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All Rights Reserved [Search All ] [ ] [ ] Sign In Individual Sign In Sign inCreate an Account Institutional Sign In OpenAthens Shibboleth Purchase Options: Subscribe to the JAMA journal full text icon Full Text contents icon Contents figure icon Figures / Tables multimedia icon Multimedia attach icon Supplemental Content references icon References related icon Related comments icon Comments Download PDF Comment Top of Article * Methods * Results * Discussion * Article Information * References Figure. Neutralizing Antibody Responses Against SARS-CoV-2 Variants View LargeDownload A, Data from 20 patients with acute COVID-19 infection (5-19 days after symptom onset). B, Data from 20 convalescent COVID-19 individuals (32-94 days after symptom onset). C, Data from 14 healthy individuals (aged 18-55 years) who received the Moderna (mRNA-1273) vaccine, 100-mg dose, on day 14 (postsecond dose). The geometric mean titers (GMTs) with 95% CI are shown for samples against the A.1, B.1, B.1.1.7, and N501Y variants. The horizontal dashed lines indicate the limit of detection (FRNT[50] GMT = 20). Statistical significance was determined with the Kruskal-Wallis test to compare GMTs between the variants, followed by the Dunn's multiple comparison post hoc test. For A (acutely infected patients) and B (convalescent individuals), no comparisons were statistically significant. For C (vaccinated individuals), significant differences were found for variant A.1 vs B.1 (P < .001), variant A.1 vs B.1.1.7 (P = .02), and variant A.1 vs N501Y (P = .02). FRNT[50 ]indicates live-virus focus reduction neutralization tests with the reciprocal dilution of serum that neutralizes 50% of the input virus. Supplement. Materials and Methods eReferences 1. Suthar MS, Zimmerman MG, Kauffman RC, et al. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Rep Med. 2020;1(3):100040. doi:10.1016/j.xcrm.2020.100040PubMedGoogle Scholar 2. Jackson LA, Anderson EJ, Rouphael NG, et al; mRNA-1273 Study Group. An mRNA vaccine against SARS-CoV-2. N Engl J Med. 2020;383 (20):1920-1931. doi:10.1056/NEJMoa2022483PubMedGoogle ScholarCrossref 3. Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021;371(6529):eabf4063. doi:10.1126/science.abf4063PubMedGoogle Scholar 4. Widge AT, Rouphael NG, Jackson LA, et al; mRNA-1273 Study Group. Durability of responses after SARS-CoV-2 mRNA-1273 vaccination. N Engl J Med. 2021;384(1):80-82. doi:10.1056/NEJMc2032195PubMedGoogle ScholarCrossref 5. Liu Y, Liu J, Xia H, et al. Neutralizing activity of BNT162b2-elicited serum: preliminary report. N Engl J Med. Published online February 17, 2021. doi:10.1056/NEJMc2102017PubMed Google Scholar 6. Vanderheiden A, Edara VV, Floyd K, et al. Development of a rapid focus reduction neutralization test assay for measuring SARS-CoV-2 neutralizing antibodies. Curr Protoc Immunol. 2020;131(1):e116. doi:10.1002/cpim.116PubMedGoogle Scholar * Change in Donor Characteristics and Antibodies to SARS-CoV-2 in Donated Blood in the US, June-August 2020 Research Letter October 27, 2020 This study describes changes in blood donor demographics and seroreactivity after testing of blood donations for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies began and was publicized in the US in mid-June 2020. Roger Y. Dodd, PhD; Meng Xu, MPH; Susan L. Stramer, PhD * Change in Antibodies to SARS-CoV-2 Among Health Care Personnel in Nashville, Tennessee Research Letter November 3, 2020 This study examines the duration of antibody response to SARS-CoV-2 in health care personnel over a 60-day period in