Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
Open accessAbstract
During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.
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Some age-related B cell deficiencies may occur secondary to T cell deficiencies.
“In view of the critical role played by CD4 + T cells in orchestrating the immune response, some of the age-related deficiencies observed in B cells (51,53,54), which include a reduction in the number of plasmablasts that develop in response to influenza vaccination (55) and the production of poor-quality antibodies to carbohydrate antigens (56)(57)(58), may occur secondary to T cell deficiencies.”
From Causes, consequences, and reversal of immune system aging (2013) · cites this paper as [55]
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An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1994) · doi:10.1201/9780429246593 · Cited by 40,500 · see citing works
A Simple Sequentially Rejective Multiple Test Procedure
(1979) · Scandinavian Journal of Statistics · doi:10.2307/4615733 · Cited by 21,526 · see citing works
An Introduction to the Bootstrap
Efron, B., & Tibshirani, R. J. (1993) · doi:10.1007/978-1-4899-4541-9 · Cited by 21,230 · see citing works
Fiore, A. E., Shay, D. K., Broder, K., Iskander, J. K., Uyeki, T. M., Mootrey, G., Bresee, J. S., & Cox, N. S. (2001) · PsycEXTRA Dataset · doi:10.1037/e548312006-001 · Cited by 5,006 · see citing works
A class of distributions which includes the normal ones
Azzalini, A. (1985) · Padua Research Archive (University of Padova) · Cited by 2,612 · see citing works
Predominant Autoantibody Production by Early Human B Cell Precursors
Wardemann, H., Yurasov, S., Schaefer, A., Young, J. W., Meffre, E., & Nussenzweig, M. C. (2003) · Science · doi:10.1126/science.1086907 · Cited by 2,088 · see citing works
Le, M. (2007) · Medical Entomology and Zoology · Cited by 1,625 · see citing works
Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells
Bernasconi, N. L., Traggiai, E., & Lanzavecchia, A. (2002) · Science · doi:10.1126/science.1076071 · Cited by 1,304 · see citing works
Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Harpaz, R., Ortega‐Sanchez, I. R., & Seward, J. F. (2008) · Cited by 1,302 · see citing works
Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus
Hancock, K., Veguilla, V., Lu, X., Zhong, W., Butler, E. N., Sun, H., Liu, F., Dong, L., DeVos, J. R., Gargiullo, P. M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0906453 · Cited by 1,260 · see citing works
Antibody response to influenza vaccination in the elderly: A quantitative review
GOODWIN, K., VIBOUD, C., & SIMONSEN, L. (2006) · Vaccine · doi:10.1016/j.vaccine.2005.08.105 · Cited by 1,064 · see citing works
Rapid cloning of high-affinity human monoclonal antibodies against influenza virus
Wrammert, J., Smith, K., Miller, J., Langley, W. A., Kokko, K. E., Larsen, C. P., Zheng, N., Mays, I., Garman, L., Helms, C., et al. (2008) · Nature · doi:10.1038/nature06890 · Cited by 1,026 · see citing works
Self-citationThe Efficacy of Influenza Vaccination in Elderly Individuals
Govaert, T. M. E. (1994) · JAMA · doi:10.1001/jama.1994.03520210045030 · Cited by 883 · see citing works
Prevention and Control of Influenza
(1985) · Annals of Internal Medicine · doi:10.7326/0003-4819-103-4-560 · Cited by 809 · see citing works
Wrammert, J., Koutsonanos, D., Li, G., Edupuganti, S., Sui, J., Michael, M., McCausland, M. M., Skountzou, I., Hornig, M., Lipkin, W. I., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20101352 · Cited by 777 · see citing works
Self-citationChemokines and the Tissue-Specific Migration of Lymphocytes
Kunkel, E. J., & Butcher, E. C. (2002) · Immunity · doi:10.1016/s1074-7613(01)00261-8 · Cited by 688 · see citing works
B-cell responses to vaccination at the extremes of age
Siegrist, C.-A., & Aspinall, R. (2009) · Nature Reviews Immunology · doi:10.1038/nri2508 · Cited by 659 · see citing works
The structural relationship: regression in biology
McArdle, B. H. (1988) · Canadian Journal of Zoology · doi:10.1139/z88-348 · Cited by 602 · see citing works
Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus
Xu, R., Ekiert, D. C., Krause, J. C., Hai, R., Crowe, J. E., & Wilson, I. A. (2010) · Science · doi:10.1126/science.1186430 · Cited by 601 · see citing works
