, A role for antigen in the maintenance of immunogenical memory, Nature Reviews Immunology, vol.2, p.60, 2002.

. Site-de-l'oms,

, Activation, différenciation et mémoire des lymphocytes B. Immunologie, Le cours de Janis Kuby 7éme édition

. Vaccination-info-service and . Fr, Vaccins vivants atténués, 2018.

. Vaccination-info-service and . Fr, Vaccins inactivés ou inertes, 2018.

V. I. Partie, Le système immunitaire chez l'Homme sain et l'Homme malade. CHAPITRE 17. Maladies infectieuses et vaccination. Immunologie, Le cours de Janis Kurby 7éme édition

V. I. Partie, Le système immunitaire chez l'Homme sain et l'Homme malade. CHAPITRE 17. Maladies infectieuses et vaccination. Immunologie, Le cours de Janis Kurby 7éme édition, p.584

, Site de l'ANSM. Dossier : Les adjuvants. Disponible à l'adresse suivante

A. Banzhoff, R. Gasparini, F. Laghi-pasini, T. Staniscia, P. Durando et al., MF59-adjuvanted H5N1 vaccine induces immunologic memory and heterotypic antibody responses in non-elderly and elderly adults, Plos One, vol.4, p.4384, 2009.

J. Boyle, D. Eastman, C. Millar, S. Camuglia, J. Cox et al., The utility of ISCOMATRIX adjuvant for dose reduction of antigen for vaccines requiring antibody responses, Vaccine, vol.25, pp.2541-2545, 2007.

T. F. Schwarz, T. Horacek, M. Knuf, H. G. Damman, F. Roman et al., Single dose vaccination with AS03-adjuvanted H5N1 vaccines in a randomized trial induces strong and broad immune responsiveness to booster vaccination in adults, Vaccine, vol.27, pp.6284-90, 2009.

S. Sasaki, F. Takeshita, K. Q. Xin, N. Ishiii, and K. Okuda, Adjuvant formulations and delivery systems for DNA vaccines, Methods, vol.31, pp.243-54, 2003.

G. Galli, D. Medini, E. Borgogni, L. Zedda, M. Bardelli et al., Adjuvanted H5N1 vaccine induces early CD4+ T-cell response that predicts long-term persistence of protective antibody levels, Proc Natl Acad Sci, vol.106, pp.3877-82, 2009.

I. Leroux-roels, F. Roman, S. Forgus, C. Maes, D. Boever et al., Priming with AS03 A-adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: An open non-randomised extension of a double-blind randomised primary study, Vaccine, vol.28, pp.849-57, 2010.

P. Vandepapeliere, Y. Horsmans, P. Moris, M. Van-mechelen, M. Janssens et al., Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T-cell responses against hepatitis B surface antigen in healthy adult volunteers, Vaccine, vol.26, pp.1375-86, 2008.

G. Galli, K. Hancock, K. Hoschler, J. Devos, M. Praus et al., Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine, Proc Natl Acad Sci, vol.106, pp.7962-7969, 2009.

S. Khurana, W. Chearwae, F. Castellino, J. Manischewitz, L. R. King et al., Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus, Sci Transl Med, vol.2, pp.15-20, 2010.

J. W. Huleatt, A. R. Jacobs, J. Tang, P. Desai, E. B. Kopp et al., Vaccination with recombinant fusion proteins incorporating Toll-like receptor ligands induces rapid cellular and humoral immunity, Vaccine, vol.25, pp.763-75, 2007.

L. Malherbe, L. Mark, N. Fazilleau, L. J. Mcheyzer-williams, and M. Mg, Vaccine adjuvants alters TCR-based selection thresholds, Immunity, vol.28, pp.698-709, 2008.

V. I. Partie, Le système immunitaire chez l'Homme sain et l'Homme malade. CHAPITRE 17. Maladies infectieuses et vaccination. Immunologie, Le cours de Janis Kurby 7éme édition, p.585

, Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling

A. L. Gavin, K. Hoebe, B. Duong, T. Ota, C. Martin et al., Science, vol.314, issue.5807, pp.1936-1944, 2006.

D. A. Piggott, S. C. Eisenbarth, L. Xu, S. L. Constant, J. W. Huleatt et al., MyD88-dependent induction of allergic Th2 responses to intranasal antigen, J Clin Invest, vol.115, issue.2, pp.459-67, 2005.

S. C. Eisenbarth, O. R. Colegio, O. William, . Connor, F. S. Jr et al., Crucial role for the Nalp3inflammasome in the immunostimulatory properties of aluminium adjuvants, Nature, vol.453, issue.7198, pp.1122-1128, 2008.

, Mechanism of Immunopotentiation and Safety of Aluminum Adjuvants, Harm HogenEsch. Front Immunol, vol.3, p.406, 2012.

, Advances in aluminium hydroxyde-based adjuvant research and its mechanism. Peng He, Yening Zou, Zhongyu Hu. Hum Vaccin Immunother, vol.11, pp.477-488, 2015.

, The adjuvanted influenza vaccines with novel adjuvants: Experience with the MF59-adjuvanted vaccine, Podda A. Vaccine, vol.19, pp.2673-80, 2001.

G. A. Weinberg and P. G. Szilagyi, Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly : A systematic review and meta-analysis, Vaccine epidemiology: efficacy, effectiveness, and the translational research roadmap, vol.201, pp.513-520, 2010.

, The perfect mix: recent progress in adjuvant research, Nat. Rev. Microbiol, vol.5, pp.505-517, 2007.

N. Garçon, P. Chomez, and M. Van-mechelen, Adjuvant Systems in vaccines: concepts, achievements and perspectives, GlaxoSmithKline. Expert. Rev. Vaccines, vol.6, pp.723-739, 2007.

J. Paavonen, D. Jenkins, F. X. Bosch, P. Naud, J. Salmerón et al., Efficacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomised controlled trial, Lancet, vol.369, pp.2161-2170, 2007.

D. M. Harper, E. L. Franco, C. Wheeler, D. G. Ferris, D. Jenkins et al., Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and 18 in young women: a randomised controlled trial, Lancet, vol.364, pp.1757-1765, 2004.

D. M. Harper, E. L. Franco, and C. M. Wheeler, Lancet, vol.16, pp.1247-1255, 2006.

, New hepatitis B vaccine formulated with an improved adjuvant system, Expert. Rev. Vaccines, vol.6, pp.133-140, 2007.

N. Qureshi, K. Takayama, and E. Ribi, Purification and structural determination of nontoxic lipid A obtained from the lipopolysaccharide of Salmonella typhimurium, J. Biol. Chem, vol.257, pp.11808-11815, 1982.

J. R. Baldridge, P. Mcgowan, J. T. Evans, C. Cluff, S. Mossman et al., Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents, Expert Opin. Biol. Ther, vol.4, pp.1129-1138, 2004.

C. R. and T. C. Mitchell, Putting endotoxin to work for us: monophosphoryl lipid A as a safe and effective vaccine adjuvant. Casella, Cell Mol. Life Sci, vol.65, pp.3231-3240, 2008.

M. Hirschfeld, Y. Ma, J. H. Weis, S. N. Vogel, and J. J. Weis, Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine, J. Immunol, vol.165, pp.618-622, 2000.

R. I. Tapping, S. Akashi, K. Miyake, P. J. Godowski, and P. S. Tobias, Toll-like receptor 4, but not Toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides, J. Immunol, vol.165, pp.5780-5787, 2000.

, Enhancement of antigen-specific immunity via the TLR4 ligands MPL adjuvant and Ribi

J. T. Evans, C. W. Cluff, D. A. Johnson, M. J. Lacy, D. H. Persing et al., Expert Rev. Vaccines, vol.529, pp.219-229, 2003.

M. Martin, S. M. Michalek, and J. Katz, Role of innate immune factors in the adjuvant activity of monophosphoryl lipid A, Infect. Immun, vol.71, pp.2498-2507, 2003.

A. Tiberio, L. , L. Fletcher, J. H. Eldridge, and D. D. Duncan, Host factors impacting the innate response in humans to the candidate adjuvants RC529 and monophosphoryl, Vaccine, vol.22, pp.1515-1523, 2004.

A. Iwasaki and R. Medzhitov, Toll-like receptor control of the adaptive immune responses, Nat. Immunol, vol.5, pp.987-995, 2004.

R. Medzhitov, Toll pathway-dependent blockade of CD4 + CD25 + T cell-mediated suppression by dendritic cells. Pasare, C, Science, vol.299, pp.1033-1036, 2003.

S. J. Olshansky, D. Perry, R. A. Miller, and R. N. Butler, Pursuing the longevity dividend: scientific goals for an aging world, Ann NY Acad Sci, vol.1114, pp.11-13, 2007.

, Chronic disease and medical innovation in an aging nation. The Silver Book. Published by the Alliance for Aging Research, 2011.

C. López-otín, M. A. Blasco, L. Partridge, M. Serrano, and G. Kroemer, The hallmarks of aging, Cell, vol.63, pp.1194-1217, 2013.

. Inflamm-ageing, E. Cevenini, D. Monti, and C. Franceschi, Curr Opin Clin Nutr Metab Care, vol.18, pp.14-20, 2013.

, The role of DNA damage and repair in aging through the prism of Koch-like criteria

A. A. Moskalev, M. V. Shaposhnikov, E. N. Plyusnina, A. Zhavoronkov, A. Budovsky et al., Ageing Res Rev, vol.12, issue.2, pp.661-84, 2013.

, DNA damage, aging, and cancer. Hoeijmakers JH, N Engl J Med, 2009.

, The DNA damage response and cancer therapy. Lord CJ, Ashworth A. Nature, vol.481, pp.287-94, 2012.

L. Kazak, A. Reyes, and I. J. Holt, Minimizing the damage: repair pathways keep mitochondrial DNA intact, Nat Rev Mol Cell Biol, vol.13, issue.10, pp.659-71, 2012.

. Nuclear and . Worman, , vol.226, pp.316-341, 2012.

D. J. Baker, M. M. Dawlaty, T. Wijshake, K. B. Jeganathan, L. Malureanu et al., Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan, Nat Cell Biol, vol.15, issue.1, pp.96-102, 2013.

E. H. Blackburn, C. W. Greider, and J. W. Szostak, Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging, Nat Med, vol.12, issue.10, pp.1133-1141, 2006.

, The serial cultivation of human diploid cell strains. Hayflick L, Moorheads PS, Exp Cell Res, pp.585-621, 1961.

