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1.
J Allergy Clin Immunol ; 149(1): 77-78, 2022 01.
Article in English | MEDLINE | ID: covidwho-1665042
2.
Gastroenterology ; 162(2): 454-467, 2022 02.
Article in English | MEDLINE | ID: covidwho-1545689

ABSTRACT

BACKGROUND & AIM: Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was to assess serologic responses to messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared with healthy controls (HCs). METHODS: Prospective, controlled, multicenter Israeli study. Subjects enrolled received 2 BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibody levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinally. RESULTS: Overall, 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HCs. After the first vaccine dose, all HCs were seropositive, whereas ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose, all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (both P < .001). Neutralizing and inhibitory functions were both lower in anti-TNFα treated compared with non-anti-TNFα treated patients, and HCs (P < .03; P < .0001, respectively). Anti-TNFα drug levels and vaccine responses did not affect anti-spike levels. Infection rate (∼2%) and AEs were comparable in all groups. IBD activity was unaffected by BNT162b2. CONCLUSIONS: In this prospective study in patients with IBD stratified according to treatment, all patients mounted serologic response to 2 doses of BNT162b2; however, its magnitude was significantly lower in patients treated with anti-TNFα, regardless of administration timing and drug levels. Vaccine was safe. As vaccine serologic response longevity in this group may be limited, vaccine booster dose should be considered.


Subject(s)
/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/drug effects , Inflammatory Bowel Diseases/immunology , Tumor Necrosis Factor Inhibitors/immunology , Adult , Antibodies, Viral/blood , Antibodies, Viral/immunology , Case-Control Studies , Female , Humans , Inflammatory Bowel Diseases/drug therapy , Israel , Male , Middle Aged , Prospective Studies , SARS-CoV-2/immunology
3.
Immunol Cell Biol ; 99(8): 796-799, 2021 09.
Article in English | MEDLINE | ID: covidwho-1352474

ABSTRACT

The B-cell response to COVID-19 vaccines in convalescent individuals.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , B-Lymphocytes/immunology , COVID-19 Vaccines , Humans , Immunologic Memory , Walking
4.
J Allergy Clin Immunol ; 148(3): 739-749, 2021 09.
Article in English | MEDLINE | ID: covidwho-1253079

ABSTRACT

BACKGROUND: In mid-December 2020, Israel started a nationwide mass vaccination campaign against coronavirus disease 2019 (COVID-19). In the first few weeks, medical personnel, elderly citizens, and patients with chronic diseases were prioritized. As such, patients with primary and secondary immunodeficiencies were encouraged to receive the vaccine. Although the efficacy of RNA-based COVID-19 vaccines has been demonstrated in the general population, little is known about their efficacy and safety in patients with inborn errors of immunity (IEI). OBJECTIVE: Our aim was to evaluate the humoral and cellular immune response to COVID-19 vaccine in a cohort of patients with IEI. METHODS: A total of 26 adult patients were enrolled, and plasma and peripheral blood mononuclear cells were collected from them 2 weeks following the second dose of Pfizer-BioNTech COVID-19 vaccine. Humoral response was evaluated by testing anti-SARS-CoV-2 spike (S) receptor-binding domain and antinucleocapsid antibody titers and evaluating neutralizing ability by inhibition of receptor-binding domain-angiotensin-converting enzyme 2 binding. Cellular immune response was evaluated by using ELISpot, estimating IL-2 and IFN-γ secretion in response to pooled SARS-CoV-2 S- or M-peptides. RESULTS: Our cohort included 18 patients with a predominantly antibody deficiency, 2 with combined immunodeficiency, 3 with immune dysregulation, and 3 with other genetically defined diagnoses. Twenty-two of them were receiving immunoglobulin replacement therapy. Of the 26 patients, 18 developed specific antibody response, and 19 showed S-peptide-specific T-cell response. None of the patients reported significant adverse events. CONCLUSION: Vaccinating patients with IEI is safe, and most patients were able to develop vaccine-specific antibody response, S-protein-specific cellular response, or both.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine , Primary Immunodeficiency Diseases/complications , Adult , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/etiology , COVID-19/virology , Disease Susceptibility , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunity, Cellular , Male , Middle Aged , Primary Immunodeficiency Diseases/genetics , SARS-CoV-2/immunology , Young Adult
5.
Hum Vaccin Immunother ; 17(10): 3551-3553, 2021 10 03.
Article in English | MEDLINE | ID: covidwho-1242090

ABSTRACT

Neutralizing antibodies are the basis of almost all approved prophylactic vaccines and the foundation of effective protection from pathogens, including the recently emerging SARS Coronavirus 2 (SARS-CoV-2). However, the contribution of antibodies to protection and to the course of the disease during first-time exposure to a pathogen is unknown. We analyzed the antibodies and B cell responses in severe and mild COVID-19 patients. Despite our primary assumption that high antibody titers contribute to a mild disease, we found that severe COVID-19 illness, and not mild infection, correlates with strong anti-viral antibody and memory B cell responses. This phenomenon was also demonstrated for anti-Mycobacterium tuberculosis inhibiting antibodies that we recently isolated from an actively infected Tuberculosis-sick donor. This correlation between disease severity and antibody responses can be explained by the fact that high viral loads drive B cell stimulation and generation of high-affinity antibodies that will be protective upon future encounter with the particular pathogen.


Subject(s)
COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Antibody Formation , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
6.
PLoS Pathog ; 17(2): e1009165, 2021 02.
Article in English | MEDLINE | ID: covidwho-1079380

ABSTRACT

The interactions between antibodies, SARS-CoV-2 and immune cells contribute to the pathogenesis of COVID-19 and protective immunity. To understand the differences between antibody responses in mild versus severe cases of COVID-19, we analyzed the B cell responses in patients 1.5 months post SARS-CoV-2 infection. Severe, and not mild, infection correlated with high titers of IgG against Spike receptor binding domain (RBD) that were capable of ACE2:RBD inhibition. B cell receptor (BCR) sequencing revealed that VH3-53 was enriched during severe infection. Of the 22 antibodies cloned from two severe donors, six exhibited potent neutralization against authentic SARS-CoV-2, and inhibited syncytia formation. Using peptide libraries, competition ELISA and mutagenesis of RBD, we mapped the epitopes of the neutralizing antibodies (nAbs) to three different sites on the Spike. Finally, we used combinations of nAbs targeting different immune-sites to efficiently block SARS-CoV-2 infection. Analysis of 49 healthy BCR repertoires revealed that the nAbs germline VHJH precursors comprise up to 2.7% of all VHJHs. We demonstrate that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population. Moreover, our data support the use of combination antibody therapy to prevent and treat COVID-19.


Subject(s)
Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Convalescence , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Adult , Aged , Animals , Antibodies, Monoclonal/genetics , Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/genetics , Antibodies, Viral/immunology , COVID-19/genetics , COVID-19/immunology , Chlorocebus aethiops , Cloning, Molecular , Epitope Mapping , Epitopes/genetics , Epitopes/immunology , Female , Humans , Immunoglobulin G/genetics , Immunoglobulin G/immunology , Male , Middle Aged , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vero Cells
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