809

Marioni, 2015, DNA methylation age of blood predicts all-cause mortality in later life, Genome Biol., 16, 25, 10.1186/s13059-015-0584-6

Chen, 2016, DNA methylation-based measures of biological age: meta-analysis predicting time to death, Aging, 8, 1844, 10.18632/aging.101020

Marioni, 2015, The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936, Int. J. Epidemiol., 44, 1388, 10.1093/ije/dyu277

Horvath, 2015, Accelerated epigenetic aging in Down syndrome, Aging Cell., 14, 491, 10.1111/acel.12325

Jylhävä, 2017, Biological age predictors, EBioMedicine, 21, 29, 10.1016/j.ebiom.2017.03.046

Belsky, 2018, Eleven telomere, epigenetic clock, and biomarker-composite quantifications of biological aging: do they measure the same thing?, Am. J. Epidemiol., 187, 1220

Nardini, 2018, The epigenetics of inflammaging, Semin. Immunol., 10.1016/j.smim.2018.10.009

Fish, 2008, The X-files in immunity: sex-based differences predispose immune responses, Nat. Rev. Immunol., 8, 737, 10.1038/nri2394

Wikby, 2008, The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20-100 years of age, Biogerontology, 9, 299, 10.1007/s10522-008-9138-6

Kamada, 2001, B cell subsets in postmenopausal women and the effect of hormone replacement therapy, Maturitas, 37, 173, 10.1016/S0378-5122(00)00180-8

Deguchi, 2001, Postmenopausal changes in production of type 1 and type 2 cytokines and the effects of hormone replacement therapy, Menopause N. Y. N., 8, 266, 10.1097/00042192-200107000-00008

Furman, 2014, Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination, Proc. Natl. Acad. Sci., 111, 869, 10.1073/pnas.1321060111

Engler, 2008, Walter Reed Health Care System Influenza Vaccine Consortium, Half- vs full-dose trivalent inactivated influenza vaccine (2004–2005): age, dose, and sex effects on immune responses, Arch. Intern. Med., 168, 2405, 10.1001/archinternmed.2008.513

Manicklal, 2013, The “silent” global burden of congenital cytomegalovirus, Clin. Microbiol. Rev., 26, 86, 10.1128/CMR.00062-12

Merani, 2017, Impact of aging and cytomegalovirus on immunological response to influenza vaccination and infection, Front. Immunol., 8, 784, 10.3389/fimmu.2017.00784

Clement, 2016, Cytomegalovirus-specific IL-10-producing CD4+ T cells are governed by Type-I IFN-induced IL-27 and promote virus persistence, PLoS Pathog., 12, e1006050, 10.1371/journal.ppat.1006050

Querec, 2009, Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans, Nat. Immunol., 10, 116, 10.1038/ni.1688

Gaucher, 2008, Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses, J. Exp. Med., 205, 3119, 10.1084/jem.20082292

Bucasas, 2011, Early patterns of gene expression correlate with the humoral immune response to influenza vaccination in humans, J. Infect. Dis., 203, 921, 10.1093/infdis/jiq156

Furman, 2013, Apoptosis and other immune biomarkers predict influenza vaccine responsiveness, Mol. Syst. Biol., 9, 659, 10.1038/msb.2013.15

Nakaya, 2011, Systems biology of vaccination for seasonal influenza in humans, Nat. Immunol., 12, 786, 10.1038/ni.2067

Li, 2014, Molecular signatures of antibody responses derived from a systems biology study of five human vaccines, Nat. Immunol., 15, 195, 10.1038/ni.2789

Li, 2017, Metabolic phenotypes of response to vaccination in humans, Cell., 169, 862, 10.1016/j.cell.2017.04.026

Qi, 2016, Defective T memory cell differentiation after varicella zoster vaccination in older individuals, PLOS Pathog., 12, e1005892, 10.1371/journal.ppat.1005892

van den Berg, 2017, Predicting RTS,S vaccine-mediated protection from transcriptomes in a malaria-challenge clinical trial, Front. Immunol., 8, 557, 10.3389/fimmu.2017.00557

Kazmin, 2017, Systems analysis of protective immune responses to RTS,S malaria vaccination in humans, Proc. Natl. Acad. Sci. U. S. A., 114, 2425, 10.1073/pnas.1621489114

Vahey, 2010, Expression of genes associated with immunoproteasome processing of major histocompatibility complex peptides is indicative of protection with adjuvanted RTS,S malaria vaccine, J. Infect. Dis., 201, 580, 10.1086/650310

Reif, 2009, Integrated analysis of genetic and proteomic data identifies biomarkers associated with adverse events following smallpox vaccination, Genes Immun., 10, 112, 10.1038/gene.2008.80

Medaglini, 2017, Immunomonitoring of human responses to the rVSV-ZEBOV Ebola vaccine, Curr. Opin. Virol., 23, 88, 10.1016/j.coviro.2017.03.008

Medaglini, 2015, VSV-Ebovac Consortium, Ebola vaccine R&D: Filling the knowledge gaps, Sci. Transl. Med., 7, 317ps24, 10.1126/scitranslmed.aad3106

Medaglini, 2018, Correlates of vaccine-induced protective immunity against Ebola virus disease, Semin. Immunol., 10.1016/j.smim.2018.07.003

Rechtien, 2017, Systems vaccinology identifies an early innate immune signature as a correlate of antibody responses to the ebola vaccine rVSV-ZEBOV, Cell. Rep., 20, 2251, 10.1016/j.celrep.2017.08.023

Zak, 2012, Merck Ad5/HIV induces broad innate immune activation that predicts CD8+ T-cell responses but is attenuated by preexisting Ad5 immunity, Proc. Natl. Acad. Sci. U. S. A., 109, E3503, 10.1073/pnas.1208972109

Hoek, 2015, A cell-based systems biology assessment of human blood to monitor immune responses after influenza vaccination, PloS One, 10, e0118528, 10.1371/journal.pone.0118528

Ulijaszek, 2012, Socio-economic status, forms of capital and obesity, J. Gastrointest. Cancer, 43, 3, 10.1007/s12029-012-9366-5

Sansom, 2016, Metabolic disorders: how can systems modelling help?, Lancet Diabetes Endocrinol., 4, 306, 10.1016/S2213-8587(16)00047-4