, Telomeres, telomerase, and aging: origin of the theory. Olovnikov AM

A. G. Bodnar, M. Ouellette, M. Frolkis, S. E. Holt, C. P. Chiu et al., Extension of life-span by introduction of telomerase into normal human cells, vol.279, pp.349-52, 1998.

, How shelterin protects mammalian telomeres. Palm W, de Lange T, Annu Rev Genet, vol.42, pp.301-335, 2008.

G. Hewitt, D. Jurk, F. D. Marques, C. Correia-melo, T. Hardy et al., Telomeres are favoured targets of a persistent DNA damage response in ageing and stressinduced senescence, Nat Commun, vol.3, p.708, 2012.

, Short telomeres are sufficient to cause the degenerative defects associated with aging

M. Armanios, J. K. Alder, E. M. Parry, B. Karim, M. A. Strong et al., Am J Hum Genet, vol.85, issue.6, pp.823-855, 2009.

K. L. Rudolph, S. Chang, H. W. Lee, M. Blasco, G. J. Gottlieb et al., Longevity, stress response, and cancer in aging telomerase-deficient mice, Cell, vol.96, issue.5, pp.701-713, 1999.

A. Tomás-loba, I. Flores, P. J. Fernández-marcos, M. L. Cayuela, A. Maraver et al., Telomerase reverse transcriptase delays aging in cancer-resistant mice, vol.135, pp.609-631, 2008.

, Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice

M. Jaskelioff, F. L. Muller, J. H. Paik, E. Thomas, S. Jiang et al., Nature, vol.469, issue.7328, pp.102-108, 2011.

J. B. Bernardes-de, E. Vera, K. Schneeberger, A. M. Tejera, E. Ayuso et al., Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer, EMBO Mol Med, vol.4, issue.8, pp.691-704, 2012.

K. Schneeberger, E. Vera, A. Tejera, C. B. Harley, and M. A. Blasco, The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence, Bernardes de Jesus B, vol.10, issue.4, pp.604-625, 2011.

J. J. Boonekamp, M. J. Simons, L. Hemerik, and S. Verhulst, Telomere length behaves as biomarker of somatic redundancy rather than biological age, Aging Cell, vol.12, issue.2, pp.330-332, 2013.

I. Telomeres and . Competency, Nan-ping Weng, vol.24, pp.470-475, 2012.

R. P. Talens, K. Christensen, H. Putter, G. Willemsen, L. Christiansen et al., Epigenetic variation during the adult lifespan: cross-sectional and longitudinal data on monozygotic twin pairs, Aging Cell, vol.11, issue.4, pp.694-703, 2012.

, Epigenetics and aging: the targets and the marks. Fraga MF, Esteller M. Trends Genet, vol.23, pp.413-421, 2007.

S. Han and A. Brunet, Histone methylation makes its mark on longevity, Trends Cell Biol, vol.22, issue.1, pp.42-51, 2012.

. Reprogramming, J. M. Freije, and C. López-otín, Curr Opin Cell Biol, vol.24, issue.6, pp.757-64, 2012.

T. A. Rando and H. Y. Chang, Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock, Cell, vol.148, issue.1-2, pp.46-57, 2012.

, Altered histone acetylation is associated with age-dependent memory impairment in mice

S. Peleg, F. Sananbenesi, A. Zovoilis, S. Burkhardt, S. Bahari-javan et al., , vol.328, pp.753-759, 2010.

V. Krishnan, M. Z. Chow, Z. Wang, L. Zhang, B. Liu et al., Histone H4 lysine 16 hypoacetylation is associated with defective DNA repair and premature senescence in Zmpste24-deficient mice, Proc Natl Acad Sci, vol.108, issue.30, pp.12325-12355, 2011.

E. L. Greer, T. J. Maures, D. Ucar, A. G. Hauswirth, E. Mancini et al., Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans, Nature, vol.479, issue.7373, pp.365-71, 2011.

E. T. Powers, R. I. Morimoto, A. Dillin, J. W. Kelly, and W. E. Balch, Biological and chemical approaches to diseases of proteostasis deficiency, Annu Rev Biochem, vol.78, pp.959-91, 2009.

, Molecular chaperones in protein folding and proteostasis. Hartl FU, Bracher A, Hayer-Hartl M. Nature, vol.475, pp.324-356, 2011.

H. Koga, S. Kaushik, and A. M. Cuervo, Protein homeostasis and aging: The importance of exquisite quality control, Ageing Res Rev, vol.10, issue.2, pp.205-220, 2011.

N. Mizushima, B. Levine, A. M. Cuervo, and D. J. Klionsky, Autophagy fights disease through cellular self-digestion, Nature, vol.451, issue.7182, pp.1069-75, 2008.

T. J. Van-ham, M. A. Holmberg, A. T. Van-der-goot, E. Teuling, M. Garcia-arencibia et al., /SERF as a regulator of age-related proteotoxicity, vol.142, pp.601-613, 2010.

, Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Zhang C, Cuervo AM, Nat Med, vol.14, issue.9, pp.959-65, 2008.

. Angela-m-phillips, O. Luna, E. E. Gonzalez, A. I. Nekongo, S. M. Ponomarenko et al., Host proteostasis modulates inflenza evolution, 2017.

N. Barzilai, D. M. Huffman, R. H. Muzumdar, and A. Bartke, The critical role of metabolic pathways in aging, Diabetes, vol.61, issue.6, pp.1315-1337, 2012.

L. Fontana, L. Partridge, V. D. Longo, and . Science, Extending healthy life span--from yeast to humans, vol.328, pp.321-327, 2010.

, The genetics of ageing. Kenyon CJ. Nature, vol.464, pp.504-516, 2010.

. Metabolic-networks-of-longevity, R. H. Houtkooper, R. W. Williams, J. Auwerx, and . Cell, , vol.142, pp.9-14, 2009.

D. E. Harrison, R. Strong, Z. D. Sharp, J. F. Nelson, C. M. Astle et al., Rapamycin fed late in life extends lifespan in genetically heterogeneous mice, Nature, 2009.

D. R. Green, L. Galluzzi, G. Kroemer, and . Science, Mitochondria and the autophagy-inflammation-cell death axis in organismal aging, vol.333, pp.1109-1121, 2011.

V. Calabrese, C. Cornelius, S. Cuzzocrea, I. Iavicoli, E. Rizzarelli et al., Hormesis, cellular stress response and vitagenes as critical determinants in aging and longevity, Mol Aspects Med, vol.32, pp.279-304, 2011.

, The aging stress response, Haigis MC, Yankner BA. Mol Cell, vol.40, issue.2, pp.333-377, 2010.

J. Durieux, S. Wolff, and D. A. Cell, The cell-non-autonomous nature of electron transport chain-mediated longevity, vol.144, pp.79-91, 2011.

, Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging

G. C. Kujoth, A. Hiona, T. D. Pugh, S. Someya, K. Panzer et al., , vol.309, pp.481-485, 2005.

A. Trifunovic, A. Wredenberg, M. Falkenberg, J. N. Spelbrink, A. T. Rovio et al., Premature ageing in mice expressing defective mitochondrial DNA polymerase, Nature, vol.429, issue.6990, pp.417-440, 2004.

M. Vermulst, J. Wanagat, G. C. Kujoth, J. H. Bielas, P. S. Rabinovitch et al., DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice, Nat Genet, vol.40, issue.4, pp.392-396, 2008.

A. Dashdorj, K. R. Jyothi, S. Lim, J. A. Nguyen, M. N. Ha et al., Mitochondria-targeted antioxidant MitoQ ameliorates experimental mouse colitis by suppressing NLRP3 inflammasome-mediated inflammatory cytokines, BMC Med, vol.11, p.178, 2013.

, NLRP3 inflammasome is activated in fibromyalgia: the effect of coenzyme Q10

M. D. Cordero, E. Alcocer-gómez, O. Culic, A. M. Carrión, M. De-miguel et al., Antioxid Redox Signal, vol.20, issue.8, pp.1169-80, 2014.

«. Aifm1-;-morton, S. U. Prabhu, S. P. Lidov, H. Shi, J. et al., mutation presenting with fatal encephalomyopathy and mitochondrial disease in an infant, vol.3, p.1560, 2017.

K. Fukumoto, T. B. Nguyen, S. Chiba, and M. Sakata-yanagimoto, Review of the biologic and clinical significance of genetic mutations in angioimmunoblastic T-cell lymphoma, Cancer Sci, vol.109, issue.3, pp.490-496, 2018.

, Cellular senescence: when bad things happen to good cells. Campisi J, d'Adda di Fagagna F, Nat Rev Mol Cell Biol, vol.8, issue.9, pp.729-769, 2007.

M. Collado, M. A. Blasco, M. Serrano, and . Cell, Cellular senescence in cancer and aging, vol.130, pp.223-256, 2007.

T. Kuilman, C. Michaloglou, W. J. Mooi, D. S. Peeper, and . Genes-dev, The essence of senescence, vol.24, pp.2463-79, 2010.

, A biomarker that identifies senescent human cells in culture and in aging skin in vivo

G. P. Dimri, X. Lee, G. Basile, M. Acosta, G. Scott et al., Proc Natl Acad Sci, vol.92, issue.20, pp.9363-9370, 1995.

C. Wang, D. Jurk, M. Maddick, G. Nelson, C. Martin-ruiz et al., DNA damage response and cellular senescence in tissues of aging mice, Aging Cell, vol.8, issue.3, pp.311-334, 2009.

, Immune surveillance of senescent cells--biological significance in cancer-and noncancer pathologies. Hoenicke L, Zender L, Carcinogenesis, vol.33, issue.6, pp.1123-1129, 2012.

, Senescence surveillance of pre-malignant hepatocytes limits liver cancer development

T. W. Kang, T. Yevsa, N. Woller, L. Hoenicke, T. Wuestefeld et al., Nature, vol.479, issue.7374, pp.547-51, 2009.

W. Xue, L. Zender, C. Miething, R. A. Dickins, H. E. Krizhanovsky et al., Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas, Nature, vol.445, issue.7128, pp.656-60, 2007.

A. Matheu, A. Maraver, M. Collado, I. Garcia-cao, M. Cañamero et al., Anti-aging activity of the Ink4/Arf locus, vol.8, pp.152-61, 2009.

A. Matheu, A. Maraver, P. Klatt, I. Flores, I. Garcia-cao et al., Delayed ageing through damage protection by the Arf/p53 pathway, vol.448, pp.375-384, 2007.

