Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response ...is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment. The in vivo treatment efficiencies of three novel anti-EBOV mAbs at 12 h post-infection correlated with their in vitro anti-EBOV ADCC activities, without neutralizing activity. When they were treated with these mAbs, natural killer cell (NK)-deficient mice had lower viral clearance than WT mice, indicating that the anti-EBOV mechanism of the ADCC activity of these mAbs is predominantly mediated by NK cells. One potent anti-EBOV mAb (M318) displayed unprecedented neutralizing and ADCC activities (neutralization IC
, 0.018 μg/ml; ADCC EC
, 0.095 μg/ml). These results have important implications for the efficacy of antiviral drugs and vaccines as well as for pathogenicity studies of EBOV.
SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and ...immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (
= 5; 3:2), cohort 2 (
= 8; 6:2), cohort 3, or cohort 4 (both
= 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in
and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).
Nanoparticle Vaccines
In article number 2200443, Liangzhi Xie, Chengfeng Qin, and co‐workers develop a novel bivalent nanoparticle vaccine that confers protection against infection of multiple ...SARS‐CoV‐2 variants and Streptococcus pneumoniae. This universal polysaccharide–protein‐conjugated vaccine platform provides a powerful tool to fight against cocirculating viral and bacterial pathogens worldwide.
Purpose
Neutralizing antibodies, administrated through intravenous infusion, have shown to be highly efficacious in treating mild and moderate COVID-19 caused by SARS-CoV-2 infection in the lung. ...However, antibodies do not transport across the plasma-lung barrier efficiently, and up to 100 mg/kg dose was used in human causing significant supply and cost burdens. This study was to explore the feasibility of nebulized antibodies inhalation delivery as an alternative route.
Methods
HB27, a potent RBD-specific humanized monoclonal antibody (Zhu et al. in National Sci Rev. 8:nwaa297, 2020), showed excellent protection against SARS-CoV-2 in animal model and good safety profile in clinical studies. The pharmacokinetics and preliminary safety of HB27 administrated through the respiratory tract were studied in mice and cynomolgus monkeys here.
Results
At a single 5 mg/kg dose, the peak HB27 concentration in mice pulmonary epithelial lining fluid (ELF) reached 857.8 μg/mL, 670-fold higher than the PRNT
90
value of 1.28 μg/mL, and maintained above PRNT
90
over 240 h. In contrast, when administrated by intravenous injection at a 5 mg/kg dose, the antibody concentrations in mice ELF were below PRNT
90
value throughout, and were about 50-fold lower than that in the serum. In cynomolgus monkeys administrated with a single dose through inhalation, the antibody concentration in ELF remained high within 3 days. No drug-related safety concerns were observed in the studies.
Conclusions
The study demonstrated that nebulized neutralizing antibody delivery though inhalation could be a more efficient and efficacious alternative approach for treating COVID-19 and other respiratory infectious diseases, and warrants further evaluation in clinical studies.
SARS-CoV-2 variants have posed significant challenges to the hopes of using ancestral strain-based vaccines to address the risk of breakthrough infection by variants. We designed and developed a ...bivalent vaccine based on SARS-CoV-2 Alpha and Beta variants (named SCTV01C). SCTV01C antigens were stable at 25 oC for at least 6 months. In the presence of a squalene-based oil-in-water adjuvant SCT-VA02B, SCTV01C showed significant protection efficacy against antigen-matched Beta variant, with favorable safety profiles in rodents. Notably, SCTV01C exhibited cross-neutralization capacity against Omicron subvariants (BA.1, BA.1.1, BA.2, BA.3, and BA.4/5) in mice, superior to a WT (D614G)-based vaccine, which reinforced our previously published findings that SCTV01C exhibited broad-spectrum neutralizing potencies against over a dozen pre-Omicron variants and the Omicron BA.1 variant. In summary, variant-based multivalent protein vaccine could be a platform approach to address the challenging issues of emerging variants, vaccine hesitancy and the needs of affordable and thermal stable vaccines.
•SCTV01C antigens were stable at 25 oC for at least 6 months.•Potent efficacy of SCTV01C against antigen-matched SARS-CoV-2 variant strain.•Superior cross-neutralizing potency of SCTV01C against Omicron subvariants.•SCTV01C exhibited favorable safety profiles in preclinical safety studies.
Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are members of the Picornaviridae family and are considered the main causative agents of hand, foot and mouth disease (HFMD). In recent decades ...large HFMD outbreaks caused by EV71 and CVA16 have become significant public health concerns in the Asia-Pacific region. Vaccines and antiviral drugs are unavailable to prevent EV71 and CVA16 infection. In the current study, a chimeric antibody targeting a highly conserved peptide in the EV71 VP4 protein was isolated by using a phage display technique. The antibody showed cross-neutralizing capability against EV71 and CVA16 in vitro. The results suggest that this phage display-derived antibody will have great potential as a broad neutralizing antibody against EV71 and CVA16 after affinity maturation and humanization.
选择不同生态地区的代表性芸芥材料研究表明,我国芸芥形态特征差异明显,可分为全缘叶芸芥(如和田芸芥)与羽状裂叶芸芥2大类型。和田芸芥的植物学形态特征特殊,茎直立,茎杆光滑、无刺毛;基生叶和茎生叶均为完整叶,披针形,叶缘波状,叶脉脉序羽状,茎生叶略小,不抱茎,花蕾顶部光滑或被少量刺毛;花为乳黄色,花瓣上部开展,下部具长爪,具绿色脉纹;角果表面光滑,无毛,平生,紧贴于果轴,四棱状,先端具扁平的剑形喙;果梗粗,略长,种子卵形,灰色,千粒重3g左右。RAPD分子标记分析表明,和田芸芥与其他材料的遗传距离最大,具有其特征带,聚类分析中,独自成为一类。和田芸芥生育期与其他芸芥相近,无生殖隔离现象。由此推断,和田芸芥可能是我国芸芥种内的一个新类型,其分类地位有待进一步研究确定。
Twenty classic landraces of Yunjie(Eruca sativa Mill.) from 9 provinces and regions of China were selected based on the morphological characteristics. The Yunjie genetic resources can be divided into two types, i.e. entire leaf Yunjie and pinnatinnately parted leaf Yunjie. Hetian Yunjie is belonged to the former and the others to the latter. A dendrogram based on ten morphological characteristics showed that Hetian Yunjie was distinguished from other Yunjie in this study. Hetian Yunjie has hair-free stem, radical and stem with entire leaves with stipes and which are 9.0 cm long and 0.5 cm wide. Its netted venation on petals is green and its hair-free which is quardrangular in sec