{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T08:16:16Z","timestamp":1780992976097,"version":"3.54.1"},"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011221","name":"School of Medicine, University of Alabama at Birmingham","doi-asserted-by":"publisher","award":["COVID-19 Research Initiative"],"award-info":[{"award-number":["COVID-19 Research Initiative"]}],"id":[{"id":"10.13039\/100011221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011221","name":"School of Medicine, University of Alabama at Birmingham","doi-asserted-by":"publisher","award":["COVID-19 Research Initiative"],"award-info":[{"award-number":["COVID-19 Research Initiative"]}],"id":[{"id":"10.13039\/100011221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011221","name":"School of Medicine, University of Alabama at Birmingham","doi-asserted-by":"publisher","award":["COVID-19 Research Initiative"],"award-info":[{"award-number":["COVID-19 Research Initiative"]}],"id":[{"id":"10.13039\/100011221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011221","name":"School of Medicine, University of Alabama at Birmingham","doi-asserted-by":"publisher","award":["Cancer Immunobiology Program"],"award-info":[{"award-number":["Cancer Immunobiology Program"]}],"id":[{"id":"10.13039\/100011221","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI069452"],"award-info":[{"award-number":["UM1AI069452"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI150590"],"award-info":[{"award-number":["R01AI150590"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["U01CA260462"],"award-info":[{"award-number":["U01CA260462"]}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Patients with chronic lymphocytic leukemia (CLL) have reduced seroconversion rates and lower binding antibody (Ab) and neutralizing antibody (NAb) titers than healthy individuals following Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccination. Here, we dissected vaccine-mediated humoral and cellular responses to understand the mechanisms underlying CLL-induced immune dysfunction.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>We performed a prospective observational study in SARS-CoV-2 infection-na\u00efve CLL patients (<jats:italic>n<\/jats:italic> = 95) and healthy controls (<jats:italic>n<\/jats:italic> = 30) who were vaccinated between December 2020 and June 2021. Sixty-one CLL patients and 27 healthy controls received 2 doses of the Pfizer-BioNTech BNT162b2 vaccine, while 34 CLL patients and 3 healthy controls received 2 doses of the Moderna mRNA-1273 vaccine. The median time to analysis was 38 days (IQR, 27 to 83) for CLL patients and 36 days (IQR, 28 to 57) for healthy controls. Testing plasma samples for SARS-CoV-2 anti-spike and receptor-binding domain Abs by enzyme-linked immunosorbent assay (ELISA), we found that all healthy controls seroconverted to both antigens, while CLL patients had lower response rates (68% and 54%) as well as lower median titers (23-fold and 30-fold; both <jats:italic>p<\/jats:italic> &lt; 0.001). Similarly, NAb responses against the then prevalent D614G and Delta SARS-CoV-2 variants were detected in 97% and 93% of controls, respectively, but in only 42% and 38% of CLL patients, who also exhibited &gt;23-fold and &gt;17-fold lower median NAb titers (both <jats:italic>p<\/jats:italic> &lt; 0.001). Interestingly, 26% of CLL patients failed to develop NAbs but had high-titer binding Abs that preferentially reacted with the S2 subunit of the SARS-CoV-2 spike. Since these patients were also seropositive for endemic human coronaviruses (HCoVs), these responses likely reflect cross-reactive HCoV Abs rather than vaccine-induced de novo responses. CLL disease status, advanced Rai stage (III-IV), elevated serum beta-2 microglobulin levels (\u03b22m &gt;2.4 mg\/L), prior therapy, anti-CD20 immunotherapy (&lt;12 months), and intravenous immunoglobulin (IVIg) prophylaxis were all predictive of an inability to mount SARS-CoV-2 NAbs (all <jats:italic>p<\/jats:italic> \u2264 0.03). T cell response rates determined for a subset of participants were 2.8-fold lower for CLL patients compared to healthy controls (0.05, 95% CI 0.01 to 0.27, <jats:italic>p<\/jats:italic> &lt; 0.001), with