Cox, R. J., Brokstad, K. A., & Ogra, P. L. O. (2004) · Scandinavian Journal of Immunology · doi:10.1111/j.0300-9475.2004.01382.x · Cited by 553 · see citing works
Kunkel, E. J., & Butcher, E. C. (2003) · Nature reviews. Immunology · doi:10.1038/nri1203 · Cited by 537 · see citing works
Mortality benefits of influenza vaccination in elderly people: an ongoing controversy
Simonsen, L., Taylor, R. J., Viboud, C. G., Miller, M. A., & Jackson, L. A. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70236-0 · Cited by 520 · see citing works
Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen
Smith, K., Garman, L., Wrammert, J., Zheng, N., Capra, J. D., Ahmed, R., & Wilson, P. C. (2009) · Nature Protocols · doi:10.1038/nprot.2009.3 · Cited by 471 · see citing works
Self-citationNeutralizing antibodies derived from the B cells of 1918 influenza pandemic survivors
Yu, X., Tsibane, T., McGraw, P. A., House, F. S., Keefer, C. J., Hicar, M. D., Tumpey, T. M., Pappas, C., Perrone, L. A., Martinez, O., et al. (2008) · Nature · doi:10.1038/nature07231 · Cited by 448 · see citing works
Frasca, D., Landin, A. M., Lechner, S. C., Ryan, J. G., Schwartz, R., Riley, R. L., & Blomberg, B. B. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.8.5283 · Cited by 333 · see citing works
Romero‐Steiner, S., Musher, D. M., Cetron, M. S., Pais, L. B., Groover, J. E., & Carlone, G. M. (1999) · Clinical Infectious Diseases · doi:10.1086/520200 · Cited by 311 · see citing works
Tangye, S. G., Avery, D. T., Deenick, E. K., & Hodgkin, P. D. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.2.686 · Cited by 300 · see citing works
Age-related Defects in CD4 T Cell Cognate Helper Function Lead to Reductions in Humoral Responses
Eaton, S. M., Burns, E. M., Kusser, K. L., Randall, T. D., & Haynes, L. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20041395 · Cited by 279 · see citing works
Immunosenescence and germinal center reaction
Zheng, B. Q., Han, S., Takahashi, Y., & Kelsoe, G. H. (1997) · Immunological Reviews · doi:10.1111/j.1600-065x.1997.tb01028.x · Cited by 229 · see citing works
Influence of Prior Influenza Vaccination on Antibody and B-Cell Responses
Sasaki, S., He, X.-S., Holmes, T. H., Dekker, C. L., Kemble, G. W., Arvin, A. M., & Greenberg, H. B. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002975 · Cited by 229 · see citing works
Self-citationVaccination in the elderly: an immunological perspective
Chen, W. H., Kozlovsky, B. F., Effros, R. B., Grubeck‐Loebenstein, B., Edelman, R., & Sztein, M. B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.05.002 · Cited by 228 · see citing works
The Role of the Antibody Response in Influenza Virus Infection
Gerhard, W. (2001) · Current topics in microbiology and immunology · doi:10.1007/978-3-662-05783-4_9 · Cited by 211 · see citing works
Govaert, T. M. (1994) · JAMA · doi:10.1001/jama.272.21.1661 · Cited by 200 · see citing works
B cells and aging: molecules and mechanisms
Cancro, M. P., Hao, Y., Scholz, J. L., Riley, R. L., Frasca, D., Dunn-Walters, D. K., & Blomberg, B. B. (2009) · Trends in Immunology · doi:10.1016/j.it.2009.04.005 · Cited by 198 · see citing works
Sasaki, S., Jaimes, M. C., Holmes, T. H., Dekker, C. L., Mahmood, K., Kemble, G. W., Arvin, A. M., & Greenberg, H. B. (2006) · Journal of Virology · doi:10.1128/jvi.01957-06 · Cited by 196 · see citing works
Self-citationUsinger, W. R., & Lucas, A. H. (1999) · Infection and Immunity · doi:10.1128/iai.67.5.2366-2370.1999 · Cited by 172 · see citing works
Aging Affects Human B Cell Responses
Frasca, D., & Blomberg, B. B. (2011) · Journal of Clinical Immunology · doi:10.1007/s10875-010-9501-7 · Cited by 172 · see citing works
Cox, R. J., Brokstad, K. A., Zuckerman, M. A., Wood, J., Haaheim, L. R., & OXFORD, J. S. (1994) · Vaccine · doi:10.1016/0264-410x(94)90334-4 · Cited by 153 · see citing works
Intrinsic defects in B cell response to seasonal influenza vaccination in elderly humans
Frasca, D., Diaz, A., Romero, M., Landin, A. M., Phillips, M., Lechner, S. C., Ryan, J. G., & Blomberg, B. B. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.10.023 · Cited by 143 · see citing works
Skountzou, I., Koutsonanos, D. G., Kim, J. H., Powers, R. P., Satyabhama, L., Masseoud, F., Weldon, W. C., Martin, M. D. P., Mittler, R. S., Compans, R. W., et al. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000091 · Cited by 131 · see citing works
