Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

Lederer, Katlyn; Parvathaneni, Kalpana; Painter, Mark M.; Bettini, Emily; Agarwal, Divyansh; Lundgreen, Kendall A.; Weirick, Madison; Goel, Rishi R.; Xu, Xiaoming; Drapeau, Elizabeth M.; Gouma, Sigrid; Greenplate, Allison R.; Coz, Carole Le; Romberg, Neil; Jones, Lisa; Rosen, Mark; Besharatian, Behdad; Kaminiski, Mary; Weiskopf, Daniela; Sette, Alessandro; Hensley, Scott E.; Bates, Paul; Wherry, E. John; Naji, Ali; Bhoj, Vijay; Locci, Michela

doi:10.1101/2021.09.16.21263686

PreprintCited by 179SARS-CoV-2 and COVID-19 ResearchT-cell and B-cell ImmunologyImmune responses and vaccinations

Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

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Lederer, Katlyn, Parvathaneni, Kalpana, Painter, Mark M., Bettini, Emily, Agarwal, Divyansh, Lundgreen, Kendall A., Weirick, Madison, Goel, Rishi R. +18 more·2021·Cell

DOI 10.1101/2021.09.16.21263686PMC PMC8475965

Preprint — published as 10.1016/j.cell.2022.01.027

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Abstract

SUMMARY: Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. In this study, through a fine-needle-aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant (KTX) recipients. We found that, unlike healthy subjects, KTX recipients presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cells, SARS-CoV-2 receptor-binding-domain-specific memory B cells and neutralizing antibodies. KTX recipients also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals, and suggest a GC-origin for certain humoral and memory B cell responses following mRNA vaccination.

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mRNA vaccines induce robust germinal center responses in humans, resulting in memory B cells specific for full-length spike and RBD.
“mRNA vaccines induce robust germinal center responses in humans (14, 15), which result in memory B cells that are specific for both the full-length SARS-CoV-2 spike protein and the spike receptor-binding domain (RBD) (16–18).”
From mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern (2021) · cites this paper as [15]

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Greaney, A. J., Loes, A. N., Gentles, L. E., Crawford, K. H. D., Starr, T. N., Malone, K. D., Chu, H. Y., & Bloom, J. D. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abi9915 · Cited by 244 · see citing works
Impaired humoral and cellular immunity after SARS-CoV-2 BNT162b2 (tozinameran) prime-boost vaccination in kidney transplant recipients
Sattler, A., Schrezenmeier, E. V., Weber, U., Potekhin, A., Bachmann, F., Straub-Hohenbleicher, H., Budde, K., Storz, E., Proß, V., Bergmann, Y., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci150175 · Cited by 242 · see citing works
Cellular and humoral response after MRNA-1273 SARS-CoV-2 vaccine in kidney transplant recipients
Cucchiari, D., Egri, N., Bodro, M., et al. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16701 · Cited by 231 · see citing works
Modified mRNA Vaccines Protect against Zika Virus Infection
Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., Julander, J. G., Tang, W. W., Shresta, S., Pierson, T. C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.03.016 · Cited by 221 · see citing works
Modified mRNA/lipid nanoparticle-based vaccines expressing respiratory syncytial virus F protein variants are immunogenic and protective in rodent models of RSV infection
Espeseth, A. S., Cejas, P. J., Citron, M. P., Wang, D., DiStefano, D. J., Callahan, C., Donnell, G. O., Galli, J. D., Swoyer, R., Touch, S., et al. (2020) · npj Vaccines · doi:10.1038/s41541-020-0163-z · Cited by 190 · see citing works
Circulating CXCR5+PD-1+ Response Predicts Influenza Vaccine Antibody Responses in Young Adults but not Elderly Adults
Herati, 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
Self-citation
Expression of Functional Recombinant Hemagglutinin and Neuraminidase Proteins from the Novel H7N9 Influenza Virus Using the Baculovirus Expression System
Margine, I., Palese, P., & Krammer, F. (2013) · Journal of Visualized Experiments · doi:10.3791/51112 · Cited by 169 · see citing works
T follicular helper cells in human efferent lymph retain lymphoid characteristics
Vella, L. A., Buggert, M., Manne, S., Herati, R. S., Sayin, I., Kuri-Cervantes, L., Bukh Brody, I., O’Boyle, K. C., Kaprielian, H., Giles, J. R., et al. (2019) · Journal of Clinical Investigation · doi:10.1172/jci125628 · Cited by 155 · see citing works
Self-citation
A novel receptor-binding domain (RBD)-based mRNA vaccine against SARS-CoV-2
Tai, W., Zhang, X., Drelich, A., Shi, J., Hsu, J. C., Luchsinger, L., Hillyer, C. D., Tseng, C.-T. K., Jiang, S., & Du, L. (2020) · Cell Research · doi:10.1038/s41422-020-0387-5 · Cited by 151 · see citing works
Induction of robust B cell responses after influenza mRNA vaccination Is accompanied by circulating hemagglutinin-specific ICOS+ PD-1+ CXCR3+ T follicular helper cells
Lindgren, G., Ols, S., Liang, F., Thompson, E. A., Lin, A., Hellgren, F., Bahl, K., John, S., Yuzhakov, O., Hassett, K. J., et al. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01539 · Cited by 132 · see citing works
SARS-CoV-2 seroprevalence among parturient women in Philadelphia
Flannery, D. D., Gouma, S., Dhudasia, M. B., Mukhopadhyay, S., Pfeifer, M. R., Woodford, E. C., Gerber, J. S., Arevalo, C. P., Bolton, M. J., Weirick, M. E., et al. (2020) · Science Immunology · doi:10.1126/sciimmunol.abd5709 · Cited by 125 · see citing works
Self-citation
Human Circulating T Follicular Helper Cell Subsets in Health and Disease
Ueno, H. (2016) · Journal of Clinical Immunology · doi:10.1007/s10875-016-0268-3 · Cited by 122 · see citing works
Vaccination establishes clonal relatives of germinal center T cells in the blood of humans
Heit, A., Schmitz, F., Gerdts, S. E., Flach, B., Moore, M. S., Perkins, J. A., Robins, H. S., Aderem, A. A., Spearman, P. W., Tomaras, G. D., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161794 · Cited by 115 · see citing works
Nucleoside-modified mRNA encoding HSV-2 glycoproteins C, D, and E prevents clinical and subclinical genital herpes
Awasthi, S., Hook, L. M., Pardi, N., Wang, F., Myles, A., Cancro, M. P., Cohen, G. H., Weissman, D., & Friedman, H. M. (2019) · Science Immunology · doi:10.1126/sciimmunol.aaw7083 · Cited by 115 · see citing works
Immune response to an adjuvanted influenza A H1N1 vaccine (Pandemrix(R)) in renal transplant recipients
Brakemeier, S., Schweiger, B., Lachmann, N., Glander, P., Schönemann, C., Diekmann, F., Neumayer, H. H., & Budde, K. (2011) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfr278 · Cited by 73 · see citing works
Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis
Broeders, N., Hombrouck, A., Lemy, A., et al. (2011) · Clinical Journal of the American Society of Nephrology · doi:10.2215/cjn.04670511 · Cited by 73 · see citing works
Data Driven Statistical Methods
Sprent, P. (2019) · Routledge eBooks · doi:10.1201/9781315140780 · Cited by 65 · see citing works
Normal human lymph node T follicular helper cells and germinal center B cells accessed via fine needle aspirations
Havenar‐Daughton, C., Newton, I. G., Zare, S., Reiss, S. M., Schwan, B., Suh, M. J., Hasteh, F., Levi, G., & Crotty, S. (2020) · Journal of Immunological Methods · doi:10.1016/j.jim.2020.112746 · Cited by 50 · see citing works
A randomized, controlled clinical trial to evaluate the immunogenicity of a PreS/S hepatitis B vaccine Sci-B-Vac™, as compared to Engerix B®, among vaccine naïve and vaccine non-responder dialysis patients
Elhanan, E., Boaz, M., Schwartz, I. F., et al. (2017) · Clinical and Experimental Nephrology · doi:10.1007/s10157-017-1416-7 · Cited by 43 · see citing works
Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy
(2021) · doi:10.1101/2021.06.23.21259389 · Cited by 39 · see citing works
Impact of Immunosuppression on Recall Immune Responses to Influenza Vaccination in Stable Renal Transplant Recipients
Cowan, M. L., Chon, W. J., Desai, A., Andrews, S. F., Bai, Y., Veguilla, V., Katz, J. M., Josephson, M. A., Wilson, P. C., Sciammas, R., et al. (2013) · Transplantation · doi:10.1097/01.tp.0000438024.10375.2d · Cited by 34 · see citing works
Comparing Humoral and Cellular Immune Response Against HBV Vaccine in Kidney Transplant Patients
Friedrich, P., Sattler, A., Müller, K., Nienen, M., Reinke, P., & Babel, N. (2015) · American Journal of Transplantation · doi:10.1111/ajt.13380 · Cited by 24 · see citing works
Rapid induction of antigen-specific CD4 + T cells guides coordinated humoral and cellular immune responses to SARS-CoV-2 mRNA vaccinationPreprint
Painter, M. M., Mathew, D., Goel, R. R., Apostolidis, S. A., Pattekar, A., Kuthuru, O., Baxter, A. E., Herati, R. S., Oldridge, D. A., Gouma, S., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.21.440862 · Cited by 23 · see citing works
Self-citation
Safety and Cross-Variant Immunogenicity of a Three-Dose COVID-19 mRNA Vaccine Regimen in Kidney Transplant RecipientsPreprint
Massa, F., Crémoni, M., Gérard, A. O., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3890865 · Cited by 16 · see citing works
High-affinity, neutralizing antibodies to SARS-CoV-2 can be made in the absence of T follicular helper cellsPreprint
Chen, J., Chow, R. D.-W., Song, E., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.06.10.447982 · Cited by 11 · see citing works

