Lack of Peripheral Memory B Cell Responses in Recovered Patients with Severe Acute Respiratory Syndrome: A Six-Year Follow-Up Study
Abstract
Six years have passed since the outbreak of severe acute respiratory syndrome (SARS). Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time in recovered SARS patients. It is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another SARS outbreak. Recovered SARS patients were followed up to 6 y to estimate the longevity of specific Ab. The specific memory B cell and T cell responses to SARS-CoV Ags were measured by means of ELISPOT assay. Factors in relation to humoral and cellular immunity were investigated. Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients. Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls. Patients with more severe clinical manifestations seemed to present a higher level of Ag-specific memory T cell response. SARS-specific IgG Ab may eventually vanish and peripheral memory B cell responses are undetectable in recovered SARS patients. In contrast, specific T cell anamnestic responses can be maintained for at least 6 y. These findings have applications in preparation for the possible reemergence of SARS.
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Following natural infection of humans with SARS-CoV, neutralizing antibody and memory B cell responses in some individuals are short lived (~3 years), whereas memory T cells persist for at least 6 years.
“Following natural infection of humans with the related SARS-CoV, neutralizing antibody and memory B cell responses in some individuals are reported to be short lived (~ 3 years), whereas memory T cells persist for at least 6 years (54–56)”
From An <i>Alphavirus</i> -derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates (2020) · cites this paper as [54]
Cites
Immunological memory and protective immunity: understanding their relation
Ahmed, R., & Gray, D. (1996) · Science · doi:10.1126/science.272.5258.54 · Cited by 1,775 · cited 2× · see citing works
“attained in concert with the H1-specific plasma cells and memory B cells rather than memory T cells alone (14).”
BackgroundThe Severe Acute Respiratory Syndrome
Peiris, J. S. M., Yuen, K., Osterhaus, A. D. M. E., & Stöhr, K. (2003) · New England Journal of Medicine · doi:10.1056/nejmra032498 · Cited by 1,377 · see citing works
Duration of Humoral Immunity to Common Viral and Vaccine Antigens
Amanna, I. J., Carlson, N. E., & Slifka, M. K. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa066092 · Cited by 1,286 · see citing works
Humoral Immunity Due to Long-Lived Plasma Cells
Slifka, M. K., Antia, R., Whitmire, J. K., & Ahmed, R. (1998) · Immunity · doi:10.1016/s1074-7613(00)80541-5 · Cited by 1,249 · see citing works
Lung pathology of fatal severe acute respiratory syndrome
Nicholls, J. M., Poon, L. L., Lee, K. C., Ng, W. F., Lai, S. T., Leung, C. Y., Chu, C. M., Hui, P. K., Mak, K. L., Lim, W., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)13413-7 · Cited by 1,076 · see citing works
Duration of antiviral immunity after smallpox vaccination
Hammarlund, E., Lewis, M. W., Hansen, S. G., Strelow, L. I., Nelson, J. A., Sexton, G. J., Hanifin, J. M., & Slifka, M. K. (2003) · Nature Medicine · doi:10.1038/nm917 · Cited by 946 · see citing works
Lifetime of plasma cells in the bone marrow
Manz, R. A., Thiel, A., & Radbruch, A. (1997) · Nature · doi:10.1038/40540 · Cited by 866 · see citing works
Cutting edge: long-term B cell memory in humans after smallpox vaccination
Crotty, S., Felgner, P., Davies, H., Glidewell, J., Villarreal, L., & Ahmed, R. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.171.10.4969 · Cited by 695 · see citing works
A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice
Yang, Z.-Y., Kong, W., Huang, Y., Roberts, A., Murphy, B., Subbarao, K., & Nabel, G. (2004) · Nature · doi:10.1038/nature02463 · Cited by 688 · see citing works
Antibodies, viruses and vaccines
Burton, D. R. (2002) · Nature Reviews Immunology · doi:10.1038/nri891 · Cited by 637 · see citing works
T Cell Responses to Whole SARS Coronavirus in Humans
Li, C. K., Wu, H., Yan, H., Ma, S., Wang, L., Zhang, M., Tang, X., Temperton, N. J., Weiss, R. A., Brenchley, J. M., et al. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.8.5490 · Cited by 499 · see citing works
