Human lymph node immune dynamics as driver of vaccine efficacy: an understudied aspect of immune responses

References

• Roush SW. Vaccine-Preventable Disease Table Working G. Historical comparisons of morbidity and mortality for vaccine-preventable diseases in the United States. JAMA. 2007 Nov 14;298(18):2155–2163.
   PubMed Web of Science ®Google Scholar
• Wiedermann U, Garner-Spitzer E, Wagner A. Primary vaccine failure to routine vaccines: why and what to do? Hum Vaccin Immunother. 2016;12(1):239–243.
   PubMed Web of Science ®Google Scholar
• Plotkin SA. Updates on immunologic correlates of vaccine-induced protection. Vaccine. 2020 Feb 24;38(9):2250–2257.
   PubMed Web of Science ®Google Scholar
• Tsang JS, Schwartzberg PL, Kotliarov Y, et al. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell. 2014 Apr 10;157(2):499–513.
   PubMed Web of Science ®Google Scholar
• Kotliarov Y, Sparks R, Martins AJ, et al. Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus. Nat Med. 2020 Apr;26(4):618–629.
   PubMed Web of Science ®Google Scholar
• Blum KS, Pabst R. Lymphocyte numbers and subsets in the human blood. Do they mirror the situation in all organs? Immunol Lett. 2007 Jan 15;108(1):45–51.
   PubMed Web of Science ®Google Scholar
• Havenar-Daughton C, Carnathan DG, Torrents de la Pena A, et al. Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer. Cell Rep. 2016 Nov 22;17(9):2195–2209.
   PubMed Web of Science ®Google Scholar
• Tas JM, Mesin L, Pasqual G, et al. Visualizing antibody affinity maturation in germinal centers. Science. 2016 Mar 4;351(6277):1048–1054.
   PubMed Web of Science ®Google Scholar
• Amodio D, Cotugno N, Macchiarulo G, et al. Quantitative Multiplexed Imaging Analysis Reveals a Strong Association between Immunogen-Specific B Cell Responses and Tonsillar Germinal Center Immune Dynamics in Children after Influenza Vaccination. J Immunol. 2018 Jan 15;200(2):538–550.
   PubMed Web of Science ®Google Scholar
• Moysi E, Pallikkuth S, De Armas LR, et al. Altered immune cell follicular dynamics in HIV infection following influenza vaccination. J Clin Invest. 2018 Jul 2;128(7):3171–3185.
   PubMed Web of Science ®Google Scholar
• Hey-Nguyen WJ, Xu Y, Pearson CF, et al. Quantification of Residual Germinal Center Activity and HIV-1 DNA and RNA Levels Using Fine Needle Biopsies of Lymph Nodes During Antiretroviral Therapy. AIDS Res Hum Retroviruses. 2017 Jul;33(7):648–657.
   PubMed Web of Science ®Google Scholar
• Noe A, Cargill TN, Nielsen CM, et al. The Application of Single-Cell RNA Sequencing in Vaccinology. J Immunol Res. 2020;2020:8624963.
   PubMed Web of Science ®Google Scholar
• Moysi E, Del Rio Estrada PM, Torres-Ruiz F, et al. In Situ Characterization of Human Lymphoid Tissue Immune Cells by Multispectral Confocal Imaging and Quantitative Image Analysis; Implications for HIV Reservoir Characterization. Front Immunol. 2021;12:683396.
   PubMed Web of Science ®Google Scholar
• Neumann EK, Djambazova KV, Caprioli RM, et al. Multimodal Imaging Mass Spectrometry: next Generation Molecular Mapping in Biology and Medicine. J Am Soc Mass Spectrom. 2020 Dec 2;31(12):2401–2415.
   PubMed Web of Science ®Google Scholar
• Wang F, Flanagan J, Su N, et al. RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J Mol Diagn. 2012 Jan;14(1):22–29.