Nashville, Tennessee. Manish M. Patel, MD; Natalie J. Thornburg, PhD; William B. Stubblefield, MD; H. Keipp Talbot, MD, MPH; Melissa M. Coughlin, PhD; Leora R. Feldstein, PhD, MSc; Wesley H. Self, MD, MPH * Health Workers' Antibody Levels Wane After SARS-CoV-2 Infection News From the Centers for Disease Control and Prevention January 12, 2021 Bridget M. Kuehn, MSJ * Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection Original Investigation February 24, 2021 This cohort study evaluates evidence of SARS-CoV-2 infection based on diagnostic nucleic acid amplification test among patients who tested positive versus negative for antibodies. Raymond A. Harvey, MPH; Jeremy A. Rassen, ScD; Carly A. Kabelac, BS; Wendy Turenne, MS; Sandy Leonard, MPH; Reyna Klesh, MS; William A. Meyer III, PhD, D(ABMM), MLS(ASCP)CM; Harvey W. Kaufman, MD, MBA; Steve Anderson, PhD; Oren Cohen, MD; Valentina I. Petkov, MD, MPH; Kathy A. Cronin, PhD; Alison L. Van Dyke, MD, PhD; Douglas R. Lowy, MD; Norman E. Sharpless, MD; Lynne T. Penberthy, MD, MPH * Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2 Research Letter March 1, 2021 This study compares titers of binding and neutralizing antibodies after a single mRNA coronavirus vaccine dose in health care workers previously infected with SARS-CoV-2. Saman Saadat, PhD; Zahra Rikhtegaran Tehrani, PhD; James Logue, BS; Michelle Newman, BSN; Matthew B. Frieman, PhD; Anthony D. Harris, MD; Mohammad M. 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The following information is required and must be completed in order to submit a comment: Thank You. Your comment submission was successful. Please allow up to 2 business days for review, approval, and posting. JAMA 1 Comment for this article March 20, 2021 Cellular Response Paz Einat, Ph.D. | Dr. Paz Einat Biotechnology Projects & Consulting This Research Letter makes no mention of cellular response. T-cells comprise an essential part of the immune response, they potentially are less prone to decreased efficacy due to mutations and, while they are much more difficult to examine, the minimum is to address this part of the immune system in the discussion. CONFLICT OF INTEREST: None Reported New Online Views 48,981 Citations 0 Comments 1 View Metrics * Download PDF * Twitter Facebook More Email LinkedIn * Cite This Citation Edara VV, Hudson WH, Xie X, Ahmed R, Suthar MS. Neutralizing Antibodies Against SARS-CoV-2 Variants After Infection and Vaccination. JAMA. Published online March 19, 2021. doi:10.1001/ jama.2021.4388 Download citation file: Ris (Zotero) EndNote BibTex Medlars ProCite RefWorks Reference Manager Mendeley (c) 2021 * Permissions Research Letter March 19, 2021 Neutralizing Antibodies Against SARS-CoV-2 Variants After Infection and Vaccination Venkata Viswanadh Edara, PhD^1; William H. Hudson, PhD^2; Xuping Xie, PhD^3; et al Rafi Ahmed, PhD^2; Mehul S. Suthar, PhD^1 Author Affiliations Article Information * ^1Emory University Department of Pediatrics, Atlanta, Georgia * ^2Emory Vaccine Center, Atlanta, Georgia * ^3University of Texas Medical Branch, Galveston JAMA. Published online March 19, 2021. doi:10.1001/jama.2021.4388 visual abstract icon Visual Abstract editorial comment icon Editorial Comment related articles icon Related Articles author interview icon Interviews multimedia icon Multimedia * Research Letter Change in Donor Characteristics and Antibodies to SARS-CoV-2 in Donated Blood in the US, June-August 2020 Roger Y. Dodd, PhD; Meng Xu, MPH; Susan L. Stramer, PhD * Research Letter Change in Antibodies to SARS-CoV-2 Among Health Care Personnel in