Good‐Jacobson, K. L., & Tangye, S. G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0703872104 · Cited by 126 · see citing works
Mechanisms for Decreased Function of B Cells in Aged Mice and Humans
Frasca, D., Landin, A. M., Riley, R. L., & Blomberg, B. B. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.2741 · Cited by 97 · see citing works
El‐Madhun, A. S., Cox, R. J., Søreide, A., Olofsson, J. S., & Haaheim, L. R. (1998) · The Journal of Infectious Diseases · doi:10.1086/515656 · Cited by 88 · see citing works
Immune Function and Vaccine Responses in Healthy Advanced Elderly Patients
Carson, P. J., Nichol, K. L., O'Brien, J., Hilo, P., & Janoff, E. N. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.13.2017 · Cited by 79 · see citing works
Kolibab, K., Smithson, S. L., Rabquer, B. J., Khuder, S., & Westerink, M. A. J. (2005) · Infection and Immunity · doi:10.1128/iai.73.11.7465-7476.2005 · Cited by 64 · see citing works
Plasmablast-derived polyclonal antibody response after influenza vaccination
He, X.-S., Sasaki, S., Narváez, C. F., Zhang, C., Liu, H., Woo, J. C., Kemble, G. W., Dekker, C. L., Davis, M. M., & Greenberg, H. B. (2010) · Journal of Immunological Methods · doi:10.1016/j.jim.2010.12.008 · Cited by 57 · see citing works
Self-citationAntibody diversity: one enzyme to rule them all
Nussenzweig, M. C., & Alt, F. W. (2004) · Nature Medicine · doi:10.1038/nm1204-1304 · Cited by 46 · see citing works
Sun, Y., Hwang, Y., & Nahm, M. H. (2001) · Infection and Immunity · doi:10.1128/iai.69.1.336-344.2001 · Cited by 45 · see citing works
Frasca, D., Nguyen, D. N., Riley, R. L., & Blomberg, B. B. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00009-5 · Cited by 32 · see citing works
Zheng, B. Q., Switzer, K. C., Marinova, E., Wansley, D. L., & Han, S. (2007) · Clinical Immunology · doi:10.1016/j.clim.2007.04.017 · Cited by 16 · see citing works
Bancos, S., & Phipps, R. P. (2010) · Cellular Immunology · doi:10.1016/j.cellimm.2010.09.002 · Cited by 13 · see citing works
Rectification of age-related impairment in Ig gene hypermutation during a memory response
Han, S. (2004) · International Immunology · doi:10.1093/intimm/dxh054 · Cited by 12 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Wardemann H, Yurasov S, Schaefer A, Young JW, Meffre E, Nussenzweig MC. Predominant autoan- tibody production by early human B cell precur- sors. Science. 2003;301(5638):1374-1377.
Cited by
Sorted by citations
Elements of cancer immunity and the cancer–immune set point
Chen, D. S., & Mellman, I. (2017) · Nature · doi:10.1038/nature21349 · Cited by 5,352 · see citing works
Emerging concepts in the science of vaccine adjuvants
Pulendran, B., Arunachalam, P. S., & O’Hagan, D. T. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00163-y · Cited by 1,417 · see citing works
Vaccine adjuvants: mechanisms and platforms
Zhao, T., Cai, Y., Jiang, Y., He, X., Wei, Y., Yu, Y., & Tian, X. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01557-7 · Cited by 961 · see citing works
Self-citationUnderstanding immunosenescence to improve responses to vaccines
Goronzy, J. J., & Weyand, C. M. (2013) · Nature Immunology · doi:10.1038/ni.2588 · Cited by 827 · see citing works
Causes, consequences, and reversal of immune system aging
Montecino-Rodriguez, E., Berent-Maoz, B., & Dorshkind, K. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64096 · Cited by 793 · see citing works
Immunosenescence and human vaccine immune responses
Crooke, S. N., Ovsyannikova, I. G., Poland, G. A., & Kennedy, R. B. (2019) · Immunity & Ageing · doi:10.1186/s12979-019-0164-9 · Cited by 530 · see citing works
Age-dependent Immune Response to the Biontech/Pfizer BNT162b2 Coronavirus Disease 2019 Vaccination
Müller, L., Andrée, M., Moskorz, W., Drexler, I., Walotka, L., Grothmann, R., Ptok, J., Hillebrandt, J., Ritchie, A., Rabl, D., et al. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciab381 · Cited by 511 · see citing works
The aging lung: Physiology, disease, and immunity
Schneider, J. L., Rowe, J. H., Garcia-de-Alba, C., Kim, C. F., Sharpe, A. H., & Haigis, M. C. (2021) · Cell · doi:10.1016/j.cell.2021.03.005 · Cited by 500 · see citing works