reduced intracellular IFN\u03b3 staining (<jats:italic>p<\/jats:italic> = 0.03) and effector polyfunctionality (<jats:italic>p<\/jats:italic> &lt; 0.001) observed in CD4<jats:sup>+<\/jats:sup> but not in CD8<jats:sup>+<\/jats:sup> T cells. Surprisingly, in treatment-na\u00efve CLL patients, BNT162b2 vaccination was identified as an independent negative risk factor for NAb generation (5.8, 95% CI 1.6 to 27, <jats:italic>p<\/jats:italic> = 0.006). CLL patients who received mRNA-1273 had 12-fold higher (<jats:italic>p<\/jats:italic> &lt; 0.001) NAb titers and 1.7-fold higher (6.5, 95% CI 1.3 to 32, <jats:italic>p<\/jats:italic> = 0.02) response rates than BNT162b2 vaccinees despite similar disease characteristics. The absence of detectable NAbs in CLL patients was associated with reduced na\u00efve CD4<jats:sup>+<\/jats:sup> T cells (<jats:italic>p<\/jats:italic> = 0.03) and increased CD8<jats:sup>+<\/jats:sup> effector memory T cells (<jats:italic>p<\/jats:italic> = 0.006). Limitations of the study were that not all participants were subjected to the same immune analyses and that pre-vaccination samples were not available.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>CLL pathogenesis is characterized by a progressive loss of adaptive immune functions, including in most treatment-na\u00efve patients, with preexisting memory being preserved longer than the capacity to mount responses to new antigens. In addition, higher NAb titers and response rates identify mRNA-1273 as a superior vaccine for CLL patients.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1004157","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T17:48:41Z","timestamp":1688060921000},"page":"e1004157","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Exposure of progressive immune dysfunction by SARS-CoV-2 mRNA vaccination in patients with chronic lymphocytic leukemia: A prospective cohort study"],"prefix":"10.1371","volume":"20","author":[{"given":"Kai","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhito","family":"Honjo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Sherrill-Mix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weimin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina M.","family":"Stoltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allisa K.","family":"Oman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3582-6462","authenticated-orcid":true,"given":"Lucinda A.","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sterrett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen R.","family":"Frederick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Lancaster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-0533","authenticated-orcid":true,"given":"Mayur","family":"Narkhede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitkumar","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foluso J.","family":"Ogunsile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9048-312X","authenticated-orcid":true,"given":"Rima B.","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Ketas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor M.","family":"Cruz Portillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Cupo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-7206","authenticated-orcid":true,"given":"Benjamin M.","family":"Larimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8142-0386","authenticated-orcid":true,"given":"Anju","family":"Bansal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Goepfert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice H.","family":"Hahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1906-8219","authenticated-orcid":true,"given":"Randall S.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"pmed.1004157.ref001","unstructured":"SEER. Surveillance, Epidemiology, and End Results (SEER) Program. 2014\u20132018. https:\/\/seer.cancer.gov\/statfacts\/html\/clyl.html. Access date 01 November 2022."