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Sorted by citations

mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern
Goel, R. R., Painter, M. M., Apostolidis, S. A., Mathew, D., Meng, W., Rosenfeld, A. M., Lundgreen, K. A., Reynaldi, A., Khoury, D. S., Pattekar, A., et al. (2021) · Science · doi:10.1126/science.abm0829 · Cited by 873 · see citing works
Self-citation
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses
Alameh, M., Tombácz, I., Bettini, E., Lederer, K., Sittplangkoon, C., Wilmore, J. R., Gaudette, B. T., Soliman, O. Y., Pine, M., Hicks, P. D., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.05.007 · Cited by 77 · see citing works
“Because SARS-CoV-2 nucleoside-modified mRNA-LNP vaccines promote robust GC B cell and Tfh cell responses in humans (Lederer et al., 2021; Mudd et al., 2021; Turner et al., 2021), we argue that a similar pro-Tfh cellinducing activity is also present in humans and that the mechanism could also likely…”
Self-citation
Humoral and cellular immune memory to four COVID-19 vaccines
Zhang, Z., Mateus, J., Coelho, C. H., Dan, J. M., Moderbacher, C. R., Gálvez, R. I., Côrtes, F. H., Grifoni, A., Tarke, A., Chang, J., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.022 · Cited by 567 · see citing works
“SARSCoV-2 spike-specific circulating follicular helper T (cTfh) cells were measured at all time points (Figures 3C and S2D), as this subpopulation of CD4 T cells is crucial for supporting antibody responses following vaccination (Crotty, 2019; Lederer et al., 2022; Mudd et al., 2022).”
Self-citation
Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination
Röltgen, K., Nielsen, S. C. A., Silva, O., Younes, S. F., Zaslavsky, M., Costales, C., Yang, F., Wirz, O. F., Solis, D., Hoh, R. A., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.018 · Cited by 459 · see citing works
Immunological memory to SARS‐CoV ‐2 infection and COVID ‐19 vaccines
Sette, A., & Crotty, S. (2022) · Immunological Reviews · doi:10.1111/imr.13089 · Cited by 266 · see citing works
Self-citation
BNT162b2 vaccination induces durable SARS-CoV-2–specific T cells with a stem cell memory phenotype
Guerrera, G., Picozza, M., D’Orso, S., Placido, R., Pirronello, M., Verdiani, A., Termine, A., Fabrizio, C., Giannessi, F., Sambucci, M., et al. (2021) · Science Immunology · doi:10.1126/sciimmunol.abl5344 · Cited by 222 · see citing works
“Induction of Tfh cells also occurs in response to the Spike protein (58, 59), and our finding of Spike-specific cells expressing CXCR5, PD-1, and ICOS suggests that mRNA vaccination is effective in generating CD4+ cells able to interact with B cells, in line with other studies (13, 15, 17, 60).”
Result
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses
Alameh, M.-G., Tombácz, I., Bettini, E., Lederer, K., Ndeupen, S., Sittplangkoon, C., Wilmore, J. R., Gaudette, B. T., Soliman, O. Y., Pine, M., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.11.001 · Cited by 775 · see citing works
“Because SARS-CoV-2 nucleoside-modified mRNA-LNP vaccines promote robust GC B cell and Tfh cell responses in humans (Lederer et al., 2021; Mudd et al., 2021; Turner et al., 2021), we argue that a similar pro-Tfh cellinducing activity is also present in humans and that the mechanism could also likely…”
Self-citation
Memory B cells
Inoue, T., & Kurosaki, T. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00897-3 · Cited by 227 · see citing works
“Indeed, nAb responses are substantially reduced in many individuals who are immunocompromised, such as recipients of kidney trans-plants 138 .”
Antibody-mediated neutralization of SARS-CoV-2
Gruell, H., Vanshylla, K., Weber, T., Barnes, C. O., Kreer, C., & Klein, F. (2022) · Immunity · doi:10.1016/j.immuni.2022.05.005 · Cited by 145 · see citing works
“SARS-CoV-2-reactive germinal center B and T follicular helper cells became detectable within 2–3 weeks of immunization and were associated with the development of neutralizing antibodies (Lederer et al., 2022; Mudd et al., 2022; Schmitz et al., 2021; Turner et al., 2021b).”
The immunostimulatory nature of mRNA lipid nanoparticles
Sharma, P., Hoorn, D., Aitha, A., Breier, D., & Peer, D. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115175 · Cited by 132 · see citing works
Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections
Terreri, S., Piano Mortari, E., Vinci, M. R., Russo, C., Alteri, C., Albano, C., Colavita, F., Gramigna, G., Agrati, C., Linardos, G., et al. (2022) · Cell Host & Microbe · doi:10.1016/j.chom.2022.01.003 · Cited by 117 · see citing works
“Through the recirculation in the persistent germinal centers demonstrated in vaccinated individuals (Lederer et al., 2021; Turner et al., 2021b), MBCs may continuously be re-stimulated, thus explaining their increased numbers and progressively improved antigen affinity (Piano Mortari et al.”
SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
Alsoussi, W. B., Malladi, S. K., Zhou, J. Q., Liu, Z., Ying, B., Kim, W., Schmitz, A. J., Lei, T., Horvath, S. C., Sturtz, A. J., et al. (2023) · Nature · doi:10.1038/s41586-023-06025-4 · Cited by 167 · see citing works
Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals
Connors, J. R., Joyner, D., Mege, N. J., Cusimano, G. M., Bell, M. R., Marcy, J., Taramangalam, B., Kim, K. M., Lin, P. J. C., Tam, Y. K., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-04555-1 · Cited by 124 · see citing works
“These vaccines utilize four-component lipid nanoparticles (LNPs) that have been shown to potently induce IL-1, IL-6 secretion, T FH and GC B cell generation in humans 1,10,36 – 38 .”
SARS-CoV-2-specific T cells in the changing landscape of the COVID-19 pandemic
Bertoletti, A., Bert, N. L., & Tan, A. T. (2022) · Immunity · doi:10.1016/j.immuni.2022.08.008 · Cited by 115 · see citing works
“…at odds with the apparent exclusive localization of tissue-resident S-specific T cells in the lymph node draining the site of mRNA injections (Lederer et al., 2022; Mudd et al., 2022; Turner et al., 2021) and also with recent works that detected tissue-resident S-specific T cells only in the…”
Prior vaccination promotes early activation of memory T cells and enhances immune responses during SARS-CoV-2 breakthrough infection
Painter, M. M., Johnston, T. S., Lundgreen, K. A., Santos, J. J. S., Qin, J. S., Goel, R. R., Apostolidis, S. A., Mathew, D., Fulmer, B., Williams, J. C., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01613-y · Cited by 106 · see citing works
Self-citation
Human circulating and tissue-resident memory CD8+ T cells
Buggert, M., Price, D. A., Mackay, L. K., & Betts, M. R. (2023) · Nature Immunology · doi:10.1038/s41590-023-01538-6 · Cited by 119 · see citing works
“Although most human vaccine studies to date have focused on the generation of immune responses in the vasculature, a few investigators have gone beyond the exclusive use of peripheral blood samples to assess memory B and CD4 + T cell responses in biopsied LNs 159,160,161,162 .”
Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine
Hu, X., Karthigeyan, K. P., Herbek, S. L., Valencia, S. M., Jenks, J. A., Webster, H. S., Miller, I. G., Connors, M., Pollara, J., Andy, C., et al. (2024) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiad593 · Cited by 82 · see citing works
Linking vaccine adjuvant mechanisms of action to function
Ben‐Akiva, E., Chapman, A. P., Mao, T., & Irvine, D. J. (2025) · Science Immunology · doi:10.1126/sciimmunol.ado5937 · Cited by 76 · see citing works
Duration of SARS-CoV-2 mRNA vaccine persistence and factors associated with cardiac involvement in recently vaccinated patients
Krauson, A. J., Casimero, F. V. C., Siddiquee, Z., et al. (2023) · npj Vaccines · doi:10.1038/s41541-023-00742-7 · Cited by 72 · see citing works
“We did not detect vaccine mRNA in mediastinal lymph nodes, consistent with the previous observation that SARS-CoV-2 mRNA vaccines elicit antigen-speci ﬁ c germinal center B cell responses only in draining lymph nodes 24 .”