D. J. Baker, T. Wijshake, T. Tchkonia, N. K. Lebrasseur, B. G. Childs et al., Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders, Nature, vol.479, issue.7372, pp.232-238, 2011.

L. I. Prieto and D. J. Baker, Cellular Senecence and the Immune System in Cancer, vol.65, pp.505-512, 2019.

A. C. Shaw, S. Joshi, H. Greenwood, A. Panda, and J. M. Lord, Aging of the innate immune system, Curr Opin Immunol, vol.22, issue.4, pp.507-520, 2010.

A. V. Molofsky, S. G. Slutsky, N. M. Joseph, S. He, R. Pardal et al., Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing, Nature, vol.443, issue.7110, pp.448-52, 2006.

R. Gruber, H. Koch, B. A. Doll, F. Tegtmeier, T. A. Einhorn et al., Fracture healing in the elderly patient, Exp Gerontol, vol.41, issue.11, pp.1080-93, 2006.

, Heterochronic parabiosis for the study of the effects of aging on stem cells and their niches. Conboy IM, Rando TA. Cell Cycle, vol.11, pp.2260-2267, 2012.

D. J. Rossi, D. Bryder, J. Seita, A. Nussenzweig, J. Hoeijmakers et al., Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age, Nature, vol.447, issue.7145, pp.725-734, 2007.

V. Janzen, R. Forkert, H. E. Fleming, Y. Saito, M. T. Waring et al., Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a, Nature, vol.443, issue.7110, pp.421-427, 2006.

I. Flores, M. A. Blasco, and . Lett, The role of telomeres and telomerase in stem cell aging, vol.584, pp.3826-3856, 2010.

, How stem cells age and why this makes us grow old, Sharpless NE, DePinho RA. Nat Rev Mol Cell Biol, vol.8, issue.9, pp.703-716, 2007.

, Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog

M. Rera, S. Bahadorani, J. Cho, C. L. Koehler, M. Ulgherait et al., Cell Metab, vol.14, issue.5, pp.623-657, 2011.

J. V. Chakkalakal, K. M. Jones, M. A. Basson, and A. S. Brack, The aged niche disrupts muscle stem cell quiescence, Nature, vol.490, issue.7420, pp.355-60, 2012.

M. Laplante and D. M. Sabatini, mTOR signaling in growth control and disease, vol.149, pp.274-93, 2012.

T. A. Rando and H. Y. Chang, Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock, Cell, vol.148, issue.1-2, pp.46-57, 2012.

S. J. Russell and C. R. Kahn, Endocrine regulation of ageing, Nat Rev Mol Cell Biol, vol.8, issue.9, pp.681-91, 2007.

, Hypothalamic programming of systemic ageing involving IKK-?, NF-?B and GnRH

G. Zhang, J. Li, S. Purkayastha, Y. Tang, H. Zhang et al., Nature, vol.497, issue.7448, pp.211-217, 2009.

C. Inflamm-aging-;-franceschi, M. Bonafè, S. Valensin, F. Olivieri, D. Luca et al., An evolutionary perspective on immunosenescence, Ann N Y Acad Sci, pp.244-54, 0908.

. Inflammaging, C. Franceschi, M. Capri, D. Monti, S. Giunta et al., Mech Ageing Dev, vol.128, issue.1, pp.92-105, 2007.

C. Holmes, C. Cunningham, E. Zotova, J. Woolford, C. Dean et al., Systemic inflammation and disease progression in Alzheimer disease, vol.73, pp.768-74, 2009.

, Therapeutic agents for patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor-alpha antagonists, Isaacs JD. Expert Opin Biol Ther, 2009.

L. Association-between, E. Lindholm, E. Bakhtadze, C. Cilio, E. Agardh et al., PLoS One, vol.3, issue.6, p.2546, 2008.

I. Osteoporosis, P. G. Lacativa, and M. L. Farias, Arq Bras Endocrinol Metabol, vol.54, issue.2, pp.123-155, 2010.

P. Sarzi-puttini, F. Atzeni, A. Doria, L. Iaccarino, M. Turiel et al., Tumor necrosis factor-alpha, biologic agents and cardiovascular risk, vol.14, pp.780-784, 2005.

, The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis

D. Fishman, G. Faulds, R. Jeffery, M. , V. Yudkin et al., J Clin Invest, vol.102, issue.7, pp.1369-76, 1998.

R. Giacconi, C. Cipriano, F. Albanese, G. Boccoli, V. Saba et al., The -174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing, Exp Gerontol, vol.39, issue.4, pp.621-629, 2004.

F. Olivieri, M. Bonafè, L. Cavallone, S. Giovagnetti, F. Marchegiani et al., The -174 C/G locus affects in vitro/in vivo IL-6 production during aging, Exp Gerontol, 2002.

R. Giacconi, C. Cipriano, F. Albanese, G. Boccoli, V. Saba et al., The -174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing, Exp Gerontol, vol.39, issue.4, pp.621-629, 2004.

R. Antonicelli, F. Olivieri, M. Bonafè, L. Cavallone, L. Spazzafumo et al., The interleukin-6 -174 G>C promoter polymorphism is associated with a higher risk of death after an acute coronary syndrome in male elderly patients, Int J Cardiol, 2005.

, Genotype frequencies of the +874T-->A single nucleotide polymorphism in the first intron of the interferon-gamma gene in a sample of Sicilian patients affected by tuberculosis

D. Lio, V. Marino, A. Serauto, V. Gioia, L. Scola et al., Eur J Immunogenet, vol.29, issue.5, pp.371-375, 2002.

D. Lio, L. Scola, A. Crivello, M. Bonafè, C. Franceschi et al., Allele frequencies of +874T-->A single nucleotide polymorphism at the first intron of interferon-gamma gene in a group of Italian centenarians, Exp Gerontol, vol.37, issue.2-3, pp.315-324, 2002.

, A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production, Hum Immunol, vol.61, issue.9, pp.863-869, 2000.

, Gender-specific association between -1082 IL-10 promoter polymorphism and longevity

D. Lio, L. Scola, A. Crivello, G. Colonna-romano, G. Candore et al., Genes Immun, vol.3, issue.1, pp.30-33, 2002.

F. Haspot, A. Lavault, C. Sinzger, L. Sampaio, K. Stierhof et al., Human cytomegalovirus entry into dendritic cells occurs via a macropinocytosis-like pathway in a pH-independent and cholesterol-dependent manner, PLoS One, vol.7, issue.4, p.34795, 2012.

R. B. Freeman, The 'indirect' effects of cytomegalovirus infection, Am J Transplant, vol.9, issue.11, pp.2453-2461, 2009.

S. Prösch, K. Staak, J. Stein, C. Liebenthal, T. Stamminger et al., Stimulation of the human cytomegalovirus IE enhancer/promoter in HL-60 cells by TNFalpha is mediated via induction of NF-kappaB, vol.208, pp.197-206, 1995.

E. Sikora, T. Arendt, M. Bennett, and M. Narita, Impact of cellular senescence signature on ageing research, Ageing Res Rev, vol.10, issue.1, pp.146-52, 2011.

A. Freund, A. V. Orjalo, P. Y. Desprez, and J. Campisi, Inflammatory networks during cellular senescence: causes and consequences, Trends Mol Med, vol.16, issue.5, pp.238-284, 2010.

F. Olivieri, R. Lazzarini, R. Recchioni, F. Marcheselli, M. R. Rippo et al., MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling, Age (Dordr), vol.35, issue.4, pp.1157-72, 2013.

, Cellular senescence: putting the paradoxes in perspective, Campisi J. Curr Opin Genet Dev, vol.21, issue.1, pp.107-119, 2011.

, Cellular senescence and the senescent secretory phenotype: therapeutic opportunities

T. Tchkonia, Y. Zhu, J. Van-deursen, J. Campisi, and J. L. Kirkland, J Clin Invest, 2013.

L. K. Forsythe, J. M. Wallace, and M. B. Livingstone, Obesity and inflammation: the effects of weight loss, Nutr Res Rev, vol.21, issue.2, pp.117-150, 2008.

, Inflammation and metabolic disorders. Hotamisligil GS, Nature, 2006.

, The origins and drivers of insulin resistance, Johnson AM, Olefsky JM. Cell, vol.152, issue.4, pp.673-84, 2013.

. Inflammation, S. E. Shoelson, J. Lee, and A. B. Goldfine, J Clin Invest, vol.116, issue.7, pp.1793-801, 2006.

A. G. Renehan, M. Tyson, M. Egger, R. F. Heller, M. Zwahlen et al., Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies, vol.371, pp.569-78, 2008.

A. R. Setty, G. Curhan, and H. K. Choi, waist circumference, weight change, and the risk of psoriasis in women: Nurses' Health Study II, Arch Intern Med, 2007.

R. Casas, E. Sacanella, and R. Estruch, The immune protective effect of the Mediterranean diet against chronic low-grade inflammatory diseases, Endocr Metab Immune Disord Drug Targets, vol.14, issue.4, pp.245-54, 2014.

D. J. Hass, C. M. Brensinger, J. D. Lewis, and G. R. Lichtenstein, The impact of increased body mass index on the clinical course of Crohn's disease, Clin Gastroenterol Hepatol, 2006.

S. Nishimura, I. Manabe, M. Nagasaki, K. Eto, H. Yamashita et al., CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity, Nat Med, vol.15, issue.8, pp.914-934, 2009.

C. N. Lumeng, J. L. Bodzin, and A. R. Saltiel, Obesity induces a phenotypic switch in adipose tissue macrophage polarization, J Clin Invest, vol.117, issue.1, pp.175-84, 2007.

M. Fabbri, A. Paone, F. Calore, R. Galli, and C. M. Croce, A new role for microRNAs, as ligands of Toll-like receptors, vol.10, pp.169-74, 2013.

F. Olivieri, R. Lazzarini, R. Recchioni, F. Marcheselli, M. R. Rippo et al., MiR-146a as marker of senescence-associated pro-inflammatory status in cells involved in vascular remodelling, vol.35, pp.1157-72, 2013.

F. Olivieri, M. R. Rippo, A. D. Procopio, F. F. Fazioli, and . Genet, Circulating inflamma-miRs in aging and age-related diseases, vol.4, p.121, 2013.

Q. Zhang, M. Raoof, Y. Chen, Y. Sumi, T. Sursal et al., Circulating mitochondrial DAMPs cause inflammatory responses to injury, Nature, vol.464, issue.7285, pp.104-111, 2010.

