ABSTRACT
SARS-CoV-2 causing the worldwide pandemic has changed people's life in multiple aspects dramatically since it's first identified in Wuhan, China at the end of 2019. While the numbers of infected patients and death toll keep vigorous increasing, curbing the progression of the pandemic is an urgent goal. Efforts have been made to search for prophylactic and therapeutic approaches including neutralizing antibodies development. By reviewing dozens of studies on anti-spike antibodies identification, we concluded that (1) promising therapeutic antibodies are being fished out by various approaches, such as screening of single B cells of convalescent patients, recombinant antibody library and B cells of immunized animals; (2) the epitopes are mainly RBD, but also some non-RBD domains, without the requisite of overlapping with ACE2 binding sites; (3) Neutralizing antibodies are convergent to a few germline genes, including IGHV3-30, IGHV3-53, IGHV3-66, with varying levels of somatic mutations. This review summarizes the progress in neutralizing antibodies development and the germline enrichment of effective antibodies, which will shed light on COVID-19 treatment and vaccine design.
ABSTRACT
Combinatorial antibody libraries not only effectively reduce antibody discovery to a numbers game, but enable documentation of the history of antibody responses in an individual. The SARS-CoV-2 pandemic has prompted a wider application of this technology to meet the public health challenge of pandemic threats in the modern era. Herein, we used a combinatorial human antibody library constructed 20 years before the COVID-19 pandemic to discover three highly potent antibodies that selectively bind SARS-CoV-2 spike protein and neutralize authentic SARS-CoV-2 virus. Compared to neutralizing antibodies from COVID-19 patients with generally low somatic hypermutation (SHM), these antibodies contain over 13-22 SHMs, many of which are involved in specific interactions in crystal structures with SARS-CoV-2 spike RBD. The identification of these somatically mutated antibodies in a pre-pandemic library raises intriguing questions about the origin and evolution of human immune responses to SARS-CoV-2.
ABSTRACT
Objective To investigate the effect of vitamin D on platelet reactivity after combined treatment with aspirin and clopidogrel in elderly patients with ischemic stroke??Methods A total of 190 elderly patients with ischemic stroke treated with aspirin and clopidogrel in Beijing Bo′ai Hospital from June 2017 to August 2018 were enrolled in this study??Venous blood was collected for platelet aggregation rate,25?hydroxyvitamin D[25(OH)D] and clinical biochemical indexes during 1～2 weeks??According to 25 (OH) D quartile,the patients were further divided into Q1(≤7??18 μg／L) group ( n＝50),Q2: (＞7??18－≤9??39 μg／L) group (n＝50),Q3: (＞9??39－≤13??74 μg／L) group (50),Q4: (＞13??74 μg／L) (n＝40)??In order to evaluate the effect of calcitriol on platelet aggregation,platelet rich plasma ( PRP) in healthy group (15 cases) and clopidogrel resistance group (15 cases) were treated with calcitriol (10 nmol／L) and saline (37℃ pretreatment for 5 minutes),respectively,and to compare the difference of maximum platelet aggregation rate induced by ADP between the two treatments??Results There were significant differences in ADP? induced maximum platelet aggregation rate ( MPAR) (( 49??36 ± 23??34)%,( 48??80 ± 20??90)%, ( 37??02 ±18??24)%,(36??02± 14??46)%, F＝ 3??426, P＝ 0??018) and clopidogrel resistance ( CR)／ clopidogrel sensitive (CS) ratio (30／20,24／26,15／35,10／30,χ2＝15??119,P＝0??002) among the vitamin D quartiles (increasing)??Moreover, the MPAR and CR showed a decreasing trend with the increase of vitamin D concentration??Logistic regression analysis showed that serum 25( OH) D level was an independent inhibited factor for clopidogrel resistance in elderly patients with ischemic stroke ( Q4 vs Q1, OR＝0??699,95%CI 0??582～0??838,P＜0??001; Q3 vs Q1,OR＝0??848,95%CI 0??755－0??953,P＝0??006)??In vitro,compared with physiological saline,the aggregation rates of platelet in healthy group and CR group decreased after calcitriol pretreatment,and the difference was statistically significant ( healthy group: ( 69??8 ± 12??7 )% vs ( 58??6 ±11??5)%,t＝12??13,P＜0??001;CR group: ( 65??5 ± 8??3)% vs ( 56??3 ± 7??6)%, t＝11??48, P ＜0??001)??Conclusion Vitamin D reduces the high residual platelet reactivity after antiplatelet therapy??Further study is needed to determine whether vitamin D supplementation may improve the efficacy of clopidogrel??