},{"issue":"5","key":"pmed.1004157.ref002","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1182\/blood-2015-03-567388","article-title":"Perturbation of the normal immune system in patients with CLL","volume":"126","author":"F Forconi","year":"2015","journal-title":"Blood"},{"issue":"25","key":"pmed.1004157.ref003","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL","volume":"131","author":"M Hallek","year":"2018","journal-title":"Blood"},{"issue":"12","key":"pmed.1004157.ref004","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1001\/jamaoncol.2016.2437","article-title":"Seasonal Influenza Vaccination in Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib","volume":"2","author":"C Sun","year":"2016","journal-title":"JAMA Oncol"},{"issue":"10","key":"pmed.1004157.ref005","doi-asserted-by":"crossref","first-page":"e397","DOI":"10.3324\/haematol.2017.164285","article-title":"Ibrutinib may impair serological responses to influenza vaccination","volume":"102","author":"AP Douglas","year":"2017","journal-title":"Haematologica"},{"issue":"25","key":"pmed.1004157.ref006","doi-asserted-by":"crossref","first-page":"3701","DOI":"10.1016\/j.vaccine.2018.05.012","article-title":"Pneumococcal conjugate vaccine triggers a better immune response than pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia A randomized study by the Swedish CLL group","volume":"36","author":"T Svensson","year":"2018","journal-title":"Vaccine"},{"issue":"3","key":"pmed.1004157.ref007","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41375-020-0884-z","article-title":"Response to the conjugate pneumococcal vaccine (PCV13) in patients with chronic lymphocytic leukemia (CLL)","volume":"35","author":"FR Mauro","year":"2021","journal-title":"Leukemia"},{"issue":"2","key":"pmed.1004157.ref008","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1182\/blood.2020008758","article-title":"Effect of Bruton tyrosine kinase inhibitor on efficacy of adjuvanted recombinant hepatitis B and zoster vaccines","volume":"137","author":"C Pleyer","year":"2021","journal-title":"Blood"},{"issue":"6","key":"pmed.1004157.ref009","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1111\/ejh.13223","article-title":"Current clinical practice and challenges in the management of secondary immunodeficiency in hematological malignancies","volume":"102","author":"IK Na","year":"2019","journal-title":"Eur J Haematol"},{"issue":"5","key":"pmed.1004157.ref010","doi-asserted-by":"crossref","DOI":"10.3390\/v14051095","article-title":"Dating the Emergence of Human Endemic Coronaviruses","volume":"14","author":"D Forni","year":"2022","journal-title":"Viruses"},{"issue":"11","key":"pmed.1004157.ref011","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1038\/s41591-020-1083-1","article-title":"Seasonal coronavirus protective immunity is short-lasting","volume":"26","author":"AWD Edridge","year":"2020","journal-title":"Nat Med"},{"issue":"5","key":"pmed.1004157.ref012","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S1473-3099(20)30120-1","article-title":"An interactive web-based dashboard to track COVID-19 in real time","volume":"20","author":"E Dong","year":"2020","journal-title":"Lancet Infect Dis"},{"issue":"2","key":"pmed.1004157.ref013","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/cid\/ciaa863","article-title":"COVID-19 in Immunocompromised Hosts: What We Know So Far","volume":"72","author":"M Fung","year":"2021","journal-title":"Clin Infect Dis"},{"key":"pmed.1004157.ref014","volume-title":"Features, Evaluation, and Treatment of Coronavirus (COVID-19)","author":"M Cascella","year":"2023"},{"issue":"10","key":"pmed.1004157.ref015","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1182\/blood.2020006965","article-title":"Outcomes of COVID-19 in patients with CLL: a multicenter international experience","volume":"136","author":"AR Mato","year":"2020","journal-title":"Blood"},{"issue":"12","key":"pmed.1004157.ref016","doi-asserted-by":"crossref","first-page":"3444","DOI":"10.1038\/s41375-021-01450-8","article-title":"COVID-19 severity and mortality in patients with CLL: an update of the international ERIC and Campus CLL study","volume":"35","author":"T Chatzikonstantinou","year":"2021","journal-title":"Leukemia"},{"key":"pmed.1004157.ref017","unstructured":"COVID PS. COVID-19 Vaccines for Moderately or Severely Immunocompromised People. https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/vaccines\/recommendations\/immuno.html. Access date 24 March 2023."