   PubMed Web of Science ®Google Scholar
• Moffitt JR, Hao J, Wang G, et al. High-throughput single-cell gene-expression profiling with multiplexed error-robust fluorescence in situ hybridization. Proc Natl Acad Sci U S A. 2016 Sep 27;113(39):11046–11051.
   PubMed Web of Science ®Google Scholar
• Reeves PM, Sluder AE, Paul SR, et al. Application and utility of mass cytometry in vaccine development. FASEB J. 2018 Jan;32(1):5–15.
   PubMed Web of Science ®Google Scholar
• Qatarneh SM, Kiricuta IC, Brahme A, et al. Three-dimensional atlas of lymph node topography based on the visible human data set. Anat Rec B New Anat. 2006 May;289(3):98–111.
   PubMedGoogle Scholar
• Luscieti P, Hubschmid T, Cottier H, et al. Human lymph node morphology as a function of age and site. J Clin Pathol. 1980 May;33(5):454–461.
   PubMed Web of Science ®Google Scholar
• Jalkanen S, Salmi M. Lymphatic endothelial cells of the lymph node. Nat Rev Immunol. 2020 Feb 24;20(9):566–578.
   PubMed Web of Science ®Google Scholar
• Vono M, Lin A, Norrby-Teglund A, et al. Neutrophils acquire the capacity for antigen presentation to memory CD4(+) T cells in vitro and ex vivo. Blood. 2017 Apr 6;129(14):1991–2001.
   PubMed Web of Science ®Google Scholar
• Takashima A, Yao Y. Neutrophil plasticity: acquisition of phenotype and functionality of antigen-presenting cell. J Leukoc Biol. 2015 Oct;98(4):489–496.
   PubMed Web of Science ®Google Scholar
• Lin A, Lore K. Granulocytes: new Members of the Antigen-Presenting Cell Family. Front Immunol. 2017;8:1781.
   PubMed Web of Science ®Google Scholar
• Liang F, Lindgren G, Sandgren KJ, et al. Vaccine priming is restricted to draining lymph nodes and controlled by adjuvant-mediated antigen uptake. Sci Transl Med. 2017 Jun 7;9(393). https://doi.org/10.1126/scitranslmed.aal2094.
   Web of Science ®Google Scholar
• Mesin L, Ersching J, Victora GD. Germinal Center B Cell Dynamics. Immunity. 2016 Sep 20;45(3):471–482.
   PubMed Web of Science ®Google Scholar
• Ersching J, Efeyan A, Mesin L, et al. Germinal Center Selection and Affinity Maturation Require Dynamic Regulation of mTORC1 Kinase. Immunity. 2017 Jun 20;46(6):1045–1058 e6.
   PubMed Web of Science ®Google Scholar
• Kranich J, Krautler NJ. How Follicular Dendritic Cells Shape the B-Cell Antigenome. Front Immunol. 2016;7:225.
   PubMed Web of Science ®Google Scholar
• de Vinuesa CG, Cook MC, Ball J, et al. Germinal centers without T cells. J Exp Med. 2000 Feb 7;191(3):485–494.
   PubMed Web of Science ®Google Scholar
• Helmold Hait S, Vargas-Inchaustegui DA, Musich T, et al. Early T Follicular Helper Cell Responses and Germinal Center Reactions Are Associated with Viremia Control in Immunized Rhesus Macaques. J Virol. 2019 Feb 15;93(4). DOI:https://doi.org/10.1128/JVI.01687-18.
   Google Scholar
• Kil LP, Vaneman J, van der Lubbe JEM, et al. Restrained expansion of the recall germinal center response as biomarker of protection for influenza vaccination in mice. PLoS One. 2019;14(11):e0225063.
   PubMed Web of Science ®Google Scholar
• Paris RM, Milagres LG, Moysi E, et al. Lower Baseline Germinal Center Activity and Preserved Th1 Immunity are Associated with Hepatitis B Vaccine Response in Treated HIV Infection [Human immunodeficiency virus; AIDS; hepatitis B vaccine; T cell; antibodies]. Pathogens and Immunity. 2017 2017-03-14.;2(1):66–88.