M. Pinti, E. Cevenini, M. Nasi, D. Biasi, S. Salvioli et al., Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for "inflamm-aging, Eur J Immunol, vol.44, issue.5, pp.1552-62, 2014.

, You are what you host: microbiome modulation of the aging process. Heintz C, Mair W. Cell, vol.156, pp.408-419, 2014.

E. Biagi, M. Candela, S. Turroni, P. Garagnani, C. Franceschi et al., Ageing and gut microbes: perspectives for health maintenance and longevity, Pharmacol Res, vol.69, issue.1, pp.11-20, 2013.

E. Biagi, L. Nylund, M. Candela, R. Ostan, L. Bucci et al., Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians, vol.5, p.10667, 2010.

S. Mueller, K. Saunier, C. Hanisch, E. Norin, L. Alm et al., Differences in fecal microbiota in different European study populations in relation to age, gender, and country: a cross-sectional study, Appl Environ Microbiol, vol.72, issue.2, pp.1027-1060, 2006.

E. J. Woodmansey, M. E. Mcmurdo, G. T. Macfarlane, and S. Macfarlane, Comparison of compositions and metabolic activities of fecal microbiotas in young adults and in antibiotic-treated and non-antibiotic-treated elderly subjects, Appl Environ Microbiol, vol.70, issue.10, pp.6113-6135, 2004.

E. Biagi, L. Nylund, M. Candela, R. Ostan, L. Bucci et al., Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians, vol.5, p.10667, 2010.

M. Rajili?-stojanovi?, H. G. Heilig, D. Molenaar, K. Kajander, A. Surakka et al., Development and application of the human intestinal tract chip, a phylogenetic microarray: analysis of universally conserved phylotypes in the abundant microbiota of young and elderly adults, Environ Microbiol, vol.11, issue.7, pp.1736-51, 2009.

J. Meier and A. Sturm, The intestinal epithelial barrier: does it become impaired with age?, Dig Dis, vol.27, issue.3, pp.240-245, 2009.

S. K. Butcher, H. Chahal, L. Nayak, A. Sinclair, N. V. Henriquez et al., Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans, J Leukoc Biol, vol.70, issue.6, pp.881-887, 2001.

A. L. Brubaker, J. L. Rendon, L. Ramirez, M. A. Choudhry, E. Kovacs et al., Reduced neutrophil chemotaxis and infiltration contributes to delayed resolution of cutaneous wound infection with advanced age, vol.190, pp.1746-57, 2013.

E. Sapey, H. Greenwood, G. Walton, E. Mann, A. Love et al., Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence, vol.123, pp.239-287, 2009.

V. Nomellini, A. L. Brubaker, S. Mahbub, J. L. Palmer, C. R. Gomez et al., Dysregulation of neutrophil CXCR2 and pulmonary endothelial icam-1 promotes agerelated pulmonary inflammation, Aging Dis, vol.3, issue.3, pp.234-281, 2012.

, Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype

C. D. Wiley, M. C. Velarde, P. Lecot, S. Liu, E. A. Sarnoski et al., Cell Metab, vol.23, issue.2, pp.303-317, 2009.

, Neutrophils of centenarians show function levels similar to those of young adults

P. Alonso-fernández, M. Puerto, I. Maté, J. M. Ribera, and M. De-la-fuente, J Am Geriatr Soc, vol.56, issue.12, pp.2244-51, 2008.

, Blood Monocytes and Their Subsets: Established Features and Open Questions. Ziegler-Heitbrock L. Front Immunol, vol.6, p.423, 2015.

T. U. Metcalf, R. A. Cubas, K. Ghneim, M. J. Cartwright, J. V. Grevenynghe et al., Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors, Aging Cell, vol.14, issue.3, pp.421-453, 2015.

A. C. Hearps, G. E. Martin, T. A. Angelovich, W. J. Cheng, A. Maisa et al., Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function, Aging Cell, vol.11, issue.5, pp.867-75, 2012.

J. A. Mclachlan, C. D. Serkin, K. M. Morrey, O. Bakouche, and . Immunol, Antitumoral properties of aged human monocytes, vol.154, pp.832-875, 1995.

D. Van-duin, S. Mohanty, V. Thomas, S. Ginter, R. R. Montgomery et al., Age-associated defect in human TLR-1/2 function, J Immunol, vol.178, issue.2, pp.970-975, 2007.

F. Qian, X. Wang, L. Zhang, S. Chen, M. Piecychna et al., Age-associated elevation in TLR5 leads to increased inflammatory responses in the elderly, Aging Cell, vol.11, issue.1, pp.104-114, 2012.

, Flagellin as an adjuvant: cellular mechanisms and potential. Mizel SB, Bates JT, J Immunol, vol.185, issue.10, pp.5677-82, 2010.

M. Bhushan, M. Cumberbatch, R. J. Dearman, S. M. Andrew, I. Kimber et al., Tumour necrosis factor-alpha-induced migration of human Langerhans cells: the influence of ageing, Br J Dermatol, vol.146, issue.1, pp.32-40, 2002.

, Deterioration of the Langerhans cell network of the human gingival epithelium with aging. Zavala WD, Cavicchia JC, Arch Oral Biol, vol.51, issue.12, pp.1150-1155, 2006.

, Skin infections and ageing. Laube S, Ageing Res Rev, vol.3, issue.1, pp.69-89, 2004.

A. Agrawal, S. Agrawal, J. N. Cao, H. Su, K. Osann et al., Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway, vol.178, pp.6912-6934, 2007.

N. Janssen, E. Derhovanessian, I. Demuth, F. Arnaout, E. Steinhagen-thiessen et al., Responses of Dendritic Cells to TLR-4 Stimulation Are Maintained in the Elderly and Resist the Effects of CMV Infection Seen in the Young, J Gerontol A Biol Sci Med Sci, vol.71, issue.9, pp.1117-1140, 2016.

A. Panda, F. Qian, S. Mohanty, D. Van-duin, F. K. Newman et al., Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response, J Immunol, vol.184, issue.5, pp.2518-2545, 2010.

Y. Jing, E. Shaheen, R. R. Drake, N. Chen, S. Gravenstein et al., Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood, Hum Immunol, vol.70, issue.10, pp.777-84, 2009.

G. Emanuelli, M. Lanzio, T. Anfossi, S. Romano, G. Anfossi et al., Influence of age on polymorphonuclear leukocytes in vitro: phagocytic activity in healthy human subjects, Gerontology, vol.32, issue.6, pp.308-324, 1986.

M. P. Do-nascimento, K. H. Pinke, M. Penitenti, M. R. Ikoma, and V. S. Lara, Aging does not affect the ability of human monocyte-derived dendritic cells to phagocytose Candida albicans, Aging Clin Exp Res, vol.27, issue.6, pp.785-794, 2015.

. Immunosenescence, A. L. Gruver, L. L. Hudson, G. D. Sempowski, and . Pathol, , vol.211, pp.144-56, 2007.

M. Pinti, M. Nasi, E. Lugli, L. Gibellini, L. Bertoncelli et al., T cell homeostasis in centenarians: from the thymus to the periphery, vol.16, pp.597-603, 2010.

M. Nasi, L. Troiano, E. Lugli, M. Pinti, R. Ferraresi et al., Thymic output and functionality of the IL-7/IL-7 receptor system in centenarians: implications for the neolymphogenesis at the limit of human life, vol.5, pp.167-75, 2006.

E. Lugli, M. Pinti, M. Nasi, L. Troiano, R. Ferraresi et al., Subject classification obtained by cluster analysis and principal component analysis applied to flow cytometric data, Cytometry A, vol.71, issue.5, pp.334-378, 2007.

, Spatial map of human T cell compartmentalization and maintenance over decades of life

J. J. Thome, N. Yudanin, Y. Ohmura, M. Kubota, B. Grinshpun et al., , vol.159, pp.814-842, 2014.

G. Li, M. Yu, W. W. Lee, M. Tsang, E. Krishnan et al., Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity, Nat Med, vol.18, issue.10, pp.1518-1542, 2012.

O. Briceño, A. Lissina, K. Wanke, G. Afonso, A. Von-braun et al., ) T-cell priming efficacy in elderly adults, Aging Cell, vol.15, issue.1, pp.14-21, 2016.

J. M. Richner, G. B. Gmyrek, J. Govero, Y. Tu, G. J. Van-der-windt et al., Age-Dependent Cell Trafficking Defects in Draining Lymph Nodes Impair Adaptive Immunity and Control of West Nile Virus Infection, PLoS Pathog, vol.11, issue.7, p.1005027, 2015.

A. R. Schulz, J. N. Mälzer, C. Domingo, K. Jürchott, A. Grützkau et al., Low Thymic Activity and Dendritic Cell Numbers Are Associated with the Immune Response to Primary Viral Infection in Elderly Humans, J Immunol, vol.195, issue.10, pp.4699-711, 2015.

A. Ademokun, Y. C. Wu, D. Dunn-walters, . Biogerontology, D. Frasca et al., Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine, Int Immunol, vol.24, issue.3, pp.175-82, 2010.

D. Frasca, A. M. Landin, S. C. Lechner, J. G. Ryan, R. Schwartz et al., Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells, vol.180, pp.3262-3269, 2005.

J. F. Fecteau, G. Côté, and S. Néron, A new memory CD27-IgG+ B cell population in peripheral blood expressing VH genes with low frequency of somatic mutation, J Immunol, vol.177, issue.6, pp.3728-3764, 2006.

G. Colonna-romano, M. Bulati, A. Aquino, M. Pellicanò, S. Vitello et al., IgD-CD27-) B cell population is increased in the peripheral blood of elderly people, A double-negative, vol.130, pp.681-90, 2009.

K. Wistuba-hamprecht, D. Frasca, B. Blomberg, G. Pawelec, and E. Derhovanessian, Age-associated alterations in ?? T-cells are present predominantly in individuals infected with Cytomegalovirus, Immun Ageing, vol.10, issue.1, p.26, 2013.

D. Frasca, A. Diaz, M. Romero, A. M. Landin, and B. B. Blomberg, High TNF-? levels in resting B cells negatively correlate with their response, Exp Gerontol, pp.116-138, 2014.

D. Frasca, A. Diaz, M. Romero, N. V. Mendez, A. M. Landin et al., Effects of age on H1N1-specific serum IgG1 and IgG3 levels evaluated during the 2011-2012 influenza vaccine season, Immun Ageing, vol.10, issue.1, p.14, 2013.