Result
Infection or a third dose of mRNA vaccine elicits neutralizing antibody responses against SARS-CoV-2 in kidney transplant recipients
Charmetant, X., Espi, M., Benotmane, I., Barateau, V., Heibel, F., Buron, F., Gautier-Vargas, G., Delafosse, M., Perrin, P., Koenig, A., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abl6141 · Cited by 77 · see citing works
“…capacity and antigen-specific germinal center B cells after vaccination do not only correlate with the number of antigen-specific Tfh1 cells, the subset predominantly produced after vaccination in healthy participants ( 53 , 54 ), but also with the two other Tfh subsets (Tfh2 and Tfh17).”
Instructing durable humoral immunity for COVID-19 and other vaccinable diseases
Bhattacharya, D. (2022) · Immunity · doi:10.1016/j.immuni.2022.05.004 · Cited by 63 · see citing works
“As discussed above, germinal centers continue to producememory B cells of enhanced breadth over the course of months after SARS-CoV-2 infections or vaccines (Lederer et al., 2022; Muecksch et al., 2022b; Turner et al., 2021; Wang et al., 2021).”
Influential
Extended SARS-CoV-2 RBD booster vaccination induces humoral and cellular immune tolerance in mice
Gao, F., Wu, R., Shen, M., Huang, J., Li, T., Hu, C., Luo, F., Song, S., Mu, S., Hao, Y., et al. (2022) · iScience · doi:10.1016/j.isci.2022.105479 · Cited by 54 · see citing works
SARS-CoV-2 Omicron boosting induces de novo B cell response in humans
Alsoussi, W. B., Malladi, S. K., Zhou, J. Q., et al. (2022) · bioRxiv · doi:10.1101/2022.09.22.509040 · Cited by 47
The MegaPool Approach to Characterize Adaptive CD4+ and CD8+ T Cell Responses
Antunes, R. D. S., Weiskopf, D., Sidney, J., Rubiro, P., Peters, B., Arlehamn, C. S. L., Grifoni, A., & Sette, A. (2023) · Current Protocols · doi:10.1002/cpz1.934 · Cited by 46 · see citing works
“…2020; Hassan et al., 2020; He et al., 2022; Hsieh et al., 2022; Jin et al., 2021; Keeton et al., 2021; Kee-ton et al., 2022; Keeton et al., 2023; Lederer et al., 2022; Madelon, Heikkila, et al., 2022; Madelon, Lauper, et al., 2022; Mateus et al., 2021; Mateus, Grifoni, Tarke, et al., 2020;…”
Self-citation
Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses
Tomalka, J. A., Suthar, M. S., Deeks, S. G., & Sékaly, R. (2022) · Nature Immunology · doi:10.1038/s41590-022-01130-4 · Cited by 45 · see citing works
Distinct components of mRNA vaccines cooperate to instruct efficient germinal center responses
Castaño, D., Bettini, E., Kumar, B., Chudnovskiy, A., Siv, A., Protti, G., Nakandakari-Higa, S., Ceglia, S., Luna, N. D., Chiu, J. E., et al. (2025) · Cell · doi:10.1016/j.cell.2025.11.023 · Cited by 43 · see citing works
Self-citation
Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues
Davis‐Porada, J., George, A. B., Lam, N., Caron, D. P., Gray, J. I., Huang, J., Hwu, J., Wells, S. B., Matsumoto, R., Kubota, M., et al. (2024) · Immunity · doi:10.1016/j.immuni.2024.10.003 · Cited by 36 · see citing works
Self-citation
A third dose of the unmodified COVID-19 mRNA vaccine CVnCoV enhances quality and quantity of immune responses
Lenart, K., Hellgren, F., Ols, S., Yan, X., Cagigi, A., Cerveira, R. A., Winge, I. P., Hanczak, J., Mueller, S. O., Jasny, E., et al. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.10.001 · Cited by 39 · see citing works
mRNA vaccines in tumor targeted therapy: mechanism, clinical application, and development trends
Gao, Y., Yang, L., Li, Z., Peng, X., & Li, H. (2024) · Biomarker Research · doi:10.1186/s40364-024-00644-3 · Cited by 33 · see citing works
“4) High interindividual variability: Differences in genetic background, immune status, and disease conditions among individuals influence the immunogenicity and therapeutic efficacy of mRNA vaccines [224].”
Background
Adenovirus vector and mRNA vaccines: Mechanisms regulating their immunogenicity
Provine, N. M., & Klenerman, P. (2022) · European Journal of Immunology · doi:10.1002/eji.202250022 · Cited by 37 · see citing works
Immune imprinting: The persisting influence of the first antigenic encounter with rapidly evolving viruses
Maltseva, M., Keeshan, A., Cooper, C., & Langlois, M. (2024) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2024.2384192 · Cited by 33 · see citing works
A Pvs25 mRNA vaccine induces complete and durable transmission-blocking immunity to Plasmodium vivax
Kunkeaw, N., Nguitragool, W., Takashima, E., Kangwanrangsan, N., Muramatsu, H., Tachibana, M., Ishino, T., Lin, P. J. C., Tam, Y. K., Pichyangkul, S., et al. (2023) · npj Vaccines · doi:10.1038/s41541-023-00786-9 · Cited by 34 · see citing works
“The great ability of nucleoside-modi ﬁ ed mRNA – LNP vaccination to elicit GC B and Tfh cells has been revealed in animal models 27,29 as well as in humans immunized with SARS-CoV-2 mRNA vaccines 46,47 .”
Background
T follicular helper cells in the humoral immune response to SARS-CoV-2 infection and vaccination
Koutsakos, M., Lee, W. S., Wheatley, A. K., Kent, S. J., & Juno, J. A. (2021) · Journal of Leukocyte Biology · doi:10.1002/jlb.5mr0821-464r · Cited by 36 · see citing works
Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates
Buckley, M., Araínga, M., Maiorino, L., et al. (2024) · bioRxiv · doi:10.1101/2024.06.21.600088 · Cited by 25 · see citing works
“…to be a feature of the NHP model that may be distinct from humans, as longitudinal fine needle aspirate studies of volunteers receiving the COVID-19 mRNA vaccines have been quite successful in detecting robust ongoing germinal center responses simply by sampling draining axillary LNs 34,35 .”
Disease-associated B cells and immune endotypes shape adaptive immune responses to SARS-CoV-2 mRNA vaccination in human SLE
Faliti, C. E., Van, T. T. P., Anam, F. A., Cheedarla, N., Williams, M. E., Mishra, A. K., Usman, S. Y., Woodruff, M. C., Kraker, G., Runnstrom, M. C., et al. (2024) · Nature Immunology · doi:10.1038/s41590-024-02010-9 · Cited by 23 · see citing works
“Clinical efficacy and immune correlates of mRNA vaccination have been amply tested in the healthy population and in patients with cancer 33,45 or solid organ transplantation 46–48 .”
Hybrid Immunity against SARS-CoV-2 Variants: A Narrative Review of the Literature
Tsagkli, P., Geropeppa, M., Papadatou, I., & Spoulou, V. I. (2024) · Vaccines · doi:10.3390/vaccines12091051 · Cited by 22 · see citing works
Differences in SARS-CoV-2 specific humoral and cellular immune responses after contralateral and ipsilateral COVID-19 vaccination
Ziegler, L., Klemis, V., Schmidt, T., Schneitler, S., Baum, C., Neumann, J., Becker, S. L., Gärtner, B. C., Sester, U., & Sester, M. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104743 · Cited by 25 · see citing works
T-Cell Immune Responses to SARS-CoV-2 Infection and Vaccination
Notarbartolo, S. (2024) · Vaccines · doi:10.3390/vaccines12101126 · Cited by 21 · see citing works
“…after the second immunization, S-specific T FH cells in lymph nodes persist at least for 6 months [143], and their impairment is strictly associated with compromised germinal center reactions and nAbs production, as shown in immunocompromised individuals undergoing kidney transplantation [144].”
Background
Longitudinal cellular and humoral immune responses after triple BNT162b2 and fourth full-dose mRNA-1273 vaccination in haemodialysis patients
Becker, M., Cossmann, A., Lürken, K., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1004045 · Cited by 17
Immunogenicity, breakthrough infection, and underlying disease flare after SARS-CoV-2 vaccination among individuals with systemic autoimmune rheumatic diseases
Paik, J. J., Sparks, J. A., & Kim, A. H. J. (2022) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2022.102243 · Cited by 18 · see citing works
Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccinationPreprint
Kim, W., Zhou, J. Q., Sturtz, A. J., Horvath, S. C., Schmitz, A. J., Lei, T., Kalaidina, E., Thapa, M., Alsoussi, W. B., Haile, A., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.31.466651 · Cited by 18 · see citing works
Establishing long-lasting vaccine immunity: insights from mRNA and adjuvanted protein platforms
Pineda-Peña, A.-C., Hasegawa, K., Pavot, V., Berry, C., Combadière, B., Cortés-Garcia, G., McDermott, A. B., & Sridhar, S. (2025) · npj Vaccines · doi:10.1038/s41541-025-01302-x · Cited by 23 · see citing works
“In parallel, germinal center T FH cells persisted in draining lymph nodes following mRNA vaccinations 136 , supporting the maintenance of germ-inal center reaction and contributing to durable antibody production 128,137 .”
Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19
Priest, D. G., Ebihara, T., Tulyeu, J., Søndergaard, J. N., Sakakibara, S., Sugihara, F., Nakao, S., Togami, Y., Yoshimura, J., Ito, H., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50997-4 · Cited by 23 · see citing works
SARS-CoV-2 Omicron escapes mRNA vaccine booster-induced antibody neutralisation in patients with autoimmune rheumatic diseases: an observational cohort study
Kim, W.-J., Choi, S., Park, J. Y., Song, J. S., Chung, J.-W., & Choi, S. T. (2022) · Annals of the Rheumatic Diseases · doi:10.1136/ard-2022-222689 · Cited by 20 · see citing works
Advancement in the development of mRNA ‐based vaccines for respiratory viruses
Troncoso‐Bravo, T., Ramírez, M. A., Loaiza, R. A., Román-Cárdenas, C., Papazisis, G., Garrido, D. A., González, P. A., Bueno, S. M., & Kalergis, A. M. (2024) · Immunology · doi:10.1111/imm.13844 · Cited by 17 · see citing works
“In mRNA-vaccinated mice, germinal centre B cell and follicular T helper cell responses are significantly amplified and correlate with the magnitude and durability of antibody responses [61].”
SARS-CoV-2 spike-specific TFH cells exhibit unique responses in infected and vaccinated individuals
He, R., Zheng, X., Zhang, J., Liu, B., Wang, Q., Wu, Q., Liu, Z., Chang, F., Hu, Y., Xie, T., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01650-x · Cited by 19 · see citing works
Tissue immunity to SARS‐CoV‐2: Role in protection and immunopathology*
Rybkina, K., Davis‐Porada, J., & Färber, D. L. (2022) · Immunological Reviews · doi:10.1111/imr.13112 · Cited by 19 · see citing works
T and B cell responses in different immunization scenarios for COVID-19: a narrative review
Mortari, E. P., Ferrucci, F., Zografaki, I., Carsetti, R., & Pacelli, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1535014 · Cited by 13 · see citing works
Early antiviral CD4+ and CD8+ T cells are associated with upper airway clearance of SARS-CoV-2
Ramirez, S. I., Lopez, P. G., Faraji, F., Parikh, U. M., Heaps, A., Ritz, J., Moser, C., Eron, J. J., Wohl, D. A., Currier, J. S., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.186078 · Cited by 21 · see citing works
“Given the biological dependence of the antibody response on CD4 + T cell help mediated by Tfh (50, 51), some statistical association between antibodies and viral load would always be expected, even if, hypothet-ically, viral control were exclusively mediated by T cells.”
Self-citation
Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations
Purcell, R. A., Theisen, R. M., Arnold, K. B., Chung, A. W., & Selva, K. J. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1183727 · Cited by 15 · see citing works
Non-Omicron breakthrough infection with higher viral load and longer vaccination-infection interval improves SARS-CoV-2 BA.4/5 neutralization
Miyamoto, S., Arashiro, T., Ueno, A., Kanno, T., Saito, S., Katano, H., Iida, S., Ainai, A., Ozono, S., Hemmi, T., et al. (2023) · iScience · doi:10.1016/j.isci.2023.105969 · Cited by 13 · see citing works
Cellular and Humoral Immunity against Different SARS-CoV-2 Variants Is Detectable but Reduced in Vaccinated Kidney Transplant Patients
Thümmler, L., Gäckler, A., Bormann, M., et al. (2022) · Vaccines · doi:10.3390/vaccines10081348 · Cited by 13
The cellular factors that impair the germinal center in advanced age
Foster, W. S., Marcial‐Juárez, E., & Linterman, M. A. (2025) · The Journal of Immunology · doi:10.1093/jimmun/vkae039 · Cited by 14 · see citing works
The survival of B cells is compromised in kidney disease
Peroumal, D., Jawale, C. V., Choi, W., Rahimi, H., Antos, D., Li, D., Wang, S., Vijay, G. K. M., Mehta, I. D., West, R. E., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-55187-w · Cited by 14 · see citing works
“A recent study showed compromised GC-derived immunity in kidney transplant patients following SARS-CoV-2 mRNA vaccination 25 .”
Infection-mediated immune response in SARS-CoV-2 breakthrough infection and implications for next-generation COVID-19 vaccine development
Miyamoto, S., & Suzuki, T. (2024) · Vaccine · doi:10.1016/j.vaccine.2024.01.088 · Cited by 13 · see citing works
Prior SARS-CoV-2 Infection Enhances Initial mRNA Vaccine Response with a Lower Impact on Long-Term Immunity
Silva‐Moraes, V., Souquette, A. H., Sautto, G. A., Paciello, I., Antonelli, G., Andreano, E., Rappuoli, R., Teixeira‐Carvalho, A., & Ross, T. M. (2023) · ImmunoHorizons · doi:10.4049/immunohorizons.2300041 · Cited by 10 · see citing works
Activation‐induced marker assays for identification of Trypanosoma cruzi ‐specific CD4 or CD8 T cells in chronic Chagas disease patients
Ferragut, F., Cruz, K. M., Gallardo, J. P., Fernandez, M. L., Vasquez, Y. H., & Gómez, K. A. (2022) · Immunology · doi:10.1111/imm.13622 · Cited by 12 · see citing works
Lessons from SENCOVAC: A prospective study evaluating the response to SARS-CoV-2 vaccination in the CKD spectrum
Quiroga, B., Soler, M. J., Ortíz, A., & de Sequera, P. (2023) · Nefrología (English Edition) · doi:10.1016/j.nefroe.2023.04.005 · Cited by 9 · see citing works
T cell help in the autoreactive germinal center
Akama‐Garren, E. H., & Carroll, M. C. (2022) · Scandinavian Journal of Immunology · doi:10.1111/sji.13192 · Cited by 16 · see citing works
Long-lasting germinal center responses to a priming immunization with continuous proliferation and somatic mutation
Lee, J. H., Sutton, H., Cottrell, C., et al. (2021) · bioRxiv · doi:10.1101/2021.12.20.473537 · Cited by 10
Highly functional and prolonged germinal center T follicular helper cell responses are associated with enhanced neutralizing antibody development
Marina-Zárate, E., Sutton, H. J., Lopez, P. G., Altheide, T. K., Bick, M., Burton, I., Ben‐Akiva, E., Michaels, K. K., Hyacinth, K., Healy, B. S., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.10.008 · Cited by 15 · see citing works
Fine needle aspiration of human lymph nodes reveals cell populations and soluble interactors pivotal to immunological priming
Provine, N. M., Al‐Diwani, A., Agarwal, D., Dooley, K., Heslington, A., Murchison, A. G., Garner, L. C., Sheerin, F., Klenerman, P., & Irani, S. R. (2024) · European Journal of Immunology · doi:10.1002/eji.202350872 · Cited by 12 · see citing works
“This approach has permitted studying both B cells and T-follicular helper (T FH ) cells, which support GC formation and maintenance [15].”
Self-citation
Insights From Early Clinical Trials Assessing Response to mRNA SARS-CoV-2 Vaccination in Immunocompromised Patients
Baron, F., Canti, L., Ariën, K. K., Kemlin, D., Desombere, I., Gerbaux, M., Pannus, P., Beguin, Y. P., Marchant, A., & Humblet‐Baron, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.827242 · Cited by 12 · see citing works
“A recent study (still in pre-print format) reported an extensive comparison of immunogenicity of anti-SARS-CoV-2 mRNA vaccine in healthy subjects and in 10 kidney transplant recipients (129).”
Background
Immune Response to MVA-BN Vaccination for Mpox: Current Evidence and Future Directions
Byrne, J., Katoto, P., Kirenga, B., et al. (2025) · Vaccines · doi:10.3390/vaccines13090930 · Cited by 8