   PubMedGoogle Scholar
• Crotty S. Follicular Helper CD4 T Cells (T FH). Annu Rev Immunol. 2011;29(1):621–663.
   PubMed Web of Science ®Google Scholar
• Karnowski A, Chevrier S, Belz GT, et al. B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1. J Exp Med. 2012 Oct 22;209(11):2049–2064.
   PubMed Web of Science ®Google Scholar
• Weinstein JS, Herman EI, Lainez B, et al. TFH cells progressively differentiate to regulate the germinal center response. Nat Immunol. 2016 Oct;17(10):1197–1205.
   PubMed Web of Science ®Google Scholar
• Song W, Craft J. T follicular helper cell heterogeneity: time, space, and function. Immunol Rev. 2019 Mar;288(1):85–96.
   PubMed Web of Science ®Google Scholar
• Schmitt N, Bentebibel SE, Ueno H. Phenotype and functions of memory Tfh cells in human blood. Trends Immunol. 2014 Sep;35(9):436–442.
   PubMed Web of Science ®Google Scholar
• Verma A, Schmidt BA, Elizaldi SR, et al. Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques. J Virol. 2020 Feb 28;94(6). https://doi.org/10.1128/JVI.01737-19.
   Google Scholar
• Havenar-Daughton C, Lindqvist M, Heit A, et al. CXCL13 is a plasma biomarker of germinal center activity. Proc Natl Acad Sci U S A. 2016 Mar 8;113(10):2702–2707.
   PubMed Web of Science ®Google Scholar
• Bentebibel SE, Lopez S, Obermoser G, et al. Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination. Sci Transl Med. 2013 Mar 13;5(176):176ra32.
   PubMed Web of Science ®Google Scholar
• Boswell KL, Paris R, Boritz E, et al. Loss of circulating CD4 T cells with B cell helper function during chronic HIV infection. PLoS Pathog. 2014 Jan;10(1):e1003853.
   PubMed Web of Science ®Google Scholar
• Poultsidi A, Dimopoulos Y, He TF, et al. Lymph Node Cellular Dynamics in Cancer and HIV: what Can We Learn for the Follicular CD4 (Tfh) Cells? Front Immunol. 2018;9:2233.
   PubMed Web of Science ®Google Scholar
• Poland GA, Kennedy RB, McKinney BA, et al. Vaccinomics, adversomics, and the immune response network theory: individualized vaccinology in the 21st century. Semin Immunol. 2013 Apr;25(2):89– 103.
   PubMed Web of Science ®Google Scholar
• Poyntz HC, Jones A, Jauregui R, et al. Genetic regulation of antibody responsiveness to immunization in substrains of BALB/c mice. Immunol Cell Biol. 2019 Jan;97(1):39–53.
   PubMed Web of Science ®Google Scholar
• Meli AP, Fontes G, Avery DT, et al. The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance. Immunity. 2016 Oct 18;45(4):831–846.
   PubMed Web of Science ®Google Scholar
• Mentzer AJ, O’Connor D, Pollard AJ, et al. Searching for the human genetic factors standing in the way of universally effective vaccines. Philos Trans R Soc Lond B Biol Sci. 2015 Jun 19;370(1671):20140341.
   PubMed Web of Science ®Google Scholar
• Andersson S, Nilsson K, Fagerberg L, et al. The transcriptomic and proteomic landscapes of bone marrow and secondary lymphoid tissues. PLoS One. 2014;9(12):e115911.
   PubMed Web of Science ®Google Scholar
• van de Pavert SA, Olivier BJ, Goverse G, et al. Chemokine CXCL13 is essential for lymph node initiation and is induced by retinoic acid and neuronal stimulation. Nat Immunol. 2009 Nov;10(11):1193–1199.
   PubMed Web of Science ®Google Scholar
• Lian J, Luster AD. Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses. Curr Opin Cell Biol. 2015 Oct;36:1–6.