The immune system and aging: A review
Castelo-Branco, C., & Soveral, I. (2014) · Gynecological Endocrinology · doi:10.3109/09513590.2013.852531 · Cited by 449 · see citing works
Lineage Structure of the Human Antibody Repertoire in Response to Influenza Vaccination
Jiang, N., He, J., Weinstein, J. A., Penland, L., Sasaki, S., He, X.-S., Dekker, C. L., Zheng, N.-Y., Huang, M., Sullivan, M., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3004794 · Cited by 335 · see citing works
Self-citationNakaya, H. I., Hagan, T., Duraisingham, S. S., Lee, E. K., Kwissa, M., Rouphael, N., Frasca, D., Gersten, M., Mehta, A. K., Gaujoux, R., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.11.012 · Cited by 337 · see citing works
In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire
DeKosky, B. J., Kojima, T., Rodin, A., Charab, W., Ippolito, G. C., Ellington, A. D., & Georgiou, G. (2014) · Nature Medicine · doi:10.1038/nm.3743 · Cited by 358 · see citing works
Sex, the aging immune system, and chronic disease
Bupp, M. G. (2015) · Cellular Immunology · doi:10.1016/j.cellimm.2015.02.002 · Cited by 333 · see citing works
Metabolic Phenotypes of Response to Vaccination in Humans
Li, S., Sullivan, N., Rouphael, N., Yu, T., Banton, S., Maddur, M. S., McCausland, M. M., Chiu, C., Canniff, J. D., Dubey, S. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.04.026 · Cited by 277 · see citing works
Effectiveness of influenza vaccine in aging and older adults: comprehensive analysis of the evidence
Lang, P. O., Mendès, Socquet, Assir, Govind, & Aspinall, R. (2012) · Clinical Interventions in Aging · doi:10.2147/cia.s25215 · Cited by 242 · see citing works
McElhaney, J. E., Zhou, X., Talbot, H. K., Soethout, E., Bleackley, R. C., Granville, D. J., & Pawelec, G. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.01.015 · Cited by 229 · see citing works
Frasca, D., Diaz, A., Romero, M., Garcia, D., & Blomberg, B. B. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-011620-034148 · Cited by 226 · see citing works
Towards a universal influenza vaccine: different approaches for one goal
Sautto, G. A., Kirchenbaum, G. A., & Ross, T. M. (2018) · Virology Journal · doi:10.1186/s12985-017-0918-y · Cited by 202 · see citing works
Apoptosis and other immune biomarkers predict influenza vaccine responsiveness
Furman, D., Jojic, V., Kidd, B., Shen‐Orr, S., Price, J., Jarrell, J., Tse, T., Huang, H., Lund, P., Maecker, H. T., et al. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.15 · Cited by 184 · see citing works
Self-citationHerati, R. S., Reuter, M. A., Dolfi, D. V., Mansfield, K. D., Aung, H., Badwan, O. Z., Kurupati, R. K., Kannan, S., Ertl, H., Schmader, K. E., et al. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1302503 · Cited by 177 · see citing works
Effects of Aging, Cytomegalovirus Infection, and EBV Infection on Human B Cell Repertoires
Wang, C., Liu, Y., Xu, L. T., Jackson, K., Roskin, K. M., Pham, T. D., Laserson, J., Marshall, E. L., Seo, K., Lee, J.-Y., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1301384 · Cited by 179 · see citing works
Self-citationOrigin and Function of Circulating Plasmablasts during Acute Viral Infections
Fink, K. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00078 · Cited by 181 · see citing works
B cell maintenance and function in aging
Kogut, I., Scholz, J. L., Cancro, M. P., & Cambier, J. C. (2012) · Seminars in Immunology · doi:10.1016/j.smim.2012.04.004 · Cited by 166 · see citing works
Deeks, S. G., Verdin, E. M., & McCune, J. M. (2012) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.05.004 · Cited by 158 · see citing works
Understanding immunosenescence and its impact on vaccination of older adults
Allen, J. C., Toapanta, F. R., Chen, W. H., & Tennant, S. M. (2020) · Vaccine · doi:10.1016/j.vaccine.2020.11.002 · Cited by 157 · see citing works
Sex and Gender Impact Immune Responses to Vaccines Among the Elderly
Fink, A. L., & Klein, S. L. (2015) · Physiology · doi:10.1152/physiol.00035.2015 · Cited by 154 · see citing works
Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals
Henry, C., Zheng, N., Huang, M., Cabanov, A., Rojas, K. T., Kaur, K., Andrews, S. F., Palm, A.-K. E., Chen, Y.-Q., Li, Y., et al. (2019) · Cell Host & Microbe · doi:10.1016/j.chom.2019.01.002 · Cited by 142 · see citing works