},{"key":"pmed.1004157.ref018","unstructured":"PAXLOVID (Nirmatrelvir Tablets; Ritonavir Tablets) Highlights of Emergency Use Authorization. 2021. https:\/\/www.fda.gov\/media\/155050\/download. Access date 24 March 2023."},{"key":"pmed.1004157.ref019","unstructured":"EVUSHELD (Tixagevimab Co-packaged with Cilgavimab) Highlights of Emergency Use Authorization. 2022. https:\/\/www.fda.gov\/media\/154701\/download. Access date 24 March 2023."},{"key":"pmed.1004157.ref020","unstructured":"VEKLURY (Remdesivir) Highlights of Prescribing Information. 2022. https:\/\/www.gilead.com\/-\/media\/files\/pdfs\/medicines\/covid-19\/veklury\/veklury_pi.pdf. Access date 24 March 2023."},{"issue":"1","key":"pmed.1004157.ref021","doi-asserted-by":"crossref","first-page":"100164","DOI":"10.1016\/j.xcrm.2020.100164","article-title":"Convalescent plasma-mediated resolution of COVID-19 in a patient with humoral immunodeficiency","volume":"2","author":"K Honjo","year":"2021","journal-title":"Cell Rep Med"},{"issue":"5","key":"pmed.1004157.ref022","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1182\/blood.2022016147","article-title":"Patients with CLL have a lower risk of death from COVID-19 in the Omicron era","volume":"140","author":"CU Niemann","year":"2022","journal-title":"Blood"},{"issue":"2","key":"pmed.1004157.ref023","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein","volume":"181","author":"AC Walls","year":"2020","journal-title":"Cell"},{"issue":"2","key":"pmed.1004157.ref024","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"M Hoffmann","year":"2020","journal-title":"Cell"},{"issue":"7","key":"pmed.1004157.ref025","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1016\/j.cell.2020.10.049","article-title":"Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer","volume":"183","author":"VA Avanzato","year":"2020","journal-title":"Cell"},{"issue":"12","key":"pmed.1004157.ref026","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/s41551-020-00660-2","article-title":"Neutralizing antibodies for the treatment of COVID-19","volume":"4","author":"S Jiang","year":"2020","journal-title":"Nat Biomed Eng"},{"issue":"6576","key":"pmed.1004157.ref027","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1126\/science.abm3425","article-title":"Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial","volume":"375","author":"PB Gilbert","year":"2022","journal-title":"Science"},{"issue":"7","key":"pmed.1004157.ref028","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1038\/s41591-021-01377-8","article-title":"Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection","volume":"27","author":"DS Khoury","year":"2021","journal-title":"Nat Med"},{"issue":"5","key":"pmed.1004157.ref029","doi-asserted-by":"crossref","first-page":"e1003991","DOI":"10.1371\/journal.pmed.1003991","article-title":"Antibody responses against SARS-CoV-2 variants induced by four different SARS-CoV-2 vaccines in health care workers in the Netherlands: A prospective cohort study","volume":"19","author":"MJ van Gils","year":"2022","journal-title":"PLoS Med"},{"issue":"23","key":"pmed.1004157.ref030","doi-asserted-by":"crossref","first-page":"3165","DOI":"10.1182\/blood.2021011568","article-title":"Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia","volume":"137","author":"Y Herishanu","year":"2021","journal-title":"Blood"},{"issue":"8","key":"pmed.1004157.ref031","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.ccell.2021.07.012","article-title":"Antibody response to SARS-CoV-2 vaccines in patients with hematologic malignancies","volume":"39","author":"LM Greenberger","year":"2021","journal-title":"Cancer Cell"},{"issue":"4","key":"pmed.1004157.ref032","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.3324\/haematol.2021.280300","article-title":"T-cell immune responses following vaccination with mRNA BNT162b2 against SARS-CoV-2 in patients with chronic lymphocytic leukemia: results from a prospective open-label clinical trial","volume":"107","author":"L Blixt","year":"2022","journal-title":"Haematologica"},{"issue":"2","key":"pmed.1004157.ref033","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1038\/s41375-021-01500-1","article-title":"SARS-CoV-2 