S. Khurana, D. Frasca, B. Blomberg, and H. Golding, AID activity in B cells strongly correlates with polyclonal antibody affinity maturation in-vivo following pandemic 2009-H1N1 vaccination in humans, PLoS Pathog, vol.8, issue.9, p.1002920, 2012.

D. Frasca, A. M. Landin, S. C. Lechner, J. G. Ryan, R. Schwartz et al., Aging down-regulates the transcription factor E2A, activation-induced cytidine deaminase, and Ig class switch in human B cells, J Immunol, vol.180, issue.8, pp.5283-90, 2008.

D. Frasca, A. Diaz, M. Romero, A. M. Landin, and B. B. Blomberg, High TNF-? levels in resting B cells negatively correlate with their response, Exp Gerontol, pp.116-138, 2014.

G. Colonna-romano, M. Bulati, A. Aquino, M. Pellicanò, S. Vitello et al., IgD-CD27-) B cell population is increased in the peripheral blood of elderly people, A double-negative, vol.130, pp.681-90, 2009.

E. Derhovanessian, H. Theeten, K. Hähnel, P. Van-damme, N. Cools et al., Cytomegalovirus-associated accumulation of late-differentiated CD4 T-cells correlates with poor humoral response to influenza vaccination, vol.31, pp.685-90, 2013.

, 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

J. E. Mcelhaney, X. Zhou, H. K. Talbot, E. Soethout, R. C. Bleackley et al., , vol.30, pp.2060-2067, 2009.

T. Fulop, L. Page, A. Fortin, C. Witkowski, J. M. Dupuis et al., Cellular signaling in the aging immune system, Curr Opin Immunol, pp.105-116, 2014.

R. R. Montgomery and A. C. Shaw, Paradoxical changes in innate immunity in aging: recent progress and new directions, J Leukoc Biol, vol.98, issue.6, pp.937-980, 2015.

R. Solana, R. Tarazona, I. Gayoso, O. Lesur, G. Dupuis et al., Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans, Semin Immunol, vol.24, issue.5, pp.331-372, 2012.

E. Sapey, H. Greenwood, G. Walton, E. Mann, A. Love et al., Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence, vol.123, pp.239-287, 2009.

C. F. Fortin, A. Larbi, O. Lesur, N. Douziech, and T. Fulop, Impairment of SHP-1 down-regulation in the lipid rafts of human neutrophils under GM-CSF stimulation contributes to their age-related, altered functions, J Leukoc Biol, vol.79, issue.5, pp.1061-72, 2006.

R. Aspinall, A. Lapenna, C. B-lynch, and P. O. Lang, Cellular signalling pathways in immune aging and regeneration, Biochem Soc Trans, vol.42, issue.3, pp.651-657, 2014.

J. J. Goronzy, G. Li, M. Yu, and C. M. Weyand, Signaling pathways in aged T cells -a reflection of T cell differentiation, cell senescence and host environment, Semin Immunol, vol.24, issue.5, pp.365-72, 2012.

U. Ponnappan, G. U. Trebilcock, and M. Z. Zheng, Studies into the effect of tyrosine phosphatase inhibitor phenylarsine oxide on NFkappaB activation in T lymphocytes during aging: evidence for altered IkappaB-alpha phosphorylation and degradation, Exp Gerontol, vol.34, issue.1, pp.95-107, 1999.

, Downregulation of inhibitory SRC homology 2 domain-containing phosphatase-1 (SHP

L. Page, A. Fortin, C. Garneau, H. Allard, N. Tsvetkova et al., leads to recovery of T cell responses in elderly, Cell Commun Signal, vol.12, p.2, 2009.

A. Larbi, G. Dupuis, A. Khalil, N. Douziech, C. Fortin et al., Differential role of lipid rafts in the functions of CD4+ and CD8+ human T lymphocytes with aging, vol.18, pp.1017-1047, 2006.

A. Larbi, J. Kempf, and G. Pawelec, Oxidative stress modulation and T cell activation, Exp Gerontol, vol.42, issue.9, pp.852-860, 2007.

K. J. Lenton, H. Therriault, A. M. Cantin, T. Fülöp, H. Payette et al., Direct correlation of glutathione and ascorbate and their dependence on age and season in human lymphocytes, Am J Clin Nutr, vol.71, issue.5, pp.1194-200, 2000.

, Free radicals and redox signalling in T-cells during chronic inflammation and ageing

H. R. Griffiths, C. R. Dunston, S. J. Bennett, M. M. Grant, D. C. Phillips et al., Biochem Soc Trans, vol.39, issue.5, pp.1273-1281, 2011.

I. Ageing, G. Gavazzi, and K. H. Krause, Lancet Infect Dis, vol.2, issue.11, pp.659-66, 2002.

D. M. Fleming, R. J. Taylor, R. L. Lustig, C. Schuck-paim, F. Haguinet et al., Modelling estimates of the burden of Respiratory Syncytial virus infection in adults and the elderly in the United Kingdom, BMC Infect Dis, vol.15, p.443, 2015.

C. A. Shaw, M. Ciarlet, B. W. Cooper, L. Dionigi, P. Keith et al., The path to an RSV vaccine, Curr Opin Virol, vol.3, issue.3, pp.332-374, 2013.

A. S. Cross, W. H. Chen, and M. M. Levine, A case for immunization against nosocomial infections, J Leukoc Biol, vol.83, issue.3, pp.483-491, 2008.

, Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis

M. T. Osterholm, N. S. Kelley, A. Sommer, and E. A. Belongia, Lancet Infect Dis, vol.12, issue.1, pp.36-44, 2012.

W. E. Beyer, J. Mcelhaney, D. J. Smith, A. S. Monto, and J. S. Nguyen-van-tam, Cochrane re-arranged: support for policies to vaccinate elderly people against influenza, Osterhaus AD. Vaccine, vol.31, issue.50, pp.6030-6033, 2013.

B. Weinberger, M. Schirmer, M. Gothe, R. Siebert, U. Fuchs et al., Recall responses to tetanus and diphtheria vaccination are frequently insufficient in elderly persons, PLoS One, vol.8, issue.12, p.82967, 2013.

I. Ridda, J. K. Yin, C. King, R. Macintyre, C. Mcintyre et al., The importance of pertussis in older adults: a growing case for reviewing vaccination strategy in the elderly, vol.30, pp.6745-52, 2012.

M. Kaml, I. Weiskirchner, M. Keller, T. Luft, E. Hoster 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, vol.24, pp.6808-6819, 2006.

C. De-waure, M. A. Veneziano, C. Cadeddu, S. Capizzi, M. L. Specchia et al., Economic value of influenza vaccination, Hum Vaccin Immunother, vol.8, issue.1, pp.119-148, 2012.

, Mortality associated with influenza and respiratory syncytial virus in the United States

W. W. Thompson, D. K. Shay, E. Weintraub, L. Brammer, N. Cox et al., , vol.289, pp.179-86, 2003.

M. N. Oxman, M. J. Levin, G. R. Johnson, K. E. Schmader, S. E. Straus et al., A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults, N Engl J Med, vol.352, issue.22, pp.2271-84, 2005.

M. J. Bonten, S. M. Huijts, M. Bolkenbaas, C. Webber, S. Patterson et al., Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults, N Engl J Med, vol.372, issue.12, pp.1114-1139, 2015.

K. Goodwin, C. Viboud, L. Simonsen, and . Vaccine, Antibody response to influenza vaccination in the elderly: a quantitative review, vol.24, pp.1159-69, 2006.

, Influenza vaccine: the challenge of antigenic drift. Carrat F, Flahault A. Vaccine, vol.262, pp.6852-62, 2007.

J. K. Yin, G. Khandaker, H. Rashid, L. Heron, I. Ridda et al., Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis, vol.5, pp.299-305, 2011.

K. M. Gostic, M. Ambrose, M. Worobey, and L. Jo, Potent protection against H5N1 and H7N9 influenza via childhood hemagglutinin imprinting, Science, vol.354, issue.6313, pp.722-726, 2016.

, Efficacy of high-dose versus standard-dose influenza vaccine in older adults

C. A. Diazgranados, A. J. Dunning, M. Kimmel, D. Kirby, J. Treanor et al., N Engl J Med, vol.371, issue.7, pp.635-680, 2014.

, Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine

J. J. Treanor, J. D. Campbell, K. M. Zangwill, R. T. Wolff, M. Engl et al., Ch, vol.354, issue.13, pp.1343-51, 2006.

G. Del-giudice and R. Rappuoli, Inactivated and adjuvanted influenza vaccines, Curr Top Microbiol Immunol, vol.386, pp.151-80, 2015.

M. Vukmanovic-stejic, M. H. Rustin, J. Nikolich-zugich, and A. N. Akbar, Immune responses in the skin in old age, Curr Opin Immunol, vol.23, issue.4, pp.525-556, 2011.

S. M. Patel, R. L. Atmar, E. Sahly, H. M. Guo, K. Hill et al., Direct comparison of an inactivated subvirion influenza A virus subtype H5N1 vaccine administered by the intradermal and intramuscular routes, J Infect Dis, vol.206, issue.7, pp.1069-77, 2012.

R. B. Belshe, F. K. Newman, J. Cannon, C. Duane, J. Treanor et al., Serum antibody responses after intradermal vaccination against influenza, N Engl J Med, vol.351, issue.22, pp.2286-94, 2004.

P. Van-damme, R. Arnou, F. Kafeja, A. Fiquet, P. Richard et al., Evaluation of non-inferiority of intradermal versus adjuvanted seasonal influenza vaccine using two serological techniques: a randomised comparative study, BMC Infect Dis, vol.10, p.134, 2010.

L. B. Gelinck, B. J. Van-den-bemt, W. A. Marijt, A. E. Van-der-bijl, L. G. Visser et al., Intradermal influenza vaccination in immunocompromized patients is immunogenic and feasible, vol.27, pp.2469-74, 2009.

D. Gregorio, E. Tritto, E. Rappuoli, and R. , Alum adjuvanticity: unraveling a century old mystery, Eur J Immunol, vol.38, issue.8, pp.2068-71, 2008.

S. G. Reed, M. T. Orr, and C. B. Fox, Key roles of adjuvants in modern vaccines, Nat Med, vol.19, issue.12, pp.1597-608, 2013.

, Development of an AS04-adjuvanted HPV vaccine with the adjuvant system approach

N. Garçon, S. Morel, A. Didierlaurent, D. Descamps, M. Wettendorff et al., , vol.25, pp.217-243, 2011.

. Efficacy and S. Rts, AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial. RTS,S Clinical Trials Partnership, N Engl J Med, vol.386, issue.9988, pp.255-63, 2013.

