Elevated CD21
CD21low B-cells
COVID-19
CVID
Pfizer-BioNTech BNT162b2 mRNA vaccine
SARS-CoV-2
Journal
Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
19
11
2021
accepted:
24
02
2022
pubmed:
16
3
2022
medline:
9
6
2022
entrez:
15
3
2022
Statut:
ppublish
Résumé
Limited data is available on the effect of COVID-19 vaccination in immunocompromised individuals. Here, we provide the results from vaccinating a single-center cohort of patients with common variable immunodeficiency (CVID). In a prospective, open-label clinical trial, 50 patients with CVID and 90 age-matched healthy controls (HC) were analyzed for SARS-CoV-2 spike antibody (Ab) production after one or two doses of the Pfizer-BioNTech BNT162b2 mRNA vaccine. Additionally, in selected patients, SARS-CoV-2 spike-specific T-cells were assessed. A potent vaccine-induced anti-spike-specific IgG Ab response was observed in all the HC. In contrast, only 68.3% of the CVID patients seroconverted, with median titers of specific Ab being 83-fold lower than in HC. In fact, only 4/46 patients (8.6%) of patients who were seronegative at baseline reached the threshold for an optimal response (250 U/mL). Using the EUROclass definition, patients with either a reduced proportion, but not absolute counts, of switched memory B-cells or having an increased frequency of CD21 CVID patients with low frequency of switched memory B-cells or an increased frequency of CD21
Identifiants
pubmed: 35290571
doi: 10.1007/s10875-022-01244-2
pii: 10.1007/s10875-022-01244-2
pmc: PMC8922070
doi:
Substances chimiques
Antibodies, Viral
0
COVID-19 Vaccines
0
Vaccines, Synthetic
0
mRNA Vaccines
0
BNT162 Vaccine
N38TVC63NU
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
716-727Informations de copyright
© 2022. The Author(s).
Références
International Union of Immunological Societies Expert Committee on Primary I, Notarangelo LD, Fischer A, Geha RS, Casanova JL, Chapel H, et al. Primary immunodeficiencies: 2009 update. J Allergy Clin Immunol. 2009;124(6):1161–1178.
Fernando SL, Jang HS, Li J. The immune dysregulation of common variable immunodeficiency disorders. Immunol Lett. 2021;230:21–6.
doi: 10.1016/j.imlet.2020.12.002
Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International Consensus Document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4(1):38–59.
doi: 10.1016/j.jaip.2015.07.025
Milito C, Soccodato V, Collalti G, Lanciarotta A, Bertozzi I, Rattazzi M, et al. Vaccination in PADs. Vaccines (Basel). 2021;9(6):626.
Dalakas MC, Bitzogli K, Alexopoulos H. Anti-SARS-CoV-2 antibodies within IVIg preparations: cross-reactivities with seasonal coronaviruses, natural autoimmunity, and therapeutic implications. Front Immunol. 2021;12:627285.
doi: 10.3389/fimmu.2021.627285
Karbiener M, Farcet MR, Schwaiger J, Powers N, Lenart J, Stewart JM, et al. Plasma from post-COVID-19 and COVID-19-vaccinated donors results in highly potent SARS-CoV-2 neutralization by intravenous immunoglobulins. J Infect Dis. 2021 Sep 20:jiab482.
Kubota-Koketsu R, Terada Y, Yunoki M, Sasaki T, Nakayama EE, Kamitani W, et al. Neutralizing and binding activities against SARS-CoV-1/2, MERS-CoV, and human coronaviruses 229E and OC43 by normal human intravenous immunoglobulin derived from healthy donors in Japan. Transfusion. 2021;61(2):356–60.
doi: 10.1111/trf.16161
Milito C, Soccodato V, Auria S, Pulvirenti F, Quinti I. COVID-19 in complex common variable immunodeficiency patients affected by lung diseases. Curr Opin Allergy Clin Immunol. 2021;21(6):535–44.
doi: 10.1097/ACI.0000000000000789
Drabe CH, Hansen AE, Rasmussen LD, Larsen OD, Moller A, Mogensen TH, et al. Low morbidity in Danish patients with common variable immunodeficiency disorder infected with severe acute respiratory syndrome coronavirus 2. Infect Dis (Lond). 2021;53(12):953–8.
doi: 10.1080/23744235.2021.1957144
Lindahl HS, CIE.; Bergman, P. COVID-19 in a patient with Good's syndrome and in 13 patients with common variable immunodeficiency. Clin Immunol Commun. 2021;1:20–24.