Self-citationTools to therapeutically harness the human antibody response
Wilson, P. C., & Andrews, S. F. (2012) · Nature reviews. Immunology · doi:10.1038/nri3285 · Cited by 146 · see citing works
Self-citationFrasca, D., Diaz, A., Romero, M., & Blomberg, B. B. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.04.023 · Cited by 144 · see citing works
Recommendations for vaccination in multiple myeloma: a consensus of the European Myeloma Network
Ludwig, H., Boccadoro, M., Moreau, P., Miguel, J. F. S., Cavo, M., Pawlyn, C., Zweegman, S., Facon, T. T. F., Driessen, C., Hájek, R., et al. (2020) · Leukemia · doi:10.1038/s41375-020-01016-0 · Cited by 142 · see citing works
Sage, P. T., Tan, C. L., Freeman, G. J., Haigis, M. C., & Sharpe, A. H. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.06.015 · Cited by 141 · see citing works
Inactivated influenza vaccines
Fiore, A. E., Bridges, C. B., Katz, J. M., & Cox, N. J. (2013) · Elsevier eBooks · doi:10.1016/b978-1-4557-0090-5.00026-4 · Cited by 135 · see citing works
Aging and influenza vaccine-induced immunity
Dugan, H. L., Henry, C., & Wilson, P. C. (2019) · Cellular Immunology · doi:10.1016/j.cellimm.2019.103998 · Cited by 133 · see citing works
Self-citationThe Gracefully Aging Immune System
Boraschi, D., Aguado, M. T., Dutel, C., Goronzy, J. J., Louis, J. A., Grubeck‐Loebenstein, B., Rappuoli, R., & Giudice, G. D. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3005624 · Cited by 133 · see citing works
Aging induces B cell defects and decreased antibody responses to influenza infection and vaccination
Frasca, D., & Blomberg, B. B. (2020) · Immunity & Ageing · doi:10.1186/s12979-020-00210-z · Cited by 130 · see citing works
Systems vaccinology: Enabling rational vaccine design with systems biological approaches
Hagan, T., Nakaya, H. I., Subramaniam, S., & Pulendran, B. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.03.072 · Cited by 125 · see citing works
Dhakal, S., & Klein, S. L. (2019) · Journal of Virology · doi:10.1128/jvi.00797-19 · Cited by 123 · see citing works
The current challenges for vaccine development
Oyston, P. C. F., & Robinson, K. (2012) · Journal of Medical Microbiology · doi:10.1099/jmm.0.039180-0 · Cited by 119 · see citing works
The confounded effects of age and exposure history in response to influenza vaccination
Mosterín, A., McElhaney, J. E., Fonville, J. M., Powers, D. C., BEYER, W. E. P., & Smith, D. J. (2015) · Vaccine · doi:10.1016/j.vaccine.2015.11.058 · Cited by 112 · see citing works
Human B-1 Cells and B-1 Cell Antibodies Change With Advancing Age
Rodríguez‐Zhurbenko, N., Quách, T. D., Hopkins, T. J., Rothstein, T. L., & Hernández, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00483 · Cited by 111 · see citing works
A comparative review of aging and B cell function in mice and humans
Scholz, J. L., Diaz, A., Riley, R. L., Cancro, M. P., & Frasca, D. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.07.006 · Cited by 103 · see citing works
Immunosenescence and Novel Vaccination Strategies for the Elderly
Dorrington, M. G., & Bowdish, D. M. E. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00171 · Cited by 104 · see citing works
Cell culture-based influenza vaccines: A necessary and indispensable investment for the future
Hegde, N. R. (2015) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2015.1016666 · Cited by 103 · see citing works
Dunning, A. J., DiazGranados, C. A., Voloshen, T., Hu, B. T., Landolfi, V. A., & Talbot, H. K. (2016) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00604-15 · Cited by 101 · see citing works
Tan, Y., Blum, L. K., Kongpachith, S., Ju, C., Cai, X., Lindström, T. M., Sokolove, J. B., & Robinson, W. H. (2014) · Clinical Immunology · doi:10.1016/j.clim.2013.12.008 · Cited by 103 · see citing works
Age-Related Changes in Human Peripheral Blood IGH Repertoire Following Vaccination
Wu, Y.-C. B., Kipling, D., & Dunn‐Walters, D. K. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00193 · Cited by 101 · see citing works
Plasma cell numbers decrease in bone marrow of old patients
Pritz, T., Lair, J., Ban, M., Keller, M., Weinberger, B., Krismer, M., & Grubeck‐Loebenstein, B. (2015) · European Journal of Immunology · doi:10.1002/eji.201444878 · Cited by 98 · see citing works