I. Leroux-roels, G. Leroux-roels, F. Clement, P. Vandepapelière, V. Vassilev et al., 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, vol.206, issue.8, pp.1280-90, 2012.

R. Chlibek, J. Smetana, K. Pauksens, L. Rombo, J. A. Van-den-hoek et al., Safety and immunogenicity of three different formulations of an adjuvanted varicellazoster virus subunit candidate vaccine in older adults: a phase II, randomized, controlled study, vol.32, pp.1745-53, 2014.

H. Lal, A. L. Cunningham, O. Godeaux, R. Chlibek, J. Diez-domingo et al., Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults, N Engl J Med, vol.372, issue.22, pp.2087-96, 2015.

, Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older

A. L. Cunningham, H. Lal, M. Kovac, R. Chlibek, S. J. Hwang et al., N Engl J Med, vol.375, issue.11, pp.1019-1051, 2016.

, Adjuvant system AS01: helping to overcome the challenges of modern vaccines

A. M. Didierlaurent, B. Laupèze, D. Pasquale, A. Hergli, N. Collignon et al., Expert Rev Vaccines, vol.16, pp.55-63, 2017.

M. Coccia, C. Collignon, C. Hervé, A. Chalon, I. Welsby et al., Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFN? response promoting vaccine immunogenicity, vol.2, p.25, 2017.

, Reported vaccine-preventable diseases--United States, 1993, and the childhood immunization initiative, Centers for Disease Control and Prevention (CDC). MMWR Morb Mortal Wkly Rep, vol.43, issue.4, pp.57-60, 1994.

B. Systems-vaccinology.-pulendran, L. S. Nakaya, and H. I. Immunity, , vol.33, pp.516-545, 2010.

, Computational systems biology. Kitano H. Nature, vol.420, pp.206-216, 2002.

, Systems biology approaches to new vaccine development

P. Kennedy, I. G. Li, and . Ovsyannikova, Curr Opin Immunol, vol.23, issue.3, pp.436-443, 2011.

, The model organism as a system: integrating 'omics' data sets, Nat Rev Mol Cell Biol, vol.7, issue.3, pp.198-210, 2006.

, ChIPing away at the genome: the new frontier travel guide, Aleksic J, Russell S. Mol Biosyst, vol.5, issue.12, pp.1421-1429, 2009.

G. A. Poland, I. G. Ovsyannikova, and R. M. Jacobson, Application of pharmacogenomics to vaccines, Pharmacogenomics, vol.10, issue.5, pp.837-52, 2009.

, Statistical design of quantitative mass spectrometry-based proteomic experiments. Oberg AL, Vitek O, J Proteome Res, vol.8, issue.5, pp.2144-56, 2009.

J. T. Leek, R. B. Scharpf, H. C. Bravo, D. Simcha, B. Langmead et al., Tackling the widespread and critical impact of batch effects in high-throughput data, Nat Rev Genet, vol.11, issue.10, pp.733-742, 2010.

J. Subramanian and R. Simon, Gene expression-based prognostic signatures in lung cancer: ready for clinical use?, J Natl Cancer Inst, vol.102, issue.7, pp.464-74, 2010.

G. Thomas, K. B. Jacobs, P. Kraft, M. Yeager, S. Wacholder et al., A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1), Nat Genet, vol.41, issue.5, pp.579-84, 2009.

, Covariance-regularized regression and classification for high-dimensional problems

D. M. Witten, R. Tibshirani, and . J-r, Stat Soc Series B Stat Methodol, vol.71, issue.3, pp.615-636, 2009.

L. Shi, G. Campbell, W. D. Jones, F. Campagne, Z. Wen et al., The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models, Nat Biotechnol, vol.28, issue.8, pp.827-865, 2010.

, Covariance-regularized regression and classification for high-dimensional problems

D. M. Witten, R. Tibshirani, and . J-r, Stat Soc Series B Stat Methodol, vol.71, issue.3, pp.615-636, 2009.

J. Subramanian and R. Simon, What should physicians look for in evaluating prognostic gene-expression signatures?, Nat Rev Clin Oncol, vol.7, issue.6, pp.327-361, 2010.

, Prognosis and prognostic research: validating a prognostic model, BMJ, vol.338, p.605, 2009.

J. Frelinger, J. Ottinger, C. Gouttefangeas, and C. Chan, Modeling flow cytometry data for cancer vaccine immune monitoring, Cancer Immunol Immunother, vol.59, issue.9, pp.1435-1476, 2010.

, ChIPing away at the genome: the new frontier travel guide, Aleksic J, Russell S. Mol Biosyst, vol.5, issue.12, pp.1421-1429, 2009.

, Bioinformatics analysis of Brucella vaccines and vaccine targets using VIOLIN. He Y, Xiang Z. Immunome Res, vol.6, p.5, 2010.

, Bioinformatics in new generation flavivirus vaccines. Koraka P, Martina BE, Osterhaus AD, J Biomed Biotechnol, p.864029, 2010.

E. Heinz, P. Tischler, T. Rattei, G. Myers, M. Wagner et al., Comprehensive in silico prediction and analysis of chlamydial outer membrane proteins reflects evolution and life style of the Chlamydiae, pDOCK: a new technique for rapid and accurate docking of peptide ligands to Major Histocompatibility Complexes. Khan JM, Ranganathan S. Immunome Res, vol.10, p.2, 2009.

, Immunogenicity of novel Dengue virus epitopes identified by bioinformatic analysis

G. Sánchez-burgos, J. Ramos-castañeda, R. Cedillo-rivera, and E. Dumonteil, Virus Res, vol.153, issue.1, pp.113-133, 2010.

M. V. Larsen, A. Lelic, R. Parsons, M. Nielsen, I. Hoof et al., Identification of CD8+ T cell epitopes in the West Nile virus polyprotein by reverseimmunology using NetCTL, PLoS One, vol.5, issue.9, p.12697, 2010.

, Allele dynamics plots for the study of evolutionary dynamics in viral populations. Steinbrück L, McHardy AC, Nucleic Acids Res, vol.39, issue.1, p.4, 2011.

Y. L. Chong, A. Padhi, P. J. Hudson, and P. M. Plos-pathog, The effect of vaccination on the evolution and population dynamics of avian paramyxovirus-1, 2010.

A. Wang, S. C. Johnston, J. Chou, D. Dean, and . Bacteriol, A systemic network for Chlamydia pneumoniae entry into human cells, vol.192, pp.2809-2824, 2010.

X. Guo, Y. Xu, G. Bian, A. D. Pike, Y. Xie et al., Response of the mosquito protein interaction network to dengue infection, vol.11, p.380, 2010.

T. D. Querec, R. S. Akondy, E. K. Lee, W. Cao, H. I. Nakaya et al., Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans, Nat Immunol, vol.10, issue.1, pp.116-125, 2009.

Y. Kumagai and S. Akira, Identification and functions of pattern-recognition receptors, J Allergy Clin Immunol, vol.125, issue.5, pp.985-92, 2010.

M. Jan, S. Meng, N. C. Chen, J. Mai, H. Wang et al., Inflammatory and autoimmune reactions in atherosclerosis and vaccine design informatics, p.459798, 2010.

, New paradigms for generating effective CD8+ T cell responses against HIV-1/AIDS. Ahlers JD, Belyakov IM, vol.9, pp.528-565, 2010.

T. M. Love, S. W. Thurston, M. C. Keefer, S. Dewhurst, H. Y. Lee et al., Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ Tlymphocyte responses exert strong selective pressure in simian immunodeficiency virusinfected macaques but still fail to clear founder epitope sequences, vol.84, pp.5802-5816, 2010.

S. Kaewpongsri, C. Sukasem, C. Srichunrusami, E. Pasomsub, J. Zwang et al., An integrated bioinformatics approach to the characterization of influenza A/H5N1 viral sequences by microarray data: Implication for monitoring H5N1 emerging strains and designing appropriate influenza vaccines, Mol Cell Probes, vol.24, issue.6, pp.387-95, 2010.

C. M. Romano, I. M. De-carvalho-mello, L. F. Jamal, F. L. De-melo, A. Iamarino et al., Social networks shape the transmission dynamics of hepatitis C virus, PLoS One, vol.5, issue.6, p.11170, 2010.

, Dynamics and control of diseases in networks with community structure. Salathé M, Jones JH, vol.6, p.1000736, 2010.

F. Pappalrado, P. Zhang, M. Halling-brown, K. Basford, A. Scalia et al., Computational Simulations of the Immune systems for personalized medicine: State of the art and challenges, Current Pharmacogenomics and Personalized Medicine, vol.6, pp.260-271, 2008.

, Immunoinformatics and systems biology methods for personalized medicine, Yan Q. Methods Mol Biol, vol.662, pp.203-223, 2010.

G. A. Poland, I. G. Ovsyannikova, R. M. Jacobson, R. A. Vierkant, S. J. Jacobsen et al., Identification of an association between HLA class II alleles and low antibody levels after measles immunization, vol.20, pp.430-438, 2001.

B. A. Mckinney, D. M. Reif, M. T. Rock, K. M. Edwards, S. F. Kingsmore et al., Cytokine expression patterns associated with systemic adverse events following smallpox immunization, J Infect Dis, vol.194, issue.4, pp.444-53, 2006.

, Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology. Pulendran B, Nat Rev Immunol, vol.9, issue.10, pp.741-748, 2009.

D. Gaucher, R. Therrien, N. Kettaf, B. R. Angermann, G. Boucher et al., Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses, J Exp Med, vol.205, issue.13, pp.3119-3150, 2008.

J. M. Zahradnik, R. B. Couch, and J. L. Gerin, Safety and immunogenicity of a purified hepatitis B virus vaccine prepared by using recombinant DNA technology, J Infect Dis, 1987.

D. R. Lowy and J. T. Schiller, Prophylactic human papillomavirus vaccines, J Clin Invest, vol.116, issue.5, pp.1167-73, 2006.

I. G. Ovsyannikova, K. L. Johnson, . Bergen-hr-3rd, and G. A. Poland, Mass spectrometry and peptide-based vaccine development, Clin Pharmacol Ther, vol.82, issue.6, pp.644-52, 2007.

R. M. Jacobson, R. A. Vierkant, V. S. Pankratz, G. A. Poland, and . Vaccine, HLA supertypes and immune responses to measles-mumps-rubella viral vaccine: findings and implications for vaccine design, Ovsyannikova IG, vol.25, issue.16, pp.3090-100, 2007.