specific cellular response following COVID-19 vaccination in patients with chronic lymphocytic leukemia","volume":"36","author":"SC Mellinghoff","year":"2022","journal-title":"Leukemia"},{"issue":"2","key":"pmed.1004157.ref034","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1182\/blood.2020009966","article-title":"Vaccinations in CLL: implications for COVID-19","volume":"137","author":"M Shadman","year":"2021","journal-title":"Blood"},{"issue":"7","key":"pmed.1004157.ref035","doi-asserted-by":"crossref","first-page":"e1009761","DOI":"10.1371\/journal.ppat.1009761","article-title":"SARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence","volume":"17","author":"S Boppana","year":"2021","journal-title":"PLoS Pathog"},{"issue":"8","key":"pmed.1004157.ref036","doi-asserted-by":"crossref","DOI":"10.1128\/JCM.00941-20","article-title":"Performance Characteristics of the Abbott Architect SARS-CoV-2 IgG Assay and Seroprevalence in Boise, Idaho","volume":"58","author":"A Bryan","year":"2020","journal-title":"J Clin Microbiol"},{"issue":"1","key":"pmed.1004157.ref037","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/sj.leu.2404457","article-title":"ERIC recommendations on IGHV gene mutational status analysis in chronic lymphocytic leukemia","volume":"21","author":"P Ghia","year":"2007","journal-title":"Leukemia"},{"issue":"1","key":"pmed.1004157.ref038","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1182\/blood.V98.1.181","article-title":"CD38 expression as an important prognostic factor in B-cell chronic lymphocytic leukemia","volume":"98","author":"S Ibrahim","year":"2001","journal-title":"Blood"},{"issue":"26","key":"pmed.1004157.ref039","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1056\/NEJM200012283432602","article-title":"Genomic aberrations and survival in chronic lymphocytic leukemia","volume":"343","author":"H Dohner","year":"2000","journal-title":"N Engl J Med"},{"issue":"6504","key":"pmed.1004157.ref040","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1126\/science.abc5902","article-title":"Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability","volume":"369","author":"PJM Brouwer","year":"2020","journal-title":"Science"},{"issue":"1","key":"pmed.1004157.ref041","doi-asserted-by":"crossref","first-page":"116","DOI":"10.20411\/pai.v6i1.441","article-title":"Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva","volume":"6","author":"TJ Ketas","year":"2021","journal-title":"Pathog Immun"},{"issue":"9","key":"pmed.1004157.ref042","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.3201\/eid2709.211042","article-title":"Predictors of Nonseroconversion after SARS-CoV-2 Infection","volume":"27","author":"W Liu","year":"2021","journal-title":"Emerg Infect Dis"},{"issue":"4","key":"pmed.1004157.ref043","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.cell.2020.06.043","article-title":"Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus","volume":"182","author":"B Korber","year":"2020","journal-title":"Cell"},{"issue":"16","key":"pmed.1004157.ref044","doi-asserted-by":"crossref","first-page":"4220","DOI":"10.1016\/j.cell.2021.06.020","article-title":"Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum","volume":"184","author":"C Liu","year":"2021","journal-title":"Cell"},{"issue":"6556","key":"pmed.1004157.ref045","doi-asserted-by":"crossref","DOI":"10.1126\/science.abh1766","article-title":"Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants","volume":"373","author":"L Wang","year":"2021","journal-title":"Science"},{"issue":"11","key":"pmed.1004157.ref046","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20201181","article-title":"Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses","volume":"217","author":"F Schmidt","year":"2020","journal-title":"J Exp Med"},{"key":"pmed.1004157.ref047","doi-asserted-by":"crossref","first-page":"gzab033","DOI":"10.1093\/protein\/gzab033","article-title":"Comprehensive mapping of SARS-CoV-2 peptide epitopes for development of a highly sensitive serological test for total and neutralizing antibodies","volume":"35","author":"G Kumar","year":"2022","journal-title":"Protein Eng Des 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