   PubMed Web of Science ®Google Scholar
• Hennig BJ, Fielding K, Broxholme J, et al. Host genetic factors and vaccine-induced immunity to hepatitis B virus infection. PLoS One. 2008 Mar 26;3(3):e1898.
   PubMed Web of Science ®Google Scholar
• Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010 May;11(5):373–384.
   PubMed Web of Science ®Google Scholar
• Chen J, Liang Z, Lu F, et al. Toll-like receptors and cytokines/cytokine receptors polymorphisms associate with non-response to hepatitis B vaccine. Vaccine. 2011 Jan 17;29(4):706–711.
   PubMed Web of Science ®Google Scholar
• Arav-Boger R, Wojcik GL, Duggal P, et al. Polymorphisms in Toll-like receptor genes influence antibody responses to cytomegalovirus glycoprotein B vaccine. BMC Res Notes. 2012 Mar 13;5(1):140.
   PubMedGoogle Scholar
• Majumder PP, Staats HF, Sarkar-Roy N, et al. Genetic determinants of immune-response to a polysaccharide vaccine for typhoid. Hugo J. 2009 Dec;3(1–4):17–30.
   PubMedGoogle Scholar
• Dhiman N, Ovsyannikova IG, Vierkant RA, et al. Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. Vaccine. 2008 Mar 25;26(14):1731–1736.
   PubMed Web of Science ®Google Scholar
• Randhawa AK, Shey MS, Keyser A, et al. Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants. PLoS Pathog. 2011 Aug;7(8):e1002174.
   PubMed Web of Science ®Google Scholar
• Ma CS, Avery DT, Chan A, et al. Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood. 2012 Apr 26;119(17):3997–4008.
   PubMed Web of Science ®Google Scholar
• Ma CS, Wong N, Rao G, et al. Monogenic mutations differentially affect the quantity and quality of T follicular helper cells in patients with human primary immunodeficiencies. J Allergy Clin Immunol. 2015 Oct;136(4):993–1006 e1.
   PubMed Web of Science ®Google Scholar
• Sasaki S, Sullivan M, Narvaez CF, et al. Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. J Clin Invest. 2011 Aug;121(8):3109–3119.
   PubMed Web of Science ®Google Scholar
• Twy N, Cowling BJ, Gao HZ, et al. Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: a Systematic Review and Meta-analysis. J Infect Dis. 2019 Apr 19;219(10):1525–1535.
   PubMed Web of Science ®Google Scholar
• Linton PJ, Dorshkind K. Age-related changes in lymphocyte development and function. Nat Immunol. 2004 Feb;5(2):133–139.
   PubMed Web of Science ®Google Scholar
• Hadamitzky C, Spohr H, Debertin AS, et al. Age-dependent histoarchitectural changes in human lymph nodes: an underestimated process with clinical relevance? J Anat. 2010 May;216(5):556–562.
   PubMed Web of Science ®Google Scholar
• Thompson HL, Smithey MJ, Surh CD, et al. Functional and Homeostatic Impact of Age-Related Changes in Lymph Node Stroma. Front Immunol. 2017;8:706.
   PubMed Web of Science ®Google Scholar
• Frasca D, Diaz A, Romero M, et al. Age effects on B cells and humoral immunity in humans. Ageing Res Rev. 2011 Jul;10(3):330–335.
   PubMed Web of Science ®Google Scholar
• Linterman MA. How T follicular helper cells and the germinal centre response change with age. Immunol Cell Biol. 2014 Jan;92(1):72–79.
   PubMed Web of Science ®Google Scholar
• Sage PT, Tan CL, Freeman GJ, et al. Defective TFH Cell Function and Increased TFR Cells Contribute to Defective Antibody Production in Aging. Cell Rep. 2015 Jul 14;12(2):163–171.
   PubMed Web of Science ®Google Scholar
• Weng N-P, Akbar AN, Goronzy J. CD28− T cells: their role in the age-associated decline of immune function. Trends Immunol. 2009 Jul;30(7):306–312.