A. Grignolio, M. Mishto, A. M. Faria, P. Garagnani, C. Franceschi et al., Towards a liquid self: how time, geography, and life experiences reshape the biological identity, P Front Immunol, vol.5, p.153, 2014.

, Immunobiography and the Heterogeneity of Immune Responses in the Elderly: A Focus on Inflammaging and Trained Immunity

D. Frasca, A. Diaz, M. Romero, F. Ferracci, and B. B. Blomberg, MicroRNAs miR-155 and miR-16 Decrease AID and E47 in B Cells from Elderly Individuals, J Immunol, vol.195, issue.5, pp.2134-2174, 2015.

, Trained Immunity: An Ancient Way of Remembering. Netea MG, van der Meer JW Cell Host Microbe, vol.21, pp.297-300, 2017.

. Systemic-acquired-resistance, J. A. Ryals, U. H. Neuenschwander, M. G. Willits, A. Molina et al., Plant Cell, vol.8, issue.10, pp.1809-1819, 1996.

, Systemic acquired resistance. Durrant WE, Dong X, Annu Rev Phytopathol, vol.42, pp.185-209, 2004.

P. Schmid-hempel and D. Ebert, Evolutionary parasitology: the integrated study of infections, immunology. Ecology and Genetics, 2013.

B. Milutinovi?, R. Peuß, K. Ferro, and J. Kurtz, Zoology (Jena), Immune priming in arthropods: an update focusing on the red flour beetle, vol.119, pp.254-61, 2016.

G. Tettamanti, A. Grimaldi, R. Ferrarese, M. Palazzi, G. Perletti et al., Leech responses to tissue transplantation, Tissue Cell, vol.35, issue.3, pp.199-212, 2003.

, Specific memory within innate immune systems, Kurtz J. Trends Immunol, 2005.

M. G. Netea, J. Quintin, and J. W. Van-der-meer, Trained immunity: a memory for innate host defense, Cell Host Microbe, vol.9, issue.5, pp.355-61, 2011.

M. G. Netea, L. A. Joosten, E. Latz, K. H. Mills, G. Natoli et al., A program of innate immune memory in health and disease, vol.352, p.1098, 2016.

, Effect of Bacillus Callmette Guerin (BCG) on the receptivity of nude mice to Schistosoma mansoni

J. Tribouley, J. Tribouley-duret, M. Appriou, and . C-r, Seances Soc Biol Fil, vol.172, issue.5, pp.902-906, 1978.

, The role of BCG/PPD-activated macrophages in resistance against systemic candidiasis in mice. van 't Wout JW, Poell R, van Furth R, Scand J Immunol, vol.36, issue.5, pp.713-722, 1992.

F. Bistoni, G. Verducci, S. Perito, A. Vecchiarelli, P. Puccetti et al., Immunomodulation by a low-virulence, agerminative variant of Candida albicans. Further evidence for macrophage activation as one of the effector mechanisms of nonspecific anti-infectious protection, J Med Vet Mycol, vol.26, issue.5, pp.285-99, 1988.

, Repeated administration of synthetic oligodeoxynucleotides expressing CpG motifs provides long-term protection against bacterial infection. Klinman DM, Infect Immun, vol.67, issue.11, pp.5658-63, 1999.

M. L. Mbow, D. Gregorio, E. Valiante, N. M. Rappuoli, and R. , New adjuvants for human vaccines, Curr Opin Immunol, vol.22, issue.3, pp.411-417, 2010.

, No one is naive: the significance of heterologous T-cell immunity. Welsh RM, Selin LK, Nat Rev Immunol, vol.2, issue.6, pp.417-443, 2002.

C. S. Benn, M. G. Netea, L. K. Selin, and P. Aaby, A small jab -a big effect: nonspecific immunomodulation by vaccines, Trends Immunol, vol.34, issue.9, pp.431-440, 2013.

P. Aaby, T. R. Kollmann, and C. S. Benn, Nonspecific effects of neonatal and infant vaccination: public-health, immunological and conceptual challenges, Nat Immunol, vol.15, issue.10, pp.895-904, 2014.

E. Töpfer, D. Boraschi, and P. Italiani, Innate Immune Memory: The Latest Frontier of Adjuvanticity, J Immunol Res, p.478408, 2015.

J. Quintin, S. Saeed, J. Martens, E. J. Giamarellos-bourboulis, D. C. Ifrim et al., Candida albicans infection affords protection against reinfection via functional reprogramming of monocytes, Cell Host Microbe, vol.12, issue.2, pp.223-255, 2012.

Y. Dou, B. Fu, R. Sun, W. Li, W. Hu et al., Influenza vaccine induces intracellular immune memory of human NK cells, PLoS One, vol.10, issue.3, p.121258, 2015.

A. Takeuchi, T. Dejima, H. Yamada, K. Shibata, R. Nakamura et al., IL-17 production by ?? T cells is important for the antitumor effect of Mycobacterium bovis bacillus Calmette-Guérin treatment against bladder cancer, Eur J Immunol, vol.41, issue.1, pp.246-51, 2011.

D. W. Fowler, J. Copier, N. Wilson, and A. G. Dalgleish, Mycobacteria activate ?? T-cell anti-tumour responses via cytokines from type 1 myeloid dendritic cells: a mechanism of action for cancer immunotherapy, Cancer Immunol Immunother, 2012.

S. Saeed, J. Quintin, H. H. Kerstens, N. A. Rao, A. Aghajanirefah et al., Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity, vol.345, p.1251086, 2014.

S. C. Cheng, J. Quintin, R. A. Cramer, K. M. Shepardson, S. Saeed et al., HIF-1?-mediated aerobic glycolysis as metabolic basis for trained immunity, vol.345, p.1250684, 2014.

, The epigenetic machinery controlling transgenerational systemic acquired resistance. Luna E, Ton J. Plant Signal Behav, vol.7, pp.615-623, 2012.

, Immunometabolic circuits in trained immunity. Arts RJ, vol.28, issue.5, pp.425-430, 2016.

T. F. Liu, V. T. Vachharajani, B. K. Yoza, and C. E. Mccall, NAD+-dependent sirtuin 1 and 6 proteins coordinate a switch from glucose to fatty acid oxidation during the acute inflammatory response, J Biol Chem, vol.287, issue.31, pp.25758-69, 2012.

T. Latham, L. Mackay, D. Sproul, M. Karim, J. Culley et al., Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression, Nucleic Acids Res, vol.40, issue.11, pp.4794-803, 2012.

J. Kleinnijenhuis, J. Quintin, F. Preijers, L. A. Joosten, D. C. Ifrim et al., Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes, Proc Natl Acad Sci, vol.109, issue.43, pp.17537-17579, 2012.

S. L. Burgess, E. Buonomo, M. Carey, C. Cowardin, C. Naylor et al., Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis, vol.5, p.1817, 2014.

E. Biagi, L. Nylund, M. Candela, R. Ostan, L. Bucci et al., Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians, vol.5, p.10667, 2010.

G. Microbiota, E. Longevity, E. Biagi, C. Franceschi, S. Rampelli et al., Curr Biol, vol.26, issue.11, pp.1480-1485, 2016.

L. Wen, A. Duffy, and . Nutr, Factors Influencing the Gut Microbiota, Inflammation, and Type 2 Diabetes, vol.147, pp.1468-1475, 2017.

H. Schlums, F. Cichocki, B. Tesi, J. Theorell, V. Beziat et al., Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function, vol.42, pp.443-56, 2015.

J. Lee, T. Zhang, I. Hwang, A. Kim, L. Nitschke et al., Epigenetic modification and antibody-dependent expansion of memory-like NK cells in human cytomegalovirus-infected individuals, vol.42, pp.431-473, 2015.

H. Schlums, F. Cichocki, B. Tesi, J. Theorell, V. Beziat et al., Cytomegalovirus infection drives adaptive epigenetic diversification of NK cells with altered signaling and effector function, vol.42, pp.443-56, 2015.

, The epigenetic landscape of age-related diseases: the geroscience perspective

N. Gensous, M. G. Bacalini, C. Pirazzini, E. Marasco, C. Giuliani et al., Biogerontology, vol.18, issue.4, pp.549-559, 2017.

J. Krol, I. Loedige, and W. Filipowicz, The widespread regulation of microRNA biogenesis, function and decay, Nat Rev Genet, vol.11, issue.9, pp.597-610, 2010.

R. M. O'connell, A. A. Chaudhuri, D. S. Rao, and D. Baltimore, Inositol phosphatase SHIP1 is a primary target of miR-155, Proc Natl Acad Sci, vol.106, issue.17, pp.7113-7121, 2009.

F. Olivieri, M. C. Albertini, M. Orciani, A. Ceka, M. Cricca et al., DNA damage response (DDR) and senescence: shuttled inflamma-miRNAs on the stage of inflamm-aging, Oncotarget, vol.6, issue.34, pp.35509-35530, 2015.

D. Frasca, A. Diaz, M. Romero, F. Ferracci, and B. B. Blomberg, MicroRNAs miR-155 and miR-16 Decrease AID and E47 in B Cells from Elderly Individuals, J Immunol, vol.195, issue.5, pp.2134-2174, 2015.

T. Fulop, G. Dupuis, S. Baehl, L. Page, A. Bourgade et al., From inflamm-aging to immune-paralysis: a slippery slope during aging for immuneadaptation, vol.17, pp.147-57, 2016.

A. Christ, S. Bekkering, E. Latz, and N. P. Riksen, Long-term activation of the innate immune system in atherosclerosis, Semin Immunol, vol.28, issue.4, pp.384-93, 2016.

, The cells that mediate innate immune memory and their functional significance in inflammatory and infectious diseases. Gardiner CM, Mills KH, Semin Immunol, 2016.

&. Inflammaging, &. Garb-aging, C. Franceschi, P. Garagnani, G. Vitale et al., Trends Endocrinol Metab, vol.28, issue.3, pp.199-212, 2017.

G. A. Poland, I. G. Ovsyannikova, R. M. Jacobson, and D. I. Smith, Heterogeneity in vaccine immune response: the role of immunogenetics and the emerging field of vaccinomics, vol.82, pp.653-64, 2007.

V. Pharmacology and G. A. Poland, Clin Pharmacol Ther, vol.82, issue.6, pp.623-629, 2007.

, Reverse vaccinology: developing vaccines in the era of genomics. Sette A, Rappuoli R. Immunity, vol.33, pp.530-571, 2010.

