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Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination.
Sci Immunol. 2021 04 15; 6(58)SI

Abstract

Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting.

Authors+Show Affiliations

Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Division of Rheumatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Parker Institute for Cancer Immunotherapy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Department of Microbiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.Institute for Immunology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. wherry@pennmedicine.upenn.edu. Immune Health™, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Parker Institute for Cancer Immunotherapy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33858945

Citation

Goel, Rishi R., et al. "Distinct Antibody and Memory B Cell Responses in SARS-CoV-2 Naïve and Recovered Individuals Following mRNA Vaccination." Science Immunology, vol. 6, no. 58, 2021.
Goel RR, Apostolidis SA, Painter MM, et al. Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Sci Immunol. 2021;6(58).
Goel, R. R., Apostolidis, S. A., Painter, M. M., Mathew, D., Pattekar, A., Kuthuru, O., Gouma, S., Hicks, P., Meng, W., Rosenfeld, A. M., Dysinger, S., Lundgreen, K. A., Kuri-Cervantes, L., Adamski, S., Hicks, A., Korte, S., Oldridge, D. A., Baxter, A. E., Giles, J. R., ... Wherry, E. J. (2021). Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Science Immunology, 6(58). https://doi.org/10.1126/sciimmunol.abi6950
Goel RR, et al. Distinct Antibody and Memory B Cell Responses in SARS-CoV-2 Naïve and Recovered Individuals Following mRNA Vaccination. Sci Immunol. 2021 04 15;6(58) PubMed PMID: 33858945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. AU - Goel,Rishi R, AU - Apostolidis,Sokratis A, AU - Painter,Mark M, AU - Mathew,Divij, AU - Pattekar,Ajinkya, AU - Kuthuru,Oliva, AU - Gouma,Sigrid, AU - Hicks,Philip, AU - Meng,Wenzhao, AU - Rosenfeld,Aaron M, AU - Dysinger,Sarah, AU - Lundgreen,Kendall A, AU - Kuri-Cervantes,Leticia, AU - Adamski,Sharon, AU - Hicks,Amanda, AU - Korte,Scott, AU - Oldridge,Derek A, AU - Baxter,Amy E, AU - Giles,Josephine R, AU - Weirick,Madison E, AU - McAllister,Christopher M, AU - Dougherty,Jeanette, AU - Long,Sherea, AU - D'Andrea,Kurt, AU - Hamilton,Jacob T, AU - Betts,Michael R, AU - Luning Prak,Eline T, AU - Bates,Paul, AU - Hensley,Scott E, AU - Greenplate,Allison R, AU - Wherry,E John, PY - 2021/03/26/received PY - 2021/04/12/accepted PY - 2021/4/16/entrez PY - 2021/4/17/pubmed PY - 2021/4/27/medline JF - Science immunology JO - Sci Immunol VL - 6 IS - 58 N2 - Novel mRNA vaccines for SARS-CoV-2 have been authorized for emergency use. Despite their efficacy in clinical trials, data on mRNA vaccine-induced immune responses are mostly limited to serological analyses. Here, we interrogated antibody and antigen-specific memory B cells over time in 33 SARS-CoV-2 naïve and 11 SARS-CoV-2 recovered subjects. SARS-CoV-2 naïve individuals required both vaccine doses for optimal increases in antibodies, particularly for neutralizing titers against the B.1.351 variant. Memory B cells specific for full-length spike protein and the spike receptor binding domain (RBD) were also efficiently primed by mRNA vaccination and detectable in all SARS-CoV-2 naive subjects after the second vaccine dose, though the memory B cell response declined slightly with age. In SARS-CoV-2 recovered individuals, antibody and memory B cell responses were significantly boosted after the first vaccine dose; however, there was no increase in circulating antibodies, neutralizing titers, or antigen-specific memory B cells after the second dose. This robust boosting after the first vaccine dose strongly correlated with levels of pre-existing memory B cells in recovered individuals, identifying a key role for memory B cells in mounting recall responses to SARS-CoV-2 antigens. Together, our data demonstrated robust serological and cellular priming by mRNA vaccines and revealed distinct responses based on prior SARS-CoV-2 exposure, whereby COVID-19 recovered subjects may only require a single vaccine dose to achieve peak antibody and memory B cell responses. These findings also highlight the utility of defining cellular responses in addition to serologies and may inform SARS-CoV-2 vaccine distribution in a resource-limited setting. SN - 2470-9468 UR - https://www.unboundmedicine.com/medline/citation/33858945/Distinct_antibody_and_memory_B_cell_responses_in_SARS_CoV_2_naïve_and_recovered_individuals_following_mRNA_vaccination_ L2 - https://immunology.sciencemag.org/cgi/pmidlookup?view=long&pmid=33858945 DB - PRIME DP - Unbound Medicine ER -