{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T10:03:27Z","timestamp":1768557807667,"version":"3.49.0"},"posted":{"date-parts":[[2022,9,21]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":52,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,9,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Patients with chronic lymphocytic leukemia (CLL) treated with B-cell pathway inhibitors and anti-CD20 antibodies exhibit low humoral response rate (RR) following SARS-CoV-2 vaccination. To investigate the relationship between the initial transcriptional response to vaccination with ensuing B and T cell immune responses, we performed a comprehensive immune transcriptome analysis flanked by antibody and T cell assays in peripheral blood prospectively collected from 15 CLL\/SLL patients vaccinated with heterologous BNT162b2\/ChAdOx1 with follow up at a single institution. The two-dose antibody RR was 40% increasing to 53% after booster. Patients on BTKi, venetoclax \u00b1 anti-CD20 antibody within 12 months of vaccination responded less well than those under BTKi alone. The two-dose T cell RR was 80% increasing to 93% after booster. Transcriptome studies revealed that seven patients showed interferon-mediated signaling activation within 2 days and one at 7 days after vaccination. Increasing counts of COVID-19 specific IGHV genes correlated with B-cell reconstitution and improved humoral RR. T cell responses in CLL patients appeared after vaccination regardless of treatment status. A higher humoral RR was associated with BTKi treatment and B-cell reconstitution. Boosting was particularly effective when intrinsic immune status was improved by CLL-treatment.<\/jats:p>","DOI":"10.1101\/2022.09.21.22280205","type":"posted-content","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T17:25:11Z","timestamp":1663781111000},"source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive analysis of immune responses in CLL patients after heterologous COVID-19 vaccination"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-5942","authenticated-orcid":false,"given":"Hye Kyung","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3526-9523","authenticated-orcid":false,"given":"Manuela A.","family":"Hoechstetter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maike","family":"Buchner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trang Thu","family":"Pham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Won","family":"Huh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2890-7515","authenticated-orcid":false,"given":"Katharina","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8721-9248","authenticated-orcid":false,"given":"Sabine","family":"Zange","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4373-0823","authenticated-orcid":false,"given":"Heiner von","family":"Buttlar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1370-4114","authenticated-orcid":false,"given":"Philipp","family":"Girl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8756-7821","authenticated-orcid":false,"given":"Roman","family":"W\u00f6lfel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Brandmeier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Pfeuffer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-0715","authenticated-orcid":false,"given":"Priscilla A.","family":"Furth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemens-Martin","family":"Wendtner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8319-9841","authenticated-orcid":false,"given":"Lothar","family":"Hennighausen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2022092309350534000_2022.09.21.22280205v1.1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006965"},{"key":"2022092309350534000_2022.09.21.22280205v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0959-x"},{"key":"2022092309350534000_2022.09.21.22280205v1.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011841"},{"issue":"1","key":"2022092309350534000_2022.09.21.22280205v1.4","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1111\/bjh.15146","article-title":"Humoral immune failure defined by immunoglobulin class and immunoglobulin G subclass deficiency is associated with shorter treatment-free and overall survival in Chronic Lymphocytic Leukaemia","volume":"181","year":"2018","journal-title":"Br J Haematol"},{"key":"2022092309350534000_2022.09.21.22280205v1.5","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.706285"},{"key":"2022092309350534000_2022.09.21.22280205v1.6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-567388"},{"issue":"3","key":"2022092309350534000_2022.09.21.22280205v1.7","first-page":"625","article-title":"Safety and efficacy of the BNT162b mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia","volume":"107","year":"2022","journal-title":"Haematologica"},{"issue":"2","key":"2022092309350534000_2022.09.21.22280205v1.8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1111\/ejh.13722","article-title":"Reasons and consequences of COVID-19 vaccine failure in patients with chronic lymphocytic leukemia","volume":"108","year":"2022","journal-title":"Eur J Haematol"},{"issue":"9","key":"2022092309350534000_2022.09.21.22280205v1.9","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1038\/s41375-021-01270-w","article-title":"COVID-19 vaccine efficacy in patients with chronic lymphocytic leukemia","volume":"35","year":"2021","journal-title":"Leukemia"},{"issue":"1","key":"2022092309350534000_2022.09.21.22280205v1.10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1182\/blood.2021013445","article-title":"Humoral and cellular responses after COVID-19 vaccination in anti-CD20-treated lymphoma patients","volume":"139","year":"2022","journal-title":"Blood"},{"key":"2022092309350534000_2022.09.21.22280205v1.11","doi-asserted-by":"crossref","unstructured":"Agha M , Blake M , Chilleo C , Wells A , Haidar G. Suboptimal response to COVID-19 mRNA vaccines in hematologic malignancies patients. medRxiv. 