Factors affecting immune responses to the influenza vaccine
Castrucci, M. R. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1338547 · Cited by 97 · see citing works
Autophagy and Immune Senescence
Zhang, H., Puleston, D. J., & Simon, A. K. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.06.001 · Cited by 93 · see citing works
Amantadine and rimantadine for influenza A in children and the elderly
Galvão, M. G. A., Santos, M. A. R. C., & da Cunha, A. J. A. (2008) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002745.pub2 · Cited by 91 · see citing works
Stiasny, K., Aberle, J. H., Keller, M., Grubeck‐Loebenstein, B., & Heinz, F. X. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034145 · Cited by 88 · see citing works
Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine
Frasca, D., Diaz, A., Romero, M., Phillips, M., Mendez, N. V., Landin, A. M., & Blomberg, B. B. (2012) · International Immunology · doi:10.1093/intimm/dxr123 · Cited by 86 · see citing works
Atsmon, J., Caraco, Y., Ziv-Sefer, S., Shaikevich, D., Abramov, E., Volokhov, I., Bruzil, S., Haima, K. Y., Gottlieb, T. M., & Ben-Yedidia, T. (2014) · Vaccine · doi:10.1016/j.vaccine.2014.08.031 · Cited by 88 · see citing works
Khurana, S., Frasca, D., Blomberg, B., & Golding, H. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1002920 · Cited by 85 · see citing works
Hong, H., Wang, Q., Li, J., Liu, H. B., Meng, X., & Zhang, H. (2019) · Journal of Cancer · doi:10.7150/jca.30723 · Cited by 89 · see citing works
Immunosenescence and vaccine failure in the elderly: strategies for improving response
Boraschi, D., & Italiani, P. (2014) · Immunology Letters · doi:10.1016/j.imlet.2014.06.006 · Cited by 86 · see citing works
Najarro, K., Nguyen, H., Chen, G., Xu, M., Alcorta, S., Yao, X., Zukley, L., Metter, E. J., Truong, T., Lin, Y., et al. (2015) · Journal of Infectious Diseases · doi:10.1093/infdis/jiv202 · Cited by 83 · see citing works
A systems biology approach to the effect of aging, immunosenescence and vaccine response
Poland, G. A., Ovsyannikova, I. G., Kennedy, R. B., Lambert, N. D., & Kirkland, J. L. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.04.005 · Cited by 85 · see citing works
Nuñez, I. A., Carlock, M. A., Allen, J. D., Owino, S. O., Geffel, K. M., Nowalk, M. P., Susick, M., Diagle, K., Sweeney, K., Mundle, S. T., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0185666 · Cited by 85 · see citing works
Aging and Interferons: Impacts on Inflammation and Viral Disease Outcomes
Feng, E., Balint, E., Poznanski, S. M., Ashkar, A. A., & Loeb, M. B. (2021) · Cells · doi:10.3390/cells10030708 · Cited by 87 · see citing works
To, K. K., Zhang, J., Hung, I. F., Xu, T., Ip, W. C., Wong, R. T. Y., Ng, J. C. K., Chan, J. F., Chan, K., & Yuen, K. (2012) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00081-12 · Cited by 83 · see citing works
Immunobiology of Influenza Vaccines
Lorenzo, M. M. G., & Fenton, M. J. (2013) · CHEST Journal · doi:10.1378/chest.12-1711 · Cited by 83 · see citing works
Host Resistance and Immune Aging
Bandaranayake, T., & Shaw, A. C. (2016) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2016.02.007 · Cited by 85 · see citing works
Ortmann, W., & Kolaczkowska, E. (2018) · Cell and Tissue Research · doi:10.1007/s00441-017-2751-4 · Cited by 80 · see citing works
Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection
Merani, S., Pawelec, G., Kuchel, G. A., & McElhaney, J. E. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00784 · Cited by 74 · see citing works
Martineau, A. R., Hanifa, Y., Witt, K. D., Barnes, N. C., Hooper, R., Patel, M., Stevens, N. J., Enayat, Z. E., Balayah, Z., Syed, A., et al. (2015) · Thorax · doi:10.1136/thoraxjnl-2015-206996 · Cited by 80 · see citing works
Human adaptive immune receptor repertoire analysis—Past, present, and future
Nielsen, S. C. A., & Boyd, S. D. (2018) · Immunological Reviews · doi:10.1111/imr.12667 · Cited by 80 · see citing works
Immune responses to influenza virus and its correlation to age and inherited factors
Bahadoran, A., Lee, S. H., Wang, S. M., Manikam, R., Rajarajeswaran, J., Raju, C. S., & Sekaran, S. D. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01841 · Cited by 79 · see citing works
Rejuvenating conventional dendritic cells and T follicular helper cell formation after vaccination