“Although mRNA vaccines, such as those targeting SARS-CoV-2, have been shown to induce prolonged germinal centre activity [71], this may not be a universal feature of all non-replicating platforms.”
Evaluating PFAS-Induced modulation of peripheral blood mononuclear cells (PBMCs) immune response to SARS-CoV-2 spike in COVID-19 Vaccinees
Ayuk, H. S., Pierzchalski, A., Tal, T. L., Myhre, O., Lindeman, B., Smith, N. M., Stojanovska, V., & Zenclussen, A. C. (2025) · Environment International · doi:10.1016/j.envint.2025.109409 · Cited by 5 · see citing works
T follicular helper cell responses to SARS‐CoV ‐2 vaccination among healthy and immunocompromised adults
Boyd, M. A. A., Hoppé, A. C., Kelleher, A. D., & Munier, C. M. L. (2023) · Immunology and Cell Biology · doi:10.1111/imcb.12635 · Cited by 7 · see citing works
“compared LN FNB samples from healthy participants (n = 15) and those on immunosuppressant drugs following kidney transplant (n = 13).(67) Draining and nondraining (n = 4) LNs were sampled 14 days following primary and 8 days following secondary SARS-CoV-2 mRNA vaccination.”
BackgroundInfluential
Impact of Metabolic States on SARS-CoV-2 Vaccine Responses in Mouse Models of Obesity and Diabetes
Smith, O. A., Fujimoto, B., Wong, T. A. S., To, A., Odo, T., Ball, A. H., Haun, B. K., Muramatsu, H., Tam, Y. K., Pardi, N., et al. (2024) · COVID · doi:10.3390/covid5010002 · Cited by 6 · see citing works
“Adjuvanted vaccines likely promote robust affinity maturation due to prolonged antigen exposure’s “depot effect” [77,78], while modified mRNA vaccines promote strong affinity maturation through Tfh cell and GC activation [71– 74].”
A cluster of broadly neutralizing IgG against BK polyomavirus in a repertoire dominated by IgM
Nguyen, N., Devilder, M., Gautreau-Rolland, L., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202201567 · Cited by 6
Validation of ligand tetramers for the detection of antigen-specific lymphocytes
Fitzpatrick, K., Degefu, H. N., Poljakov, K., et al. (2022) · bioRxiv · doi:10.1101/2022.10.24.513230 · Cited by 6
“For antigen-specific B cell detection, the most used tools are fluorochrome-conjugated antigen/peptide tetramers, fluorochrome-conjugated virus-like particles as well as other types of fluorochromeconjugated ligands (For an incomplete crosssection, see (1-232)).”
Method
Immunogenicity of SARS-CoV-2 Trimeric Spike Protein Associated to Poly(I:C) Plus Alum
dos-Santos, J. S., Firmino-Cruz, L., da Fonseca-Martins, A. M., Oliveira-Maciel, D., Pérez, G., Pereira, V. A. R., Dumard, C. H., Guedes-da-Silva, F. H., Santos, A. C. V., Leandro, M. D. S., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.884760 · Cited by 7 · see citing works
The comprehensive insights into the B-cells-mediated immune response against COVID-19 infection amid the ongoing evolution of SARS-CoV-2
Dhawan, M. K., Thakur, N., Sharma, M. K., & Rabaan, A. A. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.117936 · Cited by 5 · see citing works
Cowpox to COVID: History of vaccination in the immunocompromised host
Schaenman, J. M. D., & Avery, R. K. (2023) · Transplant Infectious Disease · doi:10.1111/tid.14051 · Cited by 6 · see citing works
Saturation time of exposure interval for cross-neutralization response to SARS-CoV-2: Implications for vaccine dose interval
Miyamoto, S., Kuroda, Y., Kanno, T., Ueno, A., Shiwa-Sudo, N., Iwata‐Yoshikawa, N., Sakai, Y., Nagata, N., Arashiro, T., Ainai, A., et al. (2023) · iScience · doi:10.1016/j.isci.2023.106694 · Cited by 6 · see citing works
“The vaccination dose interval that affects the induction of cross-neutralizing responses can be considered equivalent to the vaccination-infection interval in breakthrough infections in terms of the time taken for the antibody affinity maturation derived frommemory B cells in germinal centers after mRNA vaccination.(1…”
Plasma EV-miRNAs as Potential Biomarkers of COVID-19 Vaccine Immune Response in Cancer Patients
Almeida, B., Dias, T. R., Cruz, P., Sousa‐Pimenta, M., Teixeira, A. L., Pereira, C. E., Costa‐Silva, B., Oliveira, J., Medeiros, R., & Dias, F. (2024) · Vaccines · doi:10.3390/vaccines12080848 · Cited by 6 · see citing works
Advances and challenges in investigating B-cells via single-cell transcriptomics
Skinner, O. P., Asad, S., & Haque, A. (2024) · Current Opinion in Immunology · doi:10.1016/j.coi.2024.102443 · Cited by 6 · see citing works
Spike-Specific Memory B Cell Response in Hematopoietic Cell Transplantation Recipients following Multiple mRNA-1273 Vaccinations: A Longitudinal Observational Study
Pettini, E., Ciabattini, A., Fiorino, F., et al. (2024) · Vaccines · doi:10.3390/vaccines12040368 · Cited by 4
“Eliciting broad reactive memory B cells is a key aspect in vaccine development, since memory B cells take an important part in the immune response, acting as a secondary defense line and triggering a rapid increase in Ab-secreting plasma cells in case of pathogen exposure ([17]).”
Background
Increased Metabolic Activity of the Thymus and Lymph Nodes in Pediatric Oncology Patients After Coronavirus Disease 2019 Vaccination
Luthria, G., Baratto, L., Adams, L. C., et al. (2023) · Journal of Nuclear Medicine · doi:10.2967/jnumed.123.266271 · Cited by 4 · see citing works
“Recent efforts to understand the immune response to mRNA vaccines revealed germinal center responses in axillary lymph nodes ( 2 ).”
Background
Ultrasound-guided lymph node fine-needle aspiration for evaluating post-vaccination germinal center responses in humans
Scholte, L. L. S., Leggat, D. J., Cohen, K. W., et al. (2023) · STAR Protocols · doi:10.1016/j.xpro.2023.102576 · Cited by 4
Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses than that of the Partially Effective gB/MF59 VaccinePreprint
Hu, X., Karthigeyan, K. P., Herbek, S. L., Valencia, S. M., Jenks, J. A., Webster, H. S., Miller, I. G., Connors, M., Pollara, J., Andy, C., et al. (2023) · medRxiv · doi:10.1101/2023.08.02.23293386 · Cited by 10 · see citing works
“332 The gB/MF59 vaccinees were a lower age range (12-17) than that of mRNA-1647 (18-49) and 333 only female gender, though most vaccinees in the mRNA-1647 cohort were female (76%).”
Background
Prior vaccination enhances immune responses during SARS-CoV-2 breakthrough infection with early activation of memory T cells followed by production of potent neutralizing antibodiesPreprint
Painter, M. M., Johnston, T. S., Lundgreen, K. A., Santos, J. J. D. S., Qin, J. S., Goel, R. R., Apostolidis, S. A., Mathew, D., Fulmer, B., Williams, J. C., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.05.527215 · Cited by 7 · see citing works
“Vaccination also generates long-lasting germinal centers 12, 13 that produce durable and stable populations of memory B cells, including cells capable of cross-binding the highly mutated RBD of Omicron variants 11, 14, 15 .”
Self-citation
A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile
Sannier, G., Nicolas, A., Dubé, M., Marchitto, L., Nayrac, M., Tastet, O., Chatterjee, D., Tauzin, A., Lima-Barbosa, R., Laporte, M., et al. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.100955 · Cited by 6 · see citing works
Germinal Center Response to mRNA Vaccination and Impact of Immunological Imprinting on Subsequent Vaccination
Kim, W. (2024) · Immune Network · doi:10.4110/in.2024.24.e28 · Cited by 5 · see citing works
“Human GC reactions to vaccination were observed in draining axillary lymph nodes for at Human B Cell Responses to SARS-CoV-2 mRNA Vaccination https://doi.org/10.4110/in.2024.24.e28 2/13 https://immunenetwork.org least 6 months following mRNA vaccination (13-17).”
BackgroundInfluential
Enhancing vaccine effectiveness in the elderly to counter antibiotic resistance: The potential of adjuvants via pattern recognition receptors
Jung, M., Kim, H., Choi, E., Shin, M., & Shin, S. J. (2024) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2024.2317439 · Cited by 5 · see citing works