Nashville, Tennessee Manish M. Patel, MD; Natalie J. Thornburg, PhD; William B. Stubblefield, MD; H. Keipp Talbot, MD, MPH; Melissa M. Coughlin, PhD; Leora R. Feldstein, PhD, MSc; Wesley H. Self, MD, MPH * News From the Centers for Disease Control and Prevention Health Workers' Antibody Levels Wane After SARS-CoV-2 Infection Bridget M. Kuehn, MSJ * Original Investigation Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection Raymond A. Harvey, MPH; Jeremy A. Rassen, ScD; Carly A. Kabelac, BS; Wendy Turenne, MS; Sandy Leonard, MPH; Reyna Klesh, MS; William A. Meyer III, PhD, D(ABMM), MLS(ASCP)CM; Harvey W. Kaufman, MD, MBA; Steve Anderson, PhD; Oren Cohen, MD; Valentina I. Petkov, MD, MPH; Kathy A. Cronin, PhD; Alison L. Van Dyke, MD, PhD; Douglas R. Lowy, MD; Norman E. Sharpless, MD; Lynne T. Penberthy, MD, MPH * Research Letter Antibody Titers After a Single Vaccine Dose in Health Care Workers Previously Infected With SARS-CoV-2 Saman Saadat, PhD; Zahra Rikhtegaran Tehrani, PhD; James Logue, BS; Michelle Newman, BSN; Matthew B. Frieman, PhD; Anthony D. Harris, MD; Mohammad M. Sajadi, MD Serum neutralizing antibodies rapidly appear after SARS-CoV-2 infection^1 and vaccination^2 and are maintained for several months.^ 3^,4 The emergence of SARS-CoV-2 variants has raised concerns about the breadth of neutralizing-antibody responses. We compared the neutralizing-antibody response to 4 variants in infected and vaccinated individuals to determine how mutations within the spike protein are associated with virus neutralization. Methods Serum samples were obtained from 3 groups of individuals. At Emory University, hospitalized adults with SARS-CoV-2 infection (polymerase chain reaction confirmed) were enrolled 5 to 19 days after symptom onset (July 2020). Infected convalescent individuals (polymerase chain reaction or antigen test confirmed) were enrolled 32 to 94 days after symptom onset (March to August 2020). Deidentified serum samples drawn 14 days after the second dose (100-mg cohort) from individuals in the mRNA-1273 phase 1 clinical trial^2 were obtained from the National Institutes of Health. See the eAppendix in the Supplement for participant details. Institutional review board approval was obtained from Emory University and Advarra; all participants provided written informed consent. Four variants were examined, chosen to represent the original SARS-CoV-2 strain and emerging variants with mutations in the spike protein. The first variant, nCoV/USA_WA1/2020 (A.1 lineage), closely resembled the original Wuhan strain and the spike used in the mRNA-1273 vaccine, and was propagated from an infectious SARS-CoV-2 clone. The second variant, EHC-083E (B.1 lineage), containing a D614G mutation within the spike, was the predominant circulating strain at the time of the study and was isolated from a residual nasopharyngeal swab from a patient in Atlanta, Georgia, in March 2020 (SARS-CoV-2/ human/USA/GA-EHC-083E/2020). The third variant, B.1.1.7 (SARS-CoV-2/ human/USA/CA_CDC_5574/2020), was originally identified in the UK and of concern because of increased transmissibility. It contained several spike mutations and was isolated from a residual nasopharyngeal swab from a patient in San Diego, California, in December 2020. The fourth variant, N501Y SARS-CoV-2 virus, containing a mutation in the critical receptor binding domain of the spike that is present across multiple emerging variants, including the B.1.1.7 variant in this study, was generated from an infectious clone as previously described.^5 This virus is not found in nature. Live-virus focus reduction neutralization tests (FRNTs) were performed as previously described.