   PubMed Web of Science ®Google Scholar
• Sakata-Kaneko S, Wakatsuki Y, Matsunaga Y, et al. Altered Th1/Th2 commitment in human CD4+ T cells with ageing. Clin Exp Immunol. 2001 May;120(2):267–273.
   Web of Science ®Google Scholar
• *Shankwitz K, Pallikkuth S, Sirupangi T, et al. Compromised steady-state germinal center activity with age in nonhuman primates. Aging Cell. 2020 Feb;19(2):e13087.
   PubMed Web of Science ®Google Scholar
• Aydar Y, Balogh P, Tew JG, et al. Altered Regulation of FcγRII on Aged Follicular Dendritic Cells Correlates with Immunoreceptor Tyrosine-Based Inhibition Motif Signaling in B Cells and Reduced Germinal Center Formation. J Immunol. 2003 Dec 1;171(11):5975–5987.
   PubMed Web of Science ®Google Scholar
• Yang X, Stedra J, Cerny J. Relative contribution of T and B cells to hypermutation and selection of the antibody repertoire in germinal centers of aged mice. J Exp Med. 1996 Mar 1;183(3):959–970.
   PubMed Web of Science ®Google Scholar
• Kolar GR, Mehta D, Wilson PC, et al. Diversity of the Ig repertoire is maintained with age in spite of reduced germinal centre cells in human tonsil lymphoid tissue. Scand J Immunol. 2006 Sep;64(3):314–324.
   PubMed Web of Science ®Google Scholar
• Gensollen T, Iyer SS, Kasper DL, et al. How colonization by microbiota in early life shapes the immune system. Science. 2016 Apr 29;352(6285):539–544.
   PubMed Web of Science ®Google Scholar
• Kraal G, Samsom JN, Mebius RE. The importance of regional lymph nodes for mucosal tolerance. Immunol Rev. 2006 Oct;213(1):119–130.
   PubMedGoogle Scholar
• Zheng D, Liwinski T, Elinav E. Interaction between microbiota and immunity in health and disease. Cell Res. 2020 Jun;30(6):492–506.
   PubMed Web of Science ®Google Scholar
• Gaboriau-Routhiau V, Rakotobe S, Lecuyer E, et al. The key role of segmented filamentous bacteria in the coordinated maturation of gut helper T cell responses. Immunity. 2009 Oct 16;31(4):677–689.
   PubMed Web of Science ®Google Scholar
• Wampach L, Heintz-Buschart A, Fritz JV, et al. Birth mode is associated with earliest strain-conferred gut microbiome functions and immunostimulatory potential. Nat Commun. 2018 Nov 30;9(1):5091.
   PubMedGoogle Scholar
• Nemes E, Lefler E, Szegedi L, et al. Gluten intake interferes with the humoral immune response to recombinant hepatitis B vaccine in patients with celiac disease. Pediatrics. 2008 Jun;121(6):e1570–6.
   PubMed Web of Science ®Google Scholar
• Harris VC, Armah G, Fuentes S, et al. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana. J Infect Dis. 2017 Jan 1;215(1):34–41.
   PubMed Web of Science ®Google Scholar
• Hagan T, Cortese M, Rouphael N, et al. Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans. Cell. 2019 Sep 5;178(6):1313–1328 e13.
   PubMed Web of Science ®Google Scholar
• Reboldi A, Cyster JG. Peyer’s patches: organizing B-cell responses at the intestinal frontier. Immunol Rev. 2016 May;271(1):230–245.
   PubMed Web of Science ®Google Scholar
• Weller S, Faili A, Garcia C, et al. CD40-CD40L independent Ig gene hypermutation suggests a second B cell diversification pathway in humans. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1166–1170.
   PubMed Web of Science ®Google Scholar
• Perruzza L, Gargari G, Proietti M, et al. T Follicular Helper Cells Promote a Beneficial Gut Ecosystem for Host Metabolic Homeostasis by Sensing Microbiota-Derived Extracellular ATP. Cell Rep. 2017 Mar 14;18(11):2566–2575.