“219,220,288 Certainly, thoughtful consideration from diverse perspectives is imperative in the development or selection of adjuvants for vaccines targeting the elderly in the future.”
Background
Early antiviral CD4 and CD8 T cell responses and antibodies are associated with upper respiratory tract clearance of SARS-CoV-2Preprint
Ramirez, S. I., Lopez, P. G., Faraji, F., Parikh, U. M., Heaps, A., Ritz, J., Moser, C., Eron, J. J., Wohl, D. A., Currier, J. S., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.10.25.564014 · Cited by 3 · see citing works
“Given the biological dependence of the antibody response on CD4 T cell help mediated by T FH cells (51, 52), some statistical association between antibodies and viral load would always be expected, even if, hypothetically, viral control was exclusively mediated by T cells.”
BackgroundSelf-citation
Low switched memory B cells are associated with no humoral response after SARS-CoV-2 vaccine boosters in kidney transplant recipients
Seija, M., García‐Luna, J., Rammauro, F., Brugnini, A., Trías, N., Astesiano, R., Santiago, J., Orihuela, N., Zulberti, C., Machado, D., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1202630 · Cited by 3 · see citing works
Lipid nanoparticles (LNP) induce activation and maturation of antigen presenting cells in young and aged individuals
Connors, J., Joyner, D., Mege, N. J., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-2199652/v1 · Cited by 3
Atypical B cells and impaired SARS-CoV-2 neutralisation following booster vaccination in the elderly.
Ferreira, I., Lee, C. Q., Foster, W., et al. (2022) · medRxiv · doi:10.1101/2022.10.13.22281024 · Cited by 3
Topography of the HLA-A protein enforces shared and convergent immunodominant B cell and antibody alloresponses in transplant recipients
Killian, J. T., King, R. G., Lucander, A. C. K., Kizziah, J. L., Fucile, C., Díaz-Avalos, R., Qiu, S., Silva-Sánchez, A., Mousseau, B. J., Macon, K. J., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.10.014 · Cited by 6 · see citing works
SARS-CoV-2 S protein activates the HIV latent reservoir through the mTOR pathway
Xu, L., Chen, L., Wang, H., et al. (2025) · bioRxiv · doi:10.1101/2025.08.18.670887 · Cited by 2
“When the immune system is stimulated, these latent viruses may be reactivated, leading to HIV replication and transmission [5, 6].”
Impact of Extended Dosing Intervals and Ipsilateral Versus Contralateral Boosting on mRNA Vaccine Immunogenicity in Mice
Lu, B., Chaudhary, O., Banoth, B., Nadkarni, J., Zong, W., Mausser, E., Danz, H., Motwani, M., Ruiz, S., Zhang, D., et al. (2025) · Vaccines · doi:10.3390/vaccines13030263 · Cited by 1 · see citing works
“In contrast, mice immunized with the rHA-AF03 vaccine showed dramatically different antibody response kinetics, with peak GMT titers of 95 [34, 264] and 226 [105, 488] at the 21-day prime–boost interval for the homologous A/Tasmania/503/2020 (H3N2).”
Response to COVID-19 vaccination imaged by PD-L1 PET scanning
MacManus, M. P., Akhurst, T., Lewin, S. R., et al. (2024) · EJNMMI Reports · doi:10.1186/s41824-024-00196-7 · Cited by 2
“…are important for the generation of high-quality spike protein-specific antibodies following COVID-19 mRNA vaccination, and vaccination has been associated with increased intranodal and circulating T follicular helper cells that express high levels of PD-1 (Locci et al. 2013; Lederer et al. 2022).”
Background
SARS-CoV-2 Variants from Long-Term, Persistently Infected Immunocompromised Patients Have Altered Syncytia Formation, Temperature-Dependent Replication, and Serum Neutralizing Antibody Escape
Wouters, C., Sachithanandham, J., Akin, E. H., Pieterse, L., Fall, A., Truong, T., Bard, J. D., Yee, R., Sullivan, D. J., Mostafa, H. H., et al. (2024) · Viruses · doi:10.3390/v16091436 · Cited by 1 · see citing works
“Rapid changes in variant composition within an individual suggest the selection of variants containing certain mutations that promote increased replication ﬁtness, escape from anti-SARS-CoV-2 antibodies or plasma administered thera-peutically, or both [3].”
Background
Antigen-specific CD4+ T cells exhibit distinct transcriptional phenotypes in the lymph node and blood following vaccination in humans
Mudd, P., Borcherding, N., Kim, W., et al. (2023) · Research Square · doi:10.21203/rs.3.rs-3304466/v1 · Cited by 2
Poor immunogenicity upon SARS-CoV-2 mRNA vaccinations in autoimmune SLE patients is associated with pronounced EF-mediated responses and anti-BAFF/Belimumab treatmentPreprint
Faliti, C. E., Anam, F. A., Cheedarla, N., Woodruff, M. C., Usman, S. Y., Runnstrom, M. C., Van, T. T. P., Kyu, S. Y., Ahmed, H., Morrison-Porter, A., et al. (2023) · medRxiv · doi:10.1101/2023.06.08.23291159 · Cited by 4 · see citing works
“FNA has also been used to demonstrate defective GC reactions and memory B cell formation in kidney transplant recipients 63 .”
SARS-CoV-2-specific B cell responses in non-draining lymph nodes and antibody functionalities in immunized end-stage renal disease patients
Frölke, S. C., Geers, D., Amirkhan, K. G., Pathmarajah, D. S., van der Bom‐Baylon, N. D., Idu, M. M., van Gils, M. J., Claireaux, M. A. F., Geerlings, S. E., Rispens, T., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-27815-y · Cited by 1 · see citing works
“It was also stated that human GC responses to COVID-19 vaccines are restricted to draining axillary LNs, from where the vaccine was originally injected, as the contralateral LNs displayed a trend for lower frequencies of GC B-cells that were not SARS-CoV-2-specific 11 .”
Early lymph node T follicular helper cell signalling hub drives influenza vaccine response in an ancestrally diverse cohort
Siu, J. H. Y., Coelho, S., Palomeras, A., Belij‐Rammerstorfer, S., Barman, N., Lee, C. H.-J., Ströbel, T., Thorpe, C. J., Kaur, C., Cole, T., et al. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2025.106036 · Cited by 3 · see citing works
“48,49 Our data show that whilst some non-specific changes occur in the ndLN, the coordinated swelling and adaptive immune cell increase are restricted to draining lymphatic tissue in the week post vaccination.”
The quantity and quality of B-cell immunity against SARS-CoV-2 in children with cancer and hematological diseases
Tiselius, E., Sundberg, E., Amor, A. R., Andersson, H., Varnaite, R., Kolstad, L., Akaberi, D., Ling, J., Harila‐Saari, A. H., Saghafian‐Hedengren, S., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1613778
“We hypothesize that this may be due to a blunted GC reaction caused by immunosuppressive treatment, as has been suggested in immunosuppressed adults (44) where SARS-CoV-2-speci ﬁ c GC B cell populations were strongly associated with the ability to produce SARS-CoV-2 nAbs.”
B-Cell Subset Representation Predicts SARS-CoV-2 Vaccine Response in Solid Organ Transplant Recipients
Knox, J. J., Lee, I., Blumberg, E. A., Rosenfeld, A. M., Meng, W., Liu, F., Kearns, C., O’Doherty, U., Shaked, A. A., Olthoff, K. M., et al. (2025) · The Journal of Infectious Diseases · doi:10.1093/infdis/jiaf250 · Cited by 3 · see citing works
“Prior studies supported our rationale by demonstrating a range of impaired SARS-CoV-2 vaccine–specific B-cell immunity [7, 8] and associating vaccine responsiveness with frequencies of transitional or switched memory B cells (MBCs) in kidney transplant recipients [9, 10].”
Pneumococcal vaccine hyporesponsiveness in people living with HIV: A narrative review of immunological mechanisms and insights from minimally invasive lymph node sampling
Loe-Sack-Sioe, G. E., de Vos, D. W., Visser, L. G., Jochems, S. P., & Roukens, A. H. E. (2025) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2025.2503602 · Cited by 1 · see citing works
Bibliometric and visual analysis of research related to kidney disease and COVID-19
Sun, M., Wang, D., Wu, H., et al. (2025) · Discover medicine · doi:10.1007/s44337-025-00277-x · Cited by 1