. Emerging, Y. He, R. Rappuoli, D. Groot, A. S. Chen et al., J Biomed Biotechnol, p.218590, 2010.

, Rationally designed strings of promiscuous CD4(+) T cell epitopes provide help to Haemophilus influenzae type b oligosaccharide: a model for new conjugate vaccines

F. Falugi, R. Petracca, M. Mariani, E. Luzzi, S. Mancianti et al., Eur J Immunol, vol.31, issue.12, pp.3816-3840, 2001.

E. Assarsson, J. A. Greenbaum, M. Sundström, L. Schaffer, J. A. Hammond et al., Kinetic analysis of a complete poxvirus transcriptome reveals an immediate-early class of genes, Proc Natl Acad Sci, vol.105, issue.6, pp.2140-2145, 2008.

G. A. Poland, I. G. Ovsyannikova, R. M. Jacobson, and D. I. Smith, Heterogeneity in vaccine immune response: the role of immunogenetics and the emerging field of vaccinomics, vol.82, pp.653-64, 2007.

G. A. Poland, I. G. Ovsyannikova, and R. M. Jacobson, Application of pharmacogenomics to vaccines, Pharmacogenomics, vol.10, issue.5, pp.837-52, 2009.

. The, J. Klein, A. Sato, J. Engl, and . Med, First of two parts, vol.343, pp.702-711, 2000.

, Polymorphism in clinical immunology -From HLA typing to immunogenetic profiling

P. Jin and E. Wang, J Transl Med, vol.18, issue.1, p.8, 2003.

D. Burgner, S. E. Jamieson, and J. M. Blackwell, Genetic susceptibility to infectious diseases: big is beautiful, but will bigger be even better?, Lancet Infect Dis, vol.6, issue.10, pp.653-63, 2006.

, Response to hepatitis B vaccine: multiple HLA genes are involved. Desombere I, Willems A, Leroux-Roels G. Tissue Antigens, vol.51, pp.593-604, 1998.

, Identification of an association between HLA class II alleles and low antibody levels after measles immunization

G. A. Poland, I. G. Ovsyannikova, R. M. Jacobson, R. A. Vierkant, S. J. Jacobsen et al., , vol.20, pp.430-438, 2001.

C. Wang, J. Tang, W. Song, E. Lobashevsky, C. M. Wilson et al., HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination, vol.39, pp.978-88, 2004.

, Class II HLA alleles and hepatitis B virus persistence in African Americans

C. L. Thio, M. Carrington, D. Marti, S. J. O'brien, D. Vlahov et al., J Infect Dis, vol.179, issue.4, pp.1004-1010, 1999.

, Pros and cons of genetic association studies in hepatitis B. Thursz M. Hepatology, vol.40, pp.284-290, 2004.

I. G. Ovsyannikova, R. M. Jacobson, R. A. Vierkant, S. Pankratz, V. Jacobsen et al., Associations between human leukocyte antigen (HLA) alleles and very high levels of measles antibody following vaccination, vol.22, pp.1914-1934, 2004.

I. G. Ovsyannikova, R. M. Jacobson, N. Dhiman, R. A. Vierkant, V. S. Pankratz et al., Human leukocyte antigen and cytokine receptor gene polymorphisms associated with heterogeneous immune responses to mumps viral vaccine, Pediatrics, vol.121, issue.5, pp.1091-1100, 2008.

I. G. Ovsyannikova, V. S. Pankratz, R. A. Vierkant, R. M. Jacobson, and G. A. Poland, Human leukocyte antigen haplotypes in the genetic control of immune response to measles-mumps-rubella vaccine, J Infect Dis, vol.193, issue.5, pp.655-63, 2006.

R. M. Jacobson, R. A. Vierkant, V. S. Pankratz, G. A. Poland, and . Vaccine, HLA supertypes and immune responses to measles-mumps-rubella viral vaccine: findings and implications for vaccine design, Ovsyannikova IG, vol.25, issue.16, pp.3090-100, 2007.

K. L. Johnson, I. G. Ovsyannikova, G. A. Poland, and D. C. Muddiman, Identification of class II HLA-DRB1*03-bound measles virus peptides by 2D-liquid chromatography tandem mass spectrometry, J Proteome Res, vol.4, issue.6, pp.2243-2252, 2005.

I. G. Ovsyannikova, K. L. Johnson, D. C. Muddiman, R. A. Vierkant, G. A. Poland et al., Identification and characterization of novel, naturally processed measles virus class II HLA-DRB1 peptides, vol.78, pp.42-51, 2004.

M. O. Ota, Z. Ndhlovu, S. Oh, S. Piyasirisilp, J. A. Berzofsky et al., Hemagglutinin protein is a primary target of the measles virus-specific HLA-A2-restricted CD8+ T cell response during measles and after vaccination, J Infect Dis, vol.195, issue.12, pp.1799-807, 2007.

, Epitope-based vaccines: an update on epitope identification, vaccine design and delivery. Sette A, Fikes J, Curr Opin Immunol, vol.15, issue.4, pp.461-70, 2003.

. Ab, H. H. Bui, B. Peters, E. Assarsson, I. Mbawuike et al., Proc Natl Acad Sci, 2007.

A. Deshpande, C. M. Wheeler, W. C. Hunt, C. L. Peyton, P. S. White et al., Variation in HLA class I antigen-processing genes and susceptibility to human papillomavirus type 16-associated cervical cancer, J Infect Dis, vol.197, issue.3, pp.371-81, 2008.

T. Tap1, H. Gostout, B. S. Poland, G. A. Calhoun, E. S. Sohni et al., alleles are predictors of cervical cancer risk, Gynecol Oncol, vol.88, issue.3, pp.326-358, 2003.

S. Shrestha, C. Wang, B. Aissani, C. M. Wilson, J. Tang et al., Interleukin-10 gene (IL10) polymorphisms and human papillomavirus clearance among immunosuppressed adolescents, Cancer Epidemiol Biomarkers Prev, vol.16, issue.8, pp.1626-1658, 2007.

A. Collins, C. Lonjou, and N. E. Morton, Genetic epidemiology of single-nucleotide polymorphisms, Proc Natl Acad Sci, vol.96, issue.26, pp.15173-15180, 1999.

R. Sachidanandam, D. Weissman, S. C. Schmidt, J. M. Kakol, L. D. Stein et al., A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms, International SNP Map Working Group. Nature, vol.409, issue.6822, pp.928-961, 2001.

F. S. Collins and V. J. Mckusick, Implications of the Human Genome Project for medical science, vol.285, pp.540-544, 2001.

T. Therapeutics, . Spielberg, and . Sp, Curr Opin Pediatr, vol.10, issue.2, pp.201-203, 1998.

, Cytokine gene polymorphisms in multifactorial diseases: gateways to novel targets for immunotherapy? Vandenbroeck K, Goris A, Trends Pharmacol Sci, vol.24, issue.6, pp.284-293, 2003.

, Polymorphism in clinical immunology -From HLA typing to immunogenetic profiling

P. Jin and E. Wang, J Transl Med, vol.18, issue.1, p.8, 2003.

, HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination

C. Wang, J. Tang, W. Song, E. Lobashevsky, C. M. Wilson et al., , vol.39, pp.978-88, 2004.

M. J. Kim, A. N. Nafziger, C. D. Harro, H. L. Keyserling, K. M. Ramsey et al., Revaccination of healthy nonresponders with hepatitis B vaccine and prediction of seroprotection response, vol.21, pp.1174-1183, 2003.

H. G. Lee, J. S. Lim, K. Y. Lee, Y. K. Choi, I. S. Choe et al., Peptide-specific CTL induction in HBV-seropositive PBMC by stimulation with peptides in vitro: novel epitopes identified from chronic carriers, Virus Res, vol.50, issue.2, pp.185-94, 1997.

N. Dhiman, G. A. Poland, J. M. Cunningham, R. M. Jacobson, I. G. Ovsyannikova et al., Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors, vol.120, pp.666-72, 2007.

M. Dean, M. Carrington, O. 'brien, and S. J. , Balanced polymorphism selected by genetic versus infectious human disease, Annu Rev Genomics Hum Genet, vol.3, pp.263-92, 2002.

, The shape of things to come. Fitzgerald KA, Golenbock DT. Science, Immunology, vol.316, issue.5831, pp.1574-1580, 2007.

V. Mata-haro, C. Cekic, M. Martin, P. M. Chilton, C. R. Casella et al., The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4, Science, vol.316, issue.5831, pp.1628-1660, 2007.

N. Dhiman, I. G. Ovsyannikova, R. A. Vierkant, J. E. Ryan, V. S. Pankratz et al., Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results, vol.26, pp.1731-1737, 2008.

L. P. Perera, T. A. Waldmann, J. D. Mosca, N. Baldwin, J. A. Berzofsky et al., Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice, vol.81, pp.8774-83, 2007.

, The extent and analysis of cytokine and cytokine receptor gene polymorphism. Keen LJ, Transpl Immunol, vol.10, issue.2-3, pp.143-149, 2002.

, Standards for child and adolescent immunization practices. National Vaccine Advisory Committee. National Vaccine Advisory Committee, Pediatrics, vol.112, issue.4, pp.958-63, 2003.

J. Wallinga, J. C. Heijne, and M. Kretzschmar, A measles epidemic threshold in a highly vaccinated population, PLoS Med, vol.2, issue.11, p.316, 2005.

, Declining population immunity to mumps among Israeli military recruits

M. Huerta, N. Davidovitch, Y. Aboudy, O. E. Ankol, R. D. Balicer et al., , vol.24, pp.6300-6303, 2006.

M. Marin, D. Güris, S. S. Chaves, S. Schmid, and J. F. Seward, Advisory Committee on Immunization Practices, Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP), vol.56, pp.1-40, 2007.

G. R. Siber, M. Santosham, G. R. Reid, C. Thompson, J. Almeido-hill et al., Impaired antibody response to Haemophilus influenzae type b polysaccharide and low IgG2 and IgG4 concentrations in Apache children, N Engl J Med, vol.323, issue.20, pp.1387-92, 1990.

, Prevention of Haemophilus influenzae type b infections in Apache and Navajo children

M. Santosham, B. Rivin, M. Wolff, R. Reid, W. Newcomer et al., J Infect Dis, vol.165, pp.144-51, 1992.

G. A. Poland, Pharmacology, vaccinomics, and the 2nd golden age of vaccinology, Clin Pharmacol Ther, vol.82, issue.6, pp.623-629, 2007.