Bergman P, Blennow O, Hansson L, Mielke S, Nowak P, Chen P, et al. Safety and efficacy of the mRNA BNT162b2 vaccine against SARS-CoV-2 in five groups of immunocompromised patients and healthy controls in a prospective open-label clinical trial. EBioMedicine. 2021;74:103705.
Hagin D, Freund T, Navon M, Halperin T, Adir D, Marom R, et al. Immunogenicity of Pfizer-BioNTech COVID-19 vaccine in patients with inborn errors of immunity. J Allergy Clin Immunol . 2021 Sep;148(3):739-749.
Salinas AF, Mortari EP, Terreri S, Quintarelli C, Pulvirenti F, Di Cecca S, et al. SARS-CoV-2 vaccine induced atypical immune responses in antibody defects: everybody does their best. J Clin Immunol. 2021;41(8):1709–22.
doi: 10.1007/s10875-021-01133-0
Amodio D, Ruggiero A, Sgrulletti M, Pighi C, Cotugno N, Medri C, et al. Humoral and cellular response following vaccination with the BNT162b2 mRNA COVID-19 vaccine in patients affected by primary immunodeficiencies. Front Immunol. 2021;12:727850.
Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77–85.
doi: 10.1182/blood-2007-06-091744
Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nat Rev Immunol. 2012;12(3):191–200.
doi: 10.1038/nri3158
Warnatz K, Schlesier M. Flowcytometric phenotyping of common variable immunodeficiency. Cytometry B Clin Cytom. 2008;74(5):261–71.
doi: 10.1002/cyto.b.20432
Higgins V, Fabros A, Kulasingam V. Quantitative measurement of anti-SARS-CoV-2 antibodies: analytical and clinical evaluation. J Clin Microbiol. 2021;59(4):e03149-20.
doi: 10.1128/JCM.03149-20
Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of Two RNA-based covid-19 vaccine candidates. N Engl J Med. 2020;383(25):2439–50.
doi: 10.1056/NEJMoa2027906
Rakhmanov M, Keller B, Gutenberger S, Foerster C, Hoenig M, Driessen G, et al. Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells. Proc Natl Acad Sci U S A. 2009;106(32):13451–6.
doi: 10.1073/pnas.0901984106
Unger S, Seidl M, van Schouwenburg P, Rakhmanov M, Bulashevska A, Frede N, et al. The TH1 phenotype of follicular helper T cells indicates an IFN-gamma-associated immune dysregulation in patients with CD21low common variable immunodeficiency. J Allergy Clin Immunol. 2018;141(2):730–40.
doi: 10.1016/j.jaci.2017.04.041
Warnatz K, Denz A, Drager R, Braun M, Groth C, Wolff-Vorbeck G, et al. Severe deficiency of switched memory B cells (CD27(+)IgM(-)IgD(-)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99(5):1544–51.
doi: 10.1182/blood.V99.5.1544
Wiesik-Szewczyk E, Rutkowska E, Kwiecien I, Korzeniowska M, Soldacki D, Jahnz-Rozyk K. Patients With common variable immunodeficiency complicated by autoimmune phenomena have lymphopenia and reduced Treg, Th17, and NK cells. J Clin Med. 2021;10(15):3356.
doi: 10.3390/jcm10153356
Lau D, Lan LY, Andrews SF, Henry C, Rojas KT, Neu KE, et al. Low CD21 expression defines a population of recent germinal center graduates primed for plasma cell differentiation. Sci Immunol. 2017;2(7):eaai8153.