Formation of lymph follicles and germinal centers in draining lymph nodes after local injection of phytohemagglutinin and lipopolysaccharide in mice.
HOSHI, H., KAMIYA, K., Takemoto, R., et al. (1984) · Archivum histologicum japonicum · doi:10.1679/aohc.47.505 · Cited by 17 · see citing works
Peritoneal macrophages introduced into mouse foot pads enter the germinal center of regional lymph nodes nonspecifically
Kotani, M., Ezaki, T., Fujii, H., et al. (1979) · Cells Tissues Organs · doi:10.1159/000145092 · Cited by 13 · see citing works
Cutting Edge: IL-21 and TLR Signaling Regulate Germinal Center Responses in a B Cell-Intrinsic Manner
Bessa, J., Köpf, M., & Bachmann, M. F. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903949 · Cited by 139 · see citing works
Quantitatively Reduced Participation of Anti-Nuclear Antigen B Cells That Down-Regulate B Cell Receptor during Primary Development in the Germinal Center/Memory B Cell Response to Foreign Antigen
Alabyev, B., Rahman, Z. S. M., & Manser, T. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5623 · Cited by 18 · see citing works
Transcription Factors IRF8 and PU.1 Are Required for Follicular B Cell Development and BCL6‐driven Germinal Center Responses
Wang, H., Jain, S., Li, P., Lin, J.-X., Oh, J., Qi, C., Gao, Y., Sun, J., Sakai, T., Naghashfar, Z., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1901258116 · Cited by 81 · see citing works