Diagnosis and Management of Smallpox
Breman, J. G., & Henderson, D. A. (2002) · New England Journal of Medicine · doi:10.1056/nejmra020025 · Cited by 463 · see citing works
Duration of Antibody Responses after Severe Acute Respiratory Syndrome
Wu, L.-P., Wang, N.-C., Chang, Y.-H., Tian, X.-Y., Na, D.-Y., Zhang, L.-Y., Zheng, L., Lan, T., Wang, L.-F., & Liang, G.-D. (2007) · Emerging Infectious Diseases · doi:10.3201/eid1310.070576 · Cited by 426 · see citing works
Tracking human antigen-specific memory B cells: a sensitive and generalized ELISPOT system
Crotty, S., Aubert, R. D., Glidewell, J., & Ahmed, R. (2004) · Journal of Immunological Methods · doi:10.1016/j.jim.2003.12.015 · Cited by 421 · see citing works
Disappearance of Antibodies to SARS-Associated Coronavirus after Recovery
Cao, W.-C., Liu, W., Zhang, P.-H., Zhang, F., & Richardus, J. H. (2007) · New England Journal of Medicine · doi:10.1056/nejmc070348 · Cited by 367 · see citing works
Self-citationAntibodies and B Cell Memory in Viral Immunity
Dörner, T., & Radbruch, A. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.002 · Cited by 290 · see citing works
Wong, K. T., Antonio, G. E., Hui, D. S. C., Lee, N. L. S., Yuen, E. H. Y., Wu, A. K. L., Leung, C. B., Rainer, T. H., Cameron, P. A., Chung, S. S. C., et al. (2003) · Radiology · doi:10.1148/radiol.2282030593 · Cited by 289 · see citing works
Liu, W. Y., Fontanet, A. L., Zhang, P., Zhan, L., Xin, Z., Baril, L., Tang, F., Lv, H., & Cao, W. (2006) · The Journal of Infectious Diseases · doi:10.1086/500469 · Cited by 282 · see citing works
Self-citationImmunological memory in humans
Crotty, S., & Ahmed, R. (2004) · Seminars in Immunology · doi:10.1016/j.smim.2004.02.008 · Cited by 228 · see citing works
Severe Acute Respiratory Syndrome
Christian, M. D., Poutanen, S. M., Loutfy, M. R., Muller, M. P., & Low, D. E. (2004) · Clinical Infectious Diseases · doi:10.1086/420743 · Cited by 224 · see citing works
Zhang, L., Zhang, F., Yu, W., Tian, H., Yu, J., Yi, C. E., Ba, L., Li, W., Farzan, M., Chen, Z., et al. (2005) · Journal of Medical Virology · doi:10.1002/jmv.20499 · Cited by 184 · see citing works
Differentiation of memory B and T cells
Kalia, V., Sarkar, S., Gourley, T. S., Rouse, B. T., & Ahmed, R. (2006) · Current Opinion in Immunology · doi:10.1016/j.coi.2006.03.020 · Cited by 184 · see citing works
Compromised B Cell Responses to Influenza Vaccination in HIV‐Infected Individuals
Malaspina, A., Moir, S. L., Orsega, S., et al. (2005) · The Journal of Infectious Diseases · doi:10.1086/429298 · Cited by 172 · see citing works
Longitudinally Profiling Neutralizing Antibody Response to SARS Coronavirus with Pseudotypes
Temperton, N. J., Chan, P. K. S., Simmons, G., Zambon, M. C. F. A., Tedder, R. S., Takeuchi, Y., & Weiss, R. A. (2005) · Emerging infectious diseases · doi:10.3201/eid1103.040906 · Cited by 155 · see citing works
Fan, Y., Huang, Z., Li, L., Wu, M., Yu, T., Koup, R. A., Bailer, R. T., & Wu, C. Y. (2009) · Archives of Virology · doi:10.1007/s00705-009-0409-6 · Cited by 150 · see citing works
He, Y., Zhou, Y., Wu, H., Luo, B., Chen, J., Li, W., & Jiang, S. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.6.4050 · Cited by 142 · see citing works
Germinal Centers and Antibody Production in Bone Marrow
Tew, J. G., Dilosa, R. M., Burton, G. F., et al. (1992) · Immunological Reviews · doi:10.1111/j.1600-065x.1992.tb00633.x · Cited by 134 · see citing works
Anti-SARS-CoV IgG response in relation to disease severity of severe acute respiratory syndrome
Lee, N. L. S., Chan, P. K. S., Ip, M., Wong, E., Ho, J., Ho, C., Cockram, C. S., & Hui, D. S. C. (2005) · Journal of Clinical Virology · doi:10.1016/j.jcv.2005.07.005 · Cited by 119 · see citing works
Yang, L., Peng, H., Zhu, Z.-L., Li, G., Huang, Z., Zhao, Z., Koup, R. A., Bailer, R. T., & Wu, C. Y. (2006) · Clinical Immunology · doi:10.1016/j.clim.2006.05.002 · Cited by 115 · see citing works
Zhi, Y., Kobinger, G., Jordan, H. M., Suchma, K., Weiss, S. R., Shen, H., Schumer, G., Gao, G., Boyer, J. L., Crystal, R. G., et al. (2005) · Virology · doi:10.1016/j.virol.2005.01.050 · Cited by 82 · see citing works