   PubMed Web of Science ®Google Scholar
• Barbet G, Sander LE, Geswell M, et al. Sensing Microbial Viability through Bacterial RNA Augments T Follicular Helper Cell and Antibody Responses. Immunity. 2018 Mar 20;48(3):584–598 e5.
   PubMed Web of Science ®Google Scholar
• Williams WB, Liao HX, Moody MA, et al. HIV-1 VACCINES. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science. 2015 Aug 14;349(6249):aab1253.
   PubMed Web of Science ®Google Scholar
• Valdez Y, Brown EM, Finlay BB. Influence of the microbiota on vaccine effectiveness. Trends Immunol. 2014 Nov;35(11):526–537.
   PubMed Web of Science ®Google Scholar
• Moir S, Fauci AS. B-cell responses to HIV infection. Immunol Rev. 2017 Jan;275(1):33–48.
   PubMed Web of Science ®Google Scholar
• Migueles SA, Connors M. Success and failure of the cellular immune response against HIV-1 [Review]. Nat Immunol. 2015;16(6):563–570. 06//print.
   PubMed Web of Science ®Google Scholar
• Collier AC, Corey L, and Murphy, VL, et al. Antibody to human immunodeficiency virus (HIV) and suboptimal response to hepatitis B vaccination. Ann Intern Med. 1988 Jul 15;109(2):101–105.
   PubMed Web of Science ®Google Scholar
• Zeng M, Smith AJ, Wietgrefe SW, et al. Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections. J Clin Invest. 2011 Mar;121(3):998–1008.
   PubMed Web of Science ®Google Scholar
• Perreau M, Savoye AL, De Crignis E, et al. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med. 2013 Jan 14;210(1):143–156.
   PubMed Web of Science ®Google Scholar
• Mueller SN, Germain RN. Stromal cell contributions to the homeostasis and functionality of the immune system. Nat Rev Immunol. 2009 Sep;9(9):618–629.
   PubMed Web of Science ®Google Scholar
• Whitaker JA, Rouphael NG, Edupuganti S, et al. Strategies to increase responsiveness to hepatitis B vaccination in adults with HIV-1. Lancet Infect Dis. 2012 Dec;12(12):966–976.
   PubMed Web of Science ®Google Scholar
• Crum-Cianflone NF, Eberly LE, Duplessis C, et al. Immunogenicity of a monovalent 2009 influenza A (H1N1) vaccine in an immunocompromised population: a prospective study comparing HIV-infected adults with HIV-uninfected adults. Clin Infect Dis. 2011 Jan 1;52(1):138–146.
   PubMed Web of Science ®Google Scholar
• Pallikkuth S, Parmigiani A, Silva SY, et al. Impaired peripheral blood T-follicular helper cell function in HIV-infected nonresponders to the 2009 H1N1/09 vaccine. Blood. 2012 Aug 2;120(5):985–993.
   PubMed Web of Science ®Google Scholar
• Brodin P, Jojic V, Gao T, et al. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1–2):37–47.
   PubMed Web of Science ®Google Scholar
• Merani S, Pawelec G, Kuchel GA, et al. Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection. Front Immunol. 2017;8:784.
   PubMed Web of Science ®Google Scholar
• Furman D, Jojic V, Sharma S, et al. Cytomegalovirus infection enhances the immune response to influenza. Sci Transl Med. 2015 Apr 1;7(281):281ra43.
   PubMed Web of Science ®Google Scholar
• Jergovic M, Uhrlaub JL, Contreras NA, et al. Do cytomegalovirus-specific memory T cells interfere with new immune responses in lymphoid tissues? Geroscience. 2019 Apr;41(2):155–163.
   PubMed Web of Science ®Google Scholar
• Gordon CL, Miron M, Thome JJ, et al. Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. J Exp Med. 2017 Mar 6;214(3):651–667.
   PubMed Web of Science ®Google Scholar
• Clement M, Humphreys IR. Cytokine-Mediated Induction and Regulation of Tissue Damage During Cytomegalovirus Infection. Front Immunol. 2019;10:78.