^6 See the eAppendix in the Supplement for details on the laboratory methods. FRNT[50] titers, which represent the reciprocal dilution of serum that neutralizes 50% of the input virus, were interpolated with a 4-parameter nonlinear regression, and geometric mean titers (GMTs) were calculated with 95% CI in GraphPad Prism version 8.4.3. Kruskal-Wallis test was used to compare FRNT[50] GMTs between the variants, followed by Dunn's multiple comparison post hoc test. We determined P < .05 (2 sided) to define statistical significance. Results Twenty acutely infected COVID-19 patients provided serum samples (mean age, 56.6 years; 50% men). The FRNT[50] GMT for the A.1 variant was 186 (95% CI, 90-383); for B.1, 110 (95% CI, 57-209); for B.1.1.7, 116 (95% CI, 62-215); and for N501Y, 141 (95% CI, 74-269). Comparison of the FRNT[50] GMT of the variants was not statistically significant (Figure). Twenty convalescent individuals provided serum samples (mean age, 45 years; 55% men). The FRNT[50] GMT for the A.1 variant was 168 (95% CI, 113-249); for B.1, 91 (95% CI, 60-138); for B.1.1.7, 145 (95% CI, 96-220); and for N501Y, 145 (95% CI, 76-172). Comparison of the FRNT [50] GMT of the variants was not statistically significant. Serum samples were available for 14 mRNA-1273 vaccinated individuals^ 2 (age range, 18-55 years; 43% men). The FRNT[50] GMT for the A.1 variant was 1709 (95% CI, 1412-2069); for B.1, 804 (95% CI, 632-1023); for B.1.1.7, 965 (95% CI, 695-1341); and for N501Y, 994 (95% CI, 777-1272). Comparisons of the FRNT[50] GMT of B.1, B.1.1.7, and the N501Y variant were not statistically significant. The FRNT [50] GMTs for the B.1 (P < .001), B.1.1.7 (P = .02), and N501Y (P = .02) variants were statistically significantly lower than that for the A.1 variant. Discussion This study found neutralizing activity of infection- and vaccine-elicited antibodies against 4 SARS-CoV-2 variants, including B.1, B.1.1.7, and N501Y. Because neutralization studies measure the ability of antibodies to block virus infection, these results suggest that infection- and vaccine-induced immunity may be retained against the B.1.1.7 variant. As additional variants emerge, neutralizing-antibody responses after infection and vaccination should be monitored. Limitations include the small sample size, possible selection bias, lack of clinical outcomes, and how neutralization titers correlate with protection. Section Editor: Jody W. Zylke, MD, Deputy Editor. Back to top Article Information Corresponding Author: Mehul S. Suthar, PhD, Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd, Room 2022, Atlanta, GA 30329-4208 (msuthar@emory.edu). Accepted for Publication: March 8, 2021. Published Online: March 19, 2021. doi:10.1001/jama.2021.4388 Author Contributions: Dr Suthar had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Edara, Ahmed, Suthar. Acquisition, analysis, or interpretation of data: Edara, Hudson, Xie, Suthar. Drafting of the manuscript: Edara, Suthar. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Edara, Hudson, Suthar. Obtained funding: Suthar. Administrative, technical, or material support: Xie, Suthar. Supervision: Edara, Ahmed, Suthar. Data visualization: Hudson. Conflict of Interest Disclosures: None reported. Funding/Support: This work was supported in part by grants NIH P51 OD011132, 3U19AI057266-17S1 CCHI Immune Memory Supplement, U19AI090023, R01AI127799, R01AI148378, K99AI153736, and UM1AI148684 to Emory University; R00AG049092 and R24AI120942 to the University of Texas Medical Branch from the National Institute of Allergy and Infectious Diseases, National Institutes of Health; the Oliver S. and Jennie R. Donaldson Charitable Trust; the Emory Executive Vice President for Health Affairs Synergy Fund award; the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children's Healthcare of Atlanta; COVID-Catalyst-I^3 Funds from the Woodruff Health Sciences Center and Emory School of Medicine; Woodruff Health Sciences Center 2020 COVID-19 CURE Award; and the Vital Projects/Proteus funds. Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Additional Contributions: We acknowledge the following individuals for providing reagents, discussion, and editing of the manuscript: Emory University School of Medicine, Atlanta, Georgia: Katharine Floyd, BS, Lilin Lai, MD, Meredith Gardner, PhD, Anne Piantadosi, MD, Jesse J. Waggoner, MD, Ahmed Babiker, MBBS, David S. Stephens, MD, Evan J. Anderson, MD, Srilatha Edupuganti, MD, MPH, Nadine Rouphael, MD, MSc, Grace Mantus, MS, Lindsay Nyhoff, PhD, Jens Wrammert, PhD, Max W. Adelman, MD, MSc, Rebecca Fineman, BS, Shivan Patel, MD, Rebecca Byram, ME, Dumingu Nipuni Gomes, MPH, Garett Michael, BS, BA, Hayatu Abdullahi, MD, Erin M. Scherer, PhD, Nour Beydoun, MD, Bernadine Panganiban, BS, Nina McNair, BS, Kieffer Hellmeister, BA, Jamila Pitts, BS, Joy Winters, MS, Jennifer Kleinhenz, BS, Jacob Usher, BS, and James O'Keefe, MD; UC San Diego School of Medicine, California: Louise C. Laurent, MD, PhD, Peter De Hoff, PhD, Holly Valentine, BA, MPH, Rob Knight, PhD, Phoebe Seaver, BA, MPH, Gene W. Yeo, PhD, MBA, Shashank Sathe, BTech, MS, and Aaron Carlin, MD, PhD; The Scripps Research Institute, La Jolla, California: Kristian G. Andersen, PhD, Mark Zeller, PhD, Karthik Gangavarapu, BS, Catie Anderson, BA, and Alaa Abdel Latif, BA, MPhil, BS; University of Texas Medical Branch, Galveston: Kumari Lokugamage, PhD, Vineet Menachery, PhD, Pei-Yong Shi, PhD; and Centers for Disease Control and Prevention, Atlanta, Georgia: Natalie Thornburg, PhD, Azaibi Tamin, PhD, Jennifer L. Harcourt, PhD, Maureen Diaz, PhD, Suxiang Tong, PhD, Ying Tao, PhD, Jing Zhang, PhD, Phili Wong, MS, Shilpli Jain, PhD, and Jennifer Folster, PhD. No one received financial compensation for his or her contributions. We thank the mRNA-1273 phase 1 study team and the Division of Microbiology and Infectious Diseases for providing clinical samples. References 1. Suthar MS, Zimmerman MG, Kauffman RC, et al. Rapid generation of neutralizing antibody responses in COVID-19 patients. Cell Rep Med. 2020;1(3):100040. doi:10.1016/j.xcrm.2020.100040PubMedGoogle Scholar 2. Jackson LA, Anderson EJ, Rouphael NG, et al; mRNA-1273 Study Group. An mRNA vaccine against SARS-CoV-2. N Engl J Med. 2020;383 (20):1920-1931. doi:10.1056/NEJMoa2022483PubMedGoogle ScholarCrossref 3. Dan JM, Mateus J, Kato Y, et al. Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection. Science. 2021;371(6529):eabf4063. doi:10.1126/science.abf4063PubMedGoogle Scholar 4. Widge AT, Rouphael NG, Jackson LA, et al; mRNA-1273 Study Group. Durability of responses after SARS-CoV-2 mRNA-1273 vaccination. N Engl J Med. 2021;384(1):80-82. doi:10.1056/NEJMc2032195PubMedGoogle ScholarCrossref 5. Liu Y, Liu J, Xia H, et al. Neutralizing activity of BNT162b2-elicited serum: preliminary report. N Engl J Med. Published online February 17, 2021. doi:10.1056/NEJMc2102017PubMed Google Scholar 6. Vanderheiden A, Edara VV, Floyd K, et al. Development of a rapid focus reduction neutralization test assay for measuring SARS-CoV-2 neutralizing antibodies. 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