ABSTRACT
BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. To prevent the massive COVID-19 burden, several vaccination campaigns were initiated. We performed a single center observational trial to evaluate adaptive immunity in naive healthcare workers upon BNT162b2 vaccination. MethodsSerological analysis was performed through conventional immunoassays. Antibody functionality was analyzed via in vitro neutralization assays. Circulating receptor-binding domain (RBD) specific B cells were assessed via flowcytometry. The induction of SARS-CoV-2 specific T cells was investigated through interferon-{gamma} release assay combined with flowcytometric profiling of activated CD4 and CD8 T cells. ResultsThree months after vaccination, all but one of the subjects (N = 31) displayed vaccine-induced neutralizing antibodies. In 10 out of 31 subjects, circulating RBD specific B cells were found of which the rate showed moderate correlation to serological parameters. Specific interferon-{gamma} release was present in all subjects and correlated with the significant upregulation of CD69 on CD4+ and CD8+ T cells and CD40L on CD4+ T cells. Interestingly, no relation was found between B and T cell parameters. In addition, one symptomatic breakthrough infection with the SARS-CoV-2 alpha variant of concern was reported. ConclusionThree months post vaccination, both humoral and cellular immune responses are detectable in all but one participant. No correlation was found between the magnitude of both B and T cell responses.
ABSTRACT
SARS-CoV-2 B.1.1.529, designated omicron, was recently identified as a new variant of concern by WHO and is rapidly replacing SARS-CoV-2 delta as the most dominant variant in many countries. Unfortunately, because of the high number of mutations present in the spike of SARS-CoV-2 omicron, most monoclonal antibodies (mAbs) currently approved for treatment of COVID-19 lose their in vitro neutralizing activity against this variant. We recently described a panel of human anti-SARS-CoV-2 mAbs that potently neutralize SARS-CoV-2 Wuhan, D614G and variants alpha, beta, gamma and delta. In this work, we evaluated our mAb panel for potential in vitro activity against SARS-CoV-2 delta and omicron. Three mAbs from our panel retain neutralizing activity against both delta and omicron, with mAb 3B8 still resulting in complete neutralization at a concentration as low as 0.02 g/ml for both variants. Overall, our data indicate that mAb 3B8 may have the potential to become a game-changer in the fight against the continuously evolving SARS-CoV-2.
ABSTRACT
Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants can escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent COVID-19 patient, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 Wuhan, alpha, beta, gamma and delta infection in vitro. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 g/ml, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the antigen levels and activity of von Willebrand factor cleaving protease ADAMTS13 in thrombotic thrombocytopenic purpura (TTP) patients and carriers.</p><p><b>METHODS</b>28 samples from 13 TTP patients and 10 samples from the carriers were examined. The activity of ADAMTS13 was measured by residue collagen binding assay, and antigen by a newly developed sandwich ELISA.</p><p><b>RESULTS</b>The mean ADAMTS13 level in Chinese normal controls (CN) was (600.93 +/- 145.36) mU/ml (n = 26) comparable to the level (1000 mU/ml) in pooled normal Caucasian plasma, and the activity was (74.79 +/- 11.81)%. Both the antigen level and activity of ADAMTS13 in congenital TTP patients either before plasma exchange (pre-PE) or interval relapse were quite lower than those in normal control, but were increased after PE (post-PE). The antigen was (331.40 +/- 109.85) mU/ml (P < 0.01, n = 10), and activity was (66.79 +/- 12.82)% (P > 0.05). The ADAMTS13 levels pre-PE in idiopathic TTP was (98.7 +/- 82.08) mU/ml (n = 11, P < 0.01), and that post-PE was up to (449.4 +/- 232.33) mU/ml (P < 0.01, n = 10). The activity of ADAMTS13 in patients pre-PE and post-PE were (22.23 +/- 19.07)% (P < 0.01) and (60.92 +/- 22.33)% (P > 0.05) respectively. In a secondary TTP patient the ADAMTS13 antigen was much higher than that in CN, and the activity was 6.00%.</p><p><b>CONCLUSION</b>The antigen and activity of ADAMTS13 in most TTP patients pre-PE are deficient, and these two indices in most TTP patients are paralleled. The reason for ADAMTS13 deficiency is congenital shortage or clearance by immune system, but it is unknown that why in some patients the ADAMTS13 antigen is extremely high but its activity is quite low.</p>