2021.","DOI":"10.1101\/2021.04.06.21254949"},{"key":"2022092309350534000_2022.09.21.22280205v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.06.008"},{"issue":"10","key":"2022092309350534000_2022.09.21.22280205v1.13","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1002\/ajh.26284","article-title":"BNT162b2 COVID-19 vaccine is significantly less effective in patients with hematologic malignancies","volume":"96","year":"2021","journal-title":"Am J Hematol"},{"key":"2022092309350534000_2022.09.21.22280205v1.14","doi-asserted-by":"publisher","DOI":"10.1182\/BLOOD.2021014085"},{"key":"2022092309350534000_2022.09.21.22280205v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-021-00528-x"},{"key":"2022092309350534000_2022.09.21.22280205v1.16","doi-asserted-by":"crossref","first-page":"104073","DOI":"10.1016\/j.ebiom.2022.104073","article-title":"Heterologous ChAdOx1\/BNT162b2 vaccination induces stronger immune response than homologous ChAdOx1 vaccination: The pragmatic, multi-center, three-arm, partially randomized HEVACC trial","volume":"80","year":"2022","journal-title":"EBioMedicine"},{"issue":"6","key":"2022092309350534000_2022.09.21.22280205v1.17","doi-asserted-by":"crossref","first-page":"104473","DOI":"10.1016\/j.isci.2022.104473","article-title":"Heterologous ChAdOx1-BNT162b2 vaccination in Korean cohort induces robust immune and antibody responses that includes Omicron","volume":"25","year":"2022","journal-title":"iScience"},{"key":"2022092309350534000_2022.09.21.22280205v1.18","unstructured":"European Medicines Agency (https:\/\/www.ema.europa.eu\/en\/news\/ema-ecdc-recommendations-heterologous-vaccination-courses-against-covid-19-mix-match-approach-can-be)"},{"key":"2022092309350534000_2022.09.21.22280205v1.19","doi-asserted-by":"crossref","unstructured":"Azzolini E , Pozzi C , Germagnoli L , et al. mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients. Life Sci Alliance. 2022;5(6).","DOI":"10.26508\/lsa.202201381"},{"key":"2022092309350534000_2022.09.21.22280205v1.20","doi-asserted-by":"crossref","unstructured":"Zaleska J , Kwasnik P , Paziewska M , et al. Response to anti-SARS-CoV-2 mRNA vaccines in multiple myeloma and chronic lymphocytic leukemia patients. Int J Cancer. 2022.","DOI":"10.1002\/ijc.34209"},{"key":"2022092309350534000_2022.09.21.22280205v1.21","first-page":"6831640","article-title":"Immunogenicity of Pfizer mRNA COVID-19 Vaccination Followed by J&J Adenovirus COVID-19 Vaccination in Two Patients with Chronic Lymphocytic Leukemia","volume":"2022","year":"2022","journal-title":"Case Rep Hematol"},{"issue":"6","key":"2022092309350534000_2022.09.21.22280205v1.22","doi-asserted-by":"crossref","first-page":"108728","DOI":"10.1016\/j.celrep.2021.108728","article-title":"Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients","volume":"34","year":"2021","journal-title":"Cell Rep"},{"issue":"3","key":"2022092309350534000_2022.09.21.22280205v1.23","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1111\/bjh.17877","article-title":"T-cell immune response after mRNA SARS-CoV-2 vaccines is frequently detected also in the absence of seroconversion in patients with lymphoid malignancies","volume":"196","year":"2022","journal-title":"Br J Haematol"},{"key":"2022092309350534000_2022.09.21.22280205v1.24","doi-asserted-by":"crossref","unstructured":"Le Bert N , Clapham HE , Tan AT , et al. Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection. J Exp Med. 2021;218(5).","DOI":"10.1084\/jem.20202617"},{"issue":"2","key":"2022092309350534000_2022.09.21.22280205v1.25","doi-asserted-by":"crossref","first-page":"110680","DOI":"10.1016\/j.celrep.2022.110680","article-title":"mRNA vaccination in octogenarians 15 and 20 months after recovery from COVID-19 elicits robust immune and antibody responses that include Omicron","volume":"39","year":"2022","journal-title":"Cell Rep"},{"issue":"4","key":"2022092309350534000_2022.09.21.22280205v1.26","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3390\/idr14040057","article-title":"Mix-and-Match COVID-19 Vaccinations (Heterologous Boost): A Review","volume":"14","year":"2022","journal-title":"Infect Dis Rep"},{"key":"2022092309350534000_2022.09.21.22280205v1.27","doi-asserted-by":"crossref","first-page":"101642","DOI":"10.1016\/j.eclinm.2022.101642","article-title":"Immune responses following 3rd and 4th doses of heterologous and homologous COVID-19 vaccines in kidney transplant recipients","volume":"53","year":"2022","journal-title":"EClinicalMedicine"},{"issue":"12","key":"2022092309350534000_2022.09.21.22280205v1.28","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.1515\/cclm-2020-1183","article-title":"Results of the first pilot external quality assessment (EQA) scheme for anti-SARS-CoV2-antibody testing","volume":"58","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"2022092309350534000_2022.09.21.22280205v1.29","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"2022092309350534000_2022.09.21.22280205v1.30","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts635"},{"key":"2022092309350534000_2022.09.21.22280205v1.31","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"2022092309350534000_2022.09.21.22280205v1.32","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2022092309350534000_2022.09.21.22280205v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2931"},{"key":"2022092309350534000_2022.09.21.22280205v1.34","doi-asserted-by":"crossref","unstructured":"Wickham