Stebegg, M., Bignon, A., Hill, D. L., Silva-Cayetano, A., Krueger, C., Vanderleyden, I., Innocentin, S., Boon, L., Wang, J., Zand, M. S., et al. (2020) · eLife · doi:10.7554/elife.52473 · Cited by 74 · see citing works
The ocular surface immune system through the eyes of aging
Galletti, J. G., & de Paiva, C. S. (2021) · The Ocular Surface · doi:10.1016/j.jtos.2021.02.007 · Cited by 76 · see citing works
Haralambieva, I. H., Painter, S. D., Kennedy, R. B., Ovsyannikova, I. G., Lambert, N. D., Goergen, K. M., Oberg, A. L., & Poland, G. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122282 · Cited by 75 · see citing works
Avivi, I. M., Balaban, R., Shragai, T., Sheffer, G., Morales, M., Aharon, A., Lowenton‐Spier, N., Trestman, S., Perry, C., Benyamini, N., et al. (2021) · British Journal of Haematology · doi:10.1111/bjh.17608 · Cited by 74 · see citing works
Mechanisms underpinning poor antibody responses to vaccines in ageing
Lee, J. L., & Linterman, M. A. (2021) · Immunology Letters · doi:10.1016/j.imlet.2021.11.001 · Cited by 71 · see citing works
Preexisting subtype immunodominance shapes memory B cell recall response to influenza vaccination
Abreu, R. B., Kirchenbaum, G. A., Clutter, E. F., Sautto, G. A., & Ross, T. M. (2019) · JCI Insight · doi:10.1172/jci.insight.132155 · Cited by 71 · see citing works
Triggering Intracellular Receptors for Vaccine Adjuvantation
Gutjahr, A., Tiraby, G., Pérouzel, É., Verrier, B., & Paul, S. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.07.001 · Cited by 73 · see citing works
How T follicular helper cells and the germinal centre response change with age
Linterman, M. A. (2014) · Immunology & Cell Biology · doi:10.1038/icb.2013.77 · Cited by 69 · see citing works
Imprinting, immunodominance, and other impediments to generating broad influenza immunity
Knight, M., Changrob, S., Li, L., & Wilson, P. C. (2020) · Immunological Reviews · doi:10.1111/imr.12900 · Cited by 69 · see citing works
Self-citationKhurana, S., Verma, N., Talaat, K. R., Karron, R. A., & Golding, H. (2011) · The Journal of Infectious Diseases · doi:10.1093/infdis/jir791 · Cited by 67 · see citing works
B Cell Responses to Influenza Infection and Vaccination
Chiu, C., Ellebedy, A. H., Wrammert, J., & Ahmed, R. (2014) · Current topics in microbiology and immunology · doi:10.1007/82_2014_425 · Cited by 64 · see citing works
Self-citationImmunosenescence, Aging, and Systemic Lupus Erythematous
Montoya-Ortiz, G. (2013) · Autoimmune Diseases · doi:10.1155/2013/267078 · Cited by 65 · see citing works
Pilkinton, M. A., Nicholas, K. J., Warren, C. M., Smith, R. M., Yoder, S. M., Talbot, H. K., & Kalams, S. A. (2016) · Vaccine · doi:10.1016/j.vaccine.2016.11.059 · Cited by 64 · see citing works
Human lymphocyte repertoires in ageing
Boyd, S. D., Liu, Y., Wang, C., Martin, V., & Dunn‐Walters, D. K. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2013.07.007 · Cited by 61 · see citing works
Sangster, M. Y., Baer, J., Santiago, F. W., Fitzgerald, T. F., Ilyushina, N. A., Sundararajan, A., Henn, A. D., Krammer, F., Yang, H., Luke, C. J., et al. (2013) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00735-12 · Cited by 59 · see citing works
Verma, N., Dimitrova, M., Carter, D. M., Crevar, C. J., Ross, T. M., Golding, H., & Khurana, S. (2012) · Journal of Virology · doi:10.1128/jvi.07085-11 · Cited by 60 · see citing works
B cell function and influenza vaccine responses in healthy aging and disease
Frasca, D., & Blomberg, B. B. (2014) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.05.008 · Cited by 59 · see citing works
The recent advances in vaccine adjuvants
Xing, J., Zhao, X., Li, X., Fang, R., Sun, M., Zhang, Y., & Song, N. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1557415 · Cited by 62 · see citing works
Ward, B. J., Pillet, S., Charland, N., Trépanier, S., Couillard, J., & Landry, N. (2017) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2017.1413518 · Cited by 58 · see citing works
Amantadine and rimantadine for influenza A in children and the elderly
Galvão, M. G. A., Santos, M. A. R. C., & da Cunha, A. J. A. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd002745.pub4 · Cited by 59 · see citing works
Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine
Kay, A. W., Bayless, N. L., Fukuyama, J., Aziz, N., Dekker, C. L., Mackey, S., Swan, G. E., Davis, M. M., & Blish, C. A. (2015) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiv138 · Cited by 57 · see citing works
Self-citationWhelan, J. T., Gowdy, K. M., & Shaikh, S. R. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.03.100 · Cited by 56 · see citing works
Nicolay, U., Heijnen, E., Nacci, P., PATRIARCA, P. A., & Leav, B. A. (2019) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2019.03.026 · Cited by 55 · see citing works
Immune Senescence and Vaccination in the Elderly
Lang, P. O., Govind, S., ten Bokum, A., Kenny, N., Matas, E., Pitts, D. G., & Aspinall, R. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/15680266113136660181 · Cited by 54 · see citing works
Paradoxical aging in HIV: immune senescence of B Cells is most prominent in young age
Rinaldi, S., Pallikkuth, S., George, V. K., de Armas, L. R., Pahwa, R., Sanchez, C. M., Pallin, M., Pan, L., Cotugno, N., Dickinson, G. M., et al. (2017) · Aging · doi:10.18632/aging.101229 · Cited by 55 · see citing works
Aging and Options to Halt Declining Immunity to Virus Infections
Palacios-Pedrero, M. Á., Osterhaus, A. D. M. E., Becker, T., Elbahesh, H., Rimmelzwaan, G. F., & Saletti, G. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.681449 · Cited by 55 · see citing works
Tete, S. M., Bijl, M., Sahota, S., & Bos, N. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00257 · Cited by 56 · see citing works
Sanei, F., & Wilkinson, T. M. A. (2016) · Therapeutic Advances in Respiratory Disease · doi:10.1177/1753465816646050 · Cited by 54 · see citing works
Immunotherapy in older patients with cancer
Granier, C., Gey, A., Roncelin, S., Weiss, L., Paillaud, É., & Tartour, É. (2020) · Biomedical Journal · doi:10.1016/j.bj.2020.07.009 · Cited by 56 · see citing works
Huang, K.-Y. A., Li, C. K., Clutterbuck, E., Chui, C., Wilkinson, T. M. A., Gilbert, A., OXFORD, J. S., Lambkin‐Williams, R., Lin, T., McMichael, A. J., et al. (2014) · The Journal of Infectious Diseases · doi:10.1093/infdis/jit650 · Cited by 52 · see citing works
Microbiota–host interactions shape ageing dynamics
Popkes, M., & Valenzano, D. R. (2020) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2019.0596 · Cited by 51 · see citing works
B Cell Responses against Influenza Viruses: Short-Lived Humoral Immunity against a Life-Long Threat
Guthmiller, J. J., Utset, H. A., & Wilson, P. C. (2021) · Viruses · doi:10.3390/v13060965 · Cited by 52 · see citing works
Self-citation
- Authors
- Sasaki, S., Sullivan, M., Narvaez, C. F., Holmes, T. H., Furman, D., Zheng, N.-Y., Nishtala, M., Wrammert, J., Smith, K., James, J. A., Dekker, C. L., Davis, M. M., Wilson, P. C., Greenberg, H. B., & He, X.-S.
- Affiliations
- Stanford Medicine (US)
- University of Chicago (US)
- Emory University (US)
- Oklahoma Medical Research Foundation (US)
- Stanford University (US)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2011-08-01
- Volume
- 121
- Issue
- 8
- Pages
- 3109-3119
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3148747
- OpenAlex
- W2105359173
- Cited by
- 300
- References
- 52
- Citations by year
- 2026: 14 · 2025: 13 · 2024: 8 · 2023: 21 · 2022: 18 · 2021: 33 · 2020: 15 · 2019: 26 · 2018: 15 · 2017: 22 · 2016: 18 · 2015: 20 · 2014: 19 · 2013: 27 · 2012: 25
- FWCI
- 18.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI090023, AI057266, AI057229, DK56339)
- National Institute of Allergy and Infectious Diseases (AI 057229, AI057158, U19AI090023, U19AI090019, AI057266, HHSN266200500026C, AI090023, U54AI057158, U19AI057229, U19AI057266)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-56339, P30DK056339)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR053483)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- inactivated influenza vaccine, vaccine efficacy, older adults, plasmablasts, antibody avidity, antibody affinity, 2009 H1N1 pandemic, cross-reactivity, exposure history, B cells, monoclonal antibodies
- MeSH terms
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Antibodies, Antibodies, Monoclonal, Antibody Affinity, Enzyme-Linked Immunosorbent Assay, Humans, Immunoglobulin A, Immunoglobulin G, Influenza, Human, Influenza Vaccines, Plasma Cells, Young Adult
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