Chen, W., Xu, Z., Mu, J., et al. (2004) · Journal of Medical Microbiology · doi:10.1099/jmm.0.45561-0 · Cited by 72 · see citing works
Ochsenbein, A. F., Karrer, U. W., Klenerman, P., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.16.9293 · Cited by 66 · see citing works
Severe acute respiratory syndrome
Wang, J., & Chang, S. (2004) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-200404000-00013 · Cited by 61 · see citing works
Fondere, J.-M., Huguet, M., Macura-Biegun, A., et al. (2004) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200402010-00002 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Adaptive immunity to SARS-CoV-2 and COVID-19
Sette, A., & Crotty, S. (2021) · Cell · doi:10.1016/j.cell.2021.01.007 · Cited by 1,860 · see citing works
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19
Sekine, T., Perez-Potti, A., Rivera-Ballesteros, O., Strålin, K., Gorin, J.-B., Olsson, A., Llewellyn-Lacey, S., Kamal, H., Bogdanovic, G., Muschiol, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.017 · Cited by 1,788 · see citing works
Immunology of COVID-19: Current State of the Science
Vabret, N., Britton, G. J., Gruber, C., Hegde, S., Kim, J., Kuksin, M., Levantovsky, R., Malle, L., Moreira, A., Park, M. D., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.05.002 · Cited by 1,623 · see citing works
A dynamic COVID-19 immune signature includes associations with poor prognosis
Laing, A. G., Lorenc, A., del Molino del Barrio, I., Das, A., Fish, M., Monin, L., Muñoz-Ruiz, M., McKenzie, D. R., Hayday, T. S., Francos-Quijorna, I., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1038-6 · Cited by 946 · see citing works
BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans
Sahin, U., Muik, A., Vogler, I., Derhovanessian, E., Kranz, L. M., Vormehr, M., Quandt, J., Bidmon, N., Ulges, A., Baum, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03653-6 · Cited by 845 · see citing works
Immune response, inflammation, and the clinical spectrum of COVID-19
García, L. F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01441 · Cited by 739 · see citing works
Huang, A. T., Garcia-Carreras, B., Hitchings, M. D. T., Yang, B., Katzelnick, L. C., Rattigan, S. M., Borgert, B. A., Moreno, C. A., Solomon, B. D., Trimmer-Smith, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18450-4 · Cited by 1,026 · see citing works
Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19
Rodda, L. B., Netland, J., Shehata, L., Pruner, K. B., Morawski, P. A., Thouvenel, C. D., Takehara, K. K., Eggenberger, J., Hemann, E. A., Waterman, H. R., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.029 · Cited by 647 · see citing works
SARS-CoV-2-derived peptides define heterologous and COVID-19-induced T cell recognition
Nelde, A., Bilich, T., Heitmann, J. S., Maringer, Y., Salih, H. R., Roerden, M., Lübke, M., Bauer, J., Rieth, J., Wacker, M., et al. (2021) · Nature Immunology · doi:10.1038/s41590-020-00808-x · Cited by 582 · see citing works
Immunological characteristics govern the transition of COVID-19 to endemicity
Lavine, J. S., Bjornstad, O. N., & Antia, R. (2021) · Science · doi:10.1126/science.abe6522 · Cited by 416 · see citing works
COVID-19 Coronavirus Vaccine Design Using Reverse Vaccinology and Machine Learning
Ong, E., Wong, M. U., Huffman, A., & He, Y. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01581 · Cited by 499 · see citing works
Airway Memory CD4+ T Cells Mediate Protective Immunity against Emerging Respiratory Coronaviruses
Zhao, J., Zhao, J., Mangalam, A. K., Channappanavar, R., Fett, C., Meyerholz, D. K., Agnihothram, S., Baric, R. S., David, C. S., & Perlman, S. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.006 · Cited by 496 · see citing works
Ortiz-Prado, E., Simbaña-Rivera, K., Gómez- Barreno, L., Rubio-Neira, M., Guaman, L. P., Kyriakidis, N. C., Muslin, C., Jaramillo, A. M. G., Barba-Ostria, C., Cevallos-Robalino, D., et al. (2020) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2020.115094 · Cited by 458 · see citing works
Channappanavar, R., Fett, C., Zhao, J., Meyerholz, D. K., & Perlman, S. (2014) · Journal of Virology · doi:10.1128/jvi.01505-14 · Cited by 411 · see citing works