H. Ggplot2 : elegant graphics for data analysis. New York: Springer; 2009.","DOI":"10.1007\/978-0-387-98141-3"},{"key":"2022092309350534000_2022.09.21.22280205v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364"},{"key":"2022092309350534000_2022.09.21.22280205v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3979"},{"key":"2022092309350534000_2022.09.21.22280205v1.37","first-page":"20406207221090150","article-title":"Safety and immunogenicity of the BNT162b2 mRNA Covid-19 vaccine in patients with chronic lymphocytic leukemia: a prospective study","volume":"13","year":"2022","journal-title":"Ther Adv Hematol"},{"issue":"2","key":"2022092309350534000_2022.09.21.22280205v1.38","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/s41375-021-01424-w","article-title":"Covid-19 in patients with chronic lymphocytic leukemia: clinical outcome and B- and T-cell immunity during 13 months in consecutive patients","volume":"36","year":"2022","journal-title":"Leukemia"},{"issue":"2","key":"2022092309350534000_2022.09.21.22280205v1.39","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.humimm.2021.10.007","article-title":"Landscapes and dynamic diversifications of B-cell receptor repertoires in COVID-19 patients","volume":"83","year":"2022","journal-title":"Hum Immunol"},{"issue":"7889","key":"2022092309350534000_2022.09.21.22280205v1.40","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/s41586-021-04117-7","article-title":"Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants","volume":"600","year":"2021","journal-title":"Nature"},{"key":"2022092309350534000_2022.09.21.22280205v1.41","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41421-020-0168-9","article-title":"Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing","volume":"6","year":"2020","journal-title":"Cell Discov"},{"issue":"1","key":"2022092309350534000_2022.09.21.22280205v1.42","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/s41392-021-00610-7","article-title":"Rapid isolation and immune profiling of SARS-CoV-2 specific memory B cell in convalescent COVID-19 patients via LIBRA-seq","volume":"6","year":"2021","journal-title":"Signal Transduct Target Ther"},{"issue":"9","key":"2022092309350534000_2022.09.21.22280205v1.43","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1038\/s41590-020-0762-x","article-title":"Single-cell landscape of immunological responses in patients with COVID-19","volume":"21","year":"2020","journal-title":"Nat Immunol"},{"issue":"1","key":"2022092309350534000_2022.09.21.22280205v1.44","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/s41421-021-00321-x","article-title":"Dynamics of TCR repertoire and T cell function in COVID-19 convalescent individuals","volume":"7","year":"2021","journal-title":"Cell Discov"},{"issue":"1","key":"2022092309350534000_2022.09.21.22280205v1.45","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41392-021-00526-2","article-title":"Dynamic blood single-cell immune responses in patients with COVID-19","volume":"6","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"2022092309350534000_2022.09.21.22280205v1.46","doi-asserted-by":"crossref","unstructured":"Knabl L , Lee HK , Wieser M , et al. BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant. Commun Med (Lond). 2022;2(1).","DOI":"10.1038\/s43856-022-00083-x"},{"issue":"4","key":"2022092309350534000_2022.09.21.22280205v1.47","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1182\/bloodadvances.2021006633","article-title":"Cellular and humoral immune response to mRNA COVID-19 vaccination in subjects with chronic lymphocytic leukemia","volume":"6","year":"2022","journal-title":"Blood Adv"},{"issue":"1","key":"2022092309350534000_2022.09.21.22280205v1.48","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/s41467-022-28578-0","article-title":"Humoral and cellular responses after a third dose of SARS-CoV-2 BNT162b2 vaccine in patients with lymphoid malignancies","volume":"13","year":"2022","journal-title":"Nat Commun"},{"issue":"6","key":"2022092309350534000_2022.09.21.22280205v1.49","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/bjh.18149","article-title":"Rituximab-treated patients with lymphoma develop strong CD8 T-cell responses following COVID-19 vaccination","volume":"197","year":"2022","journal-title":"Br J Haematol"},{"issue":"4","key":"2022092309350534000_2022.09.21.22280205v1.50","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","year":"2022","journal-title":"Haematologica"},{"issue":"23","key":"2022092309350534000_2022.09.21.22280205v1.51","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","year":"2021","journal-title":"Blood"},{"key":"2022092309350534000_2022.09.21.22280205v1.52","doi-asserted-by":"crossref","first-page":"686768","DOI":"10.3389\/fimmu.2021.686768","article-title":"BTK Inhibitors in Chronic Lymphocytic Leukemia: Biological Activity and Immune Effects","volume":"12","year":"2021","journal-title":"Front Immunol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2022.09.21.22280205","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:50:52Z","timestamp":1768488652000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2022.09.21.22280205"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":52,"URL":"https:\/\/doi.org\/10.1101\/2022.09.21.22280205","relation":{},"subject":[],"published":{"date-parts":[[2022,9,21]]},"subtype":"preprint"}}