Johnson JL, Rosenthal RL, Knox JJ, Myles A, Naradikian MS, Madej J, et al. The transcription factor T-bet resolves memory B cell subsets with distinct tissue distributions and antibody specificities in mice and humans. Immunity. 2020;52(5):842–855 e6.
Keller B, Strohmeier V, Harder I, Unger S, Payne KJ, Andrieux G, et al. The expansion of human T-bet(high)CD21(low) B cells is T cell dependent. Sci Immunol. 2021;6(64):eabh0891.
Knox JJ, Buggert M, Kardava L, Seaton KE, Eller MA, Canaday DH, et al. T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response. JCI Insight. 2017;2(8):e92943.
Knox JJ, Kaplan DE, Betts MR. T-bet-expressing B cells during HIV and HCV infections. Cell Immunol. 2017;321:26–34.
doi: 10.1016/j.cellimm.2017.04.012
Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV, Wang X, et al. Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus. Immunity. 2018;49(4):725–739 e6.
Tipton CM, Fucile CF, Darce J, Chida A, Ichikawa T, Gregoretti I, et al. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat Immunol. 2015;16(7):755–65.
doi: 10.1038/ni.3175
Edwards ESJ, Bosco JJ, Aui PM, Stirling RG, Cameron PU, Chatelier J, et al. Predominantly antibody-deficient patients with Non-infectious complications have reduced naive B, Treg, Th17, and Tfh17 cells. Front Immunol. 2019;10:2593.
doi: 10.3389/fimmu.2019.02593
Reincke ME, Payne KJ, Harder I, Strohmeier V, Voll RE, Warnatz K, et al. The antigen presenting potential of CD21(low) B cells. Front Immunol. 2020;11:535784.
Turner JS, O’Halloran JA, Kalaidina E, Kim W, Schmitz AJ, Zhou JQ, et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature. 2021;596(7870):109–13.
doi: 10.1038/s41586-021-03738-2
Unger S, Seidl M, Schmitt-Graeff A, Bohm J, Schrenk K, Wehr C, et al. Ill-defined germinal centers and severely reduced plasma cells are histological hallmarks of lymphadenopathy in patients with common variable immunodeficiency. J Clin Immunol. 2014;34(6):615–26.
doi: 10.1007/s10875-014-0052-1
Del Pino-Molina L, Lopez-Granados E, Lecrevisse Q, Torres Canizales J, Perez-Andres M, Blanco E, et al. Dissection of the pre-germinal center B-cell maturation pathway in common variable immunodeficiency based on standardized flow cytometric EuroFlow tools. Front Immunol. 2020;11:603972.
Andrews SF, Chambers MJ, Schramm CA, Plyler J, Raab JE, Kanekiyo M, et al. Activation dynamics and immunoglobulin evolution of pre-existing and newly generated human memory B cell responses to influenza hemagglutinin. Immunity. 2019;51(2):398-410 e5.
Gardulf A, Abolhassani H, Gustafson R, Eriksson LE, Hammarstrom L. Predictive markers for humoral influenza vaccine response in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2018;142(6):1922–1931 e2.
Zumaquero E, Stone SL, Scharer CD, Jenks SA, Nellore A, Mousseau B, et al. IFNgamma induces epigenetic programming of human T-bet(hi) B cells and promotes TLR7/8 and IL-21 induced differentiation. Elife. 2019;8.
Asano T, Boisson B, Onodi F, Matuozzo D, Moncada-Velez M, Maglorius Renkilaraj MRL, et al. X-linked recessive TLR7 deficiency in ~1% of men under 60 years old with life-threatening COVID-19. Sci Immunol. 2021;6(62):eabl4348.
Freudenhammer M, Voll RE, Binder SC, Keller B, Warnatz K. Naive- and memory-like CD21(low) B cell subsets share core phenotypic and signaling characteristics in systemic autoimmune disorders. J Immunol. 2020;205(8):2016–25.
doi: 10.4049/jimmunol.2000343