   PubMed Web of Science ®Google Scholar
• Madore DV, Meade BD, Rubin F, et al. Utilization of serologic assays to support efficacy of vaccines in nonclinical and clinical trials: meeting at the crossroads. Vaccine. 2010 Jun 23;28(29):4539–4547.
   PubMed Web of Science ®Google Scholar
• Nakaya HI, Hagan T, Duraisingham SS, et al. Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures. Immunity. 2015 Dec 15;43(6):1186–1198.
   PubMed Web of Science ®Google Scholar
• Coates EE, Costner PJ, Nason MC, et al. Lymph Node Activation by PET/CT Following Vaccination With Licensed Vaccines for Human Papillomaviruses. Clin Nucl Med. 2017 May;42(5):329–334.
   PubMed Web of Science ®Google Scholar
• Tatovic D, Young P, Kochba E, et al. Fine-Needle Aspiration Biopsy of the Lymph Node: a Novel Tool for the Monitoring of Immune Responses after Skin Antigen Delivery. J Immunol. 2015 Jul 1;195(1):386–392.
   PubMed Web of Science ®Google Scholar
• Yewdell JW, Santos JJS. Original Antigenic Sin: how Original? How Sinful? Cold Spring Harb Perspect Med. 2021 May 3;11(5):a038786.
   PubMed Web of Science ®Google Scholar
• Turner JS, Zhou JQ, Han J, et al. Human germinal centres engage memory and naive B cells after influenza vaccination. Nature. 2020 Oct;586(7827):127–132.
   PubMed Web of Science ®Google Scholar
• Crotty S. T Follicular Helper Cell Biology: a Decade of Discovery and Diseases. Immunity. 2019 May 21;50(5):1132–1148.
   PubMed Web of Science ®Google Scholar
• Padhan K, Moysi E, Noto A, et al. Acquisition of optimal TFH cell function is defined by specific molecular, positional, and TCR dynamic signatures. Proc Natl Acad Sci U S A. 2021 May 4;118(18):e2016855118.
   PubMed Web of Science ®Google Scholar
• Estes JD, Reilly C, Trubey CM, et al. Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy. J Infect Dis. 2015 Mar 1;211(5):744–754.
   PubMed Web of Science ®Google Scholar
• Coccia M, Collignon C, Herve C, et al. Cellular and molecular synergy in AS01-adjuvanted vaccines results in an early IFNgamma response promoting vaccine immunogenicity. NPJ Vaccines. 2017;2(1):25.
   PubMed Web of Science ®Google Scholar
• Lofano G, Mancini F, Salvatore G, et al. Oil-in-Water Emulsion MF59 Increases Germinal Center B Cell Differentiation and Persistence in Response to Vaccination. J Immunol. 2015 Aug 15;195(4):1617–1627.
   PubMed Web of Science ®Google Scholar
• Mastelic Gavillet B, Eberhardt CS, Auderset F, et al. MF59 Mediates Its B Cell Adjuvanticity by Promoting T Follicular Helper Cells and Thus Germinal Center Responses in Adult and Early Life. J Immunol. 2015 May 15;194(10):4836–4845.
   PubMed Web of Science ®Google Scholar
• Morel PA, Turner MS. Designing the optimal vaccine: the importance of cytokines and dendritic cells. Open Vaccine J. 2010;3(1):7–17.
   PubMedGoogle Scholar
• Zhang L, Wang W, Wang S. Effect of vaccine administration modality on immunogenicity and efficacy. Expert Rev Vaccines. 2015;14(11):1509–1523.
   PubMed Web of Science ®Google Scholar
• Maruggi G, Zhang C, Li J, et al. mRNA as a Transformative Technology for Vaccine Development to Control Infectious Diseases. Mol Ther. 2019 Apr 10;27(4):757–772.
   PubMed Web of Science ®Google Scholar
• Tokatlian T, Read BJ, Jones CA, et al. Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers. Science. 2019 Feb 8;363(6427):649–654.
   PubMed Web of Science ®Google Scholar