Ferretti, A. P., Kula, T., Wang, Y., Nguyen, D. M. V., Weinheimer, A., Dunlap, G. S., Xu, Q., Nabilsi, N., Perullo, C. R., Cristofaro, A. W., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.10.006 · Cited by 318 · see citing works
Lessons for COVID-19 immunity from other coronavirus infections
Sariol, A., & Perlman, S. (2020) · Immunity · doi:10.1016/j.immuni.2020.07.005 · Cited by 317 · see citing works
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Cromer, D., Juno, J. A., Khoury, D., Reynaldi, A., Wheatley, A. K., Kent, S. J., & Davenport, M. P. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-021-00550-x · Cited by 265 · see citing works
Hartley, G. E., Edwards, E. S. J., Aui, P. M., Varese, N., Stojanovic, S., McMahon, J., Peleg, A. Y., Boo, I., Drummer, H. E., Hogarth, P. M., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.abf8891 · Cited by 296 · see citing works
Erasmus, J. H., Khandhar, A. P., O’Connor, M. A., Walls, A. C., Hemann, E. A., Murapa, P., Archer, J., Leventhal, S., Fuller, J. T., Lewis, T. B., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abc9396 · Cited by 241 · see citing works
Wang, K., Long, Q.-X., Deng, H.-J., Hu, J., Gao, Q.-Z., Zhang, G.-J., He, C.-L., Huang, L.-Y., Hu, J.-L., Chen, J., et al. (2021) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa1143 · Cited by 218 · see citing works
Neidleman, J., Luo, X., Frouard, J., Xie, G., Gill, G., Stein, E. S., McGregor, M., Ma, T., George, A. F., Kosters, A., et al. (2020) · Cell Reports Medicine · doi:10.1016/j.xcrm.2020.100081 · Cited by 188 · see citing works
The known unknowns of T cell immunity to COVID-19
Karlsson, A. C., Humbert, M., & Buggert, M. (2020) · Science Immunology · doi:10.1126/sciimmunol.abe8063 · Cited by 165 · see citing works
Direct Observation of Repeated Infections With Endemic Coronaviruses
Galanti, M., & Shaman, J. (2021) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaa392 · Cited by 149 · see citing works
Persistent cellular immunity to SARS-CoV-2 infection
Breton, G., Mendoza, P., Hägglöf, T., Oliveira, T. Y., Schaefer-Babajew, D., Gaebler, C., Turroja, M., Hurley, A., Caskey, M., & Nussenzweig, M. C. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202515 · Cited by 129 · see citing works
Abayasingam, A., Balachandran, H., Agapiou, D., Hammoud, M., Rodrigo, C., Keoshkerian, E., Li, H., Brasher, N. A., Christ, D., Rouet, R., et al. (2021) · Cell Reports Medicine · doi:10.1016/j.xcrm.2021.100228 · Cited by 78 · see citing works
Ahmed-Hassan, H., Sisson, B., Shukla, R. K., Wijewantha, Y., Funderburg, N. T., Li, Z., Hayes, D., Demberg, T., & Liyanage, N. P. M. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01979 · Cited by 47 · see citing works
- Authors
- Tang, F., Quan, Y., Xin, Z.-T., Wrammert, J., Ma, M.-J., Lv, H., Wang, T.-B., Yang, H., Richardus, J. H., Liu, W., & Cao, W.-C.
- Affiliations
- Chinese People's Armed Police Force (CN)
- Chengdu Military General Hospital (CN)
- Chinese National Human Genome Center (CN)
- Emory University (US)
- Beijing Institute of Microbiology and Epidemiology (CN)
- Chinese People’s Armed Forces Hospital of Beijing , Beijing 100027 ,
- Erasmus MC (NL)
- Corresponding author
- Tang, Fang
- Yang, Hong
- Liu, Wei
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06
- Volume
- 186
- Issue
- 12
- Pages
- 7264-7268
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1662940398
- Cited by
- 496
- References
- 34
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 24 · 2023: 34 · 2022: 74 · 2021: 155 · 2020: 171 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 11 · 2015: 1 · 2014: 2 · 2012: 1
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Outbreaks Research
- Keywords
- SARS, SARS-CoV, memory B cells, memory T cells, secondary immune response, antibody waning, long-term immunity, reinfection, close contacts, humoral immunity, cell-mediated immunity, disease severity
- MeSH terms
- Adult, Antigens, Viral, B-Lymphocytes, Disease Outbreaks, Female, Follow-Up Studies, Humans, Immunity, Cellular, Immunologic Memory, Male, Middle Aged, T-Lymphocytes, Case-Control Studies, Severe Acute Respiratory Syndrome, Severe acute respiratory syndrome-related coronavirus, Immunity, Humoral, Enzyme-Linked Immunospot Assay
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