Authors: Lederer, K., Parvathaneni, K., Painter, M. M., Bettini, E., Agarwal, D., Lundgreen, K. A., Weirick, M., Goel, R. R., Xu, X., Drapeau, E. M., Gouma, S., Greenplate, A. R., Coz, C. L., Romberg, N., Jones, L., Rosen, M., Besharatian, B., Kaminiski, M., Weiskopf, D., Sette, A., Hensley, S. E., Bates, P., Wherry, E. J., Naji, A., Bhoj, V., & Locci, M.
Affiliations: University of Pennsylvania (US)
Harvard University (US)
Children's Hospital of Philadelphia (US)
La Jolla Institute for Immunology (US)
Corresponding author: Naji, Ali
Bhoj, Vijay
Locci, Michela
ORCID: Lederer, Katlyn
Parvathaneni, Kalpana
Painter, Mark M.
Bettini, Emily
Agarwal, Divyansh
Lundgreen, Kendall A.
Weirick, Madison
Goel, Rishi R.
Drapeau, Elizabeth M.
Gouma, Sigrid
Greenplate, Allison R.
Coz, Carole Le
Romberg, Neil
Besharatian, Behdad
Weiskopf, Daniela
Sette, Alessandro
Hensley, Scott E.
Bates, Paul
Wherry, E. John
Naji, Ali
Bhoj, Vijay
Locci, Michela
Venue: Cell
Publisher: openRxiv
Published: 2021-09-21
Volume: 185
Issue: 6
Pages: 1008-1024.e15
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1101/2021.09.16.21263686
PMC: PMC8475965
OpenAlex: W4221071417
Cited by: 179
References: 0
Citations by year: 2026: 15 · 2025: 33 · 2024: 33 · 2023: 45 · 2022: 44 · 2021: 9
FWCI: 19.04
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Cell (publishedVersion)
medRxiv (acceptedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Institutional Repository University of Antioquia (University of Antioquia) (publishedVersion, cc-by)
PubMed Central (submittedVersion)
Funders: National Institutes of Health (Nr. 75N9301900065, 75N9301900065)
National Blood Foundation
National Institute of Allergy and Infectious Diseases (R21AI142638, R01AI152236, R01AI146101, R01AI146026, R01AI123738, 75N9301900065, U19AI082630, R01AI153064)
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords: germinal center, COVID-19 mRNA vaccine, immunocompromised patients, kidney transplant recipients, memory B cells, T follicular helper cells, neutralizing antibodies, vaccine-induced immunity, humoral immunity, CD4 and CD8 T cells, lymph node fine needle aspiration

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Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

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