ABSTRACT
In spite of the successful development of effective countermeasures against Covid-19, variants have and will continue to emerge that could compromise the efficacy of currently approved neutralizing antibodies and vaccines. Consequently, novel and more efficacious agents are urgently needed. We have developed a bispecific antibody, 2022, consisting of two antibodies, 2F8 and VHH18. 2F8 was isolated from our proprietary fully synthetic human IDEAL (Intelligently Designed and Engineered Antibody Library)-VH/VL library and VHH18 is a single domain antibody isolated from IDEAL-nanobody library. 2022 was constructed by attaching VHH18 to the C-terminal of Fc of 2F8. 2022 binds two non-overlapping epitopes simultaneously on the RBD of the SARS-CoV-2 spike protein and blocks the binding of RBD to human angiotensin-converting enzyme 2 (ACE2). 2022 potently neutralizes SARS-CoV-2 and all of the variants tested in both pseudovirus and live virus assays, including variants carrying mutations known to resist neutralizing antibodies approved under EUA and that reduce the protection efficiency of current effective vaccines. The half-maximum inhibitory concentration (IC50) of 2022 is 270 pM, 30 pM, 20 pM, and 1 pM, for wild-type, alpha, beta, and delta pseudovirus, respectively. In the live virus assay, 2022 has an IC50 of 26.4 pM, 13.3 pM, and 88.6 pM, for wild-type, beta, and delta live virus, respectively. In a mouse model of SARS-CoV-2, 2022 showed strong prophylactic and therapeutic effects. A single administration of 2022 intranasal (i.n.) or intraperitoneal (i.p.) 24 hours before virus challenge completely protected all mice from bodyweight loss, as compared with up to 20% loss of bodyweight in placebo treated mice. In addition, the lung viral titers were undetectable (FRNT assay) in all mice treated with 2022 either prophylactically or therapeutically, as compared with around 1x105 pfu/g lung tissue in placebo treated mice. In summary, bispecific antibody 2022 showed potent binding and neutralizing activity across a variety of SARS-CoV-2 variants and could be an attractive weapon to combat the ongoing waves of the COVID-19 pandemic propagated mainly by variants, especially, the much more contagious delta variant.
ABSTRACT
Objective To study the constituents in Melicope pteleifolia. Methods Plant material was isolated with 80% EtOH. Compounds were separated with chromatographic methods and their structures were elucidated on the basis of spectral analysis (EI-MS, 1H-NMR, and 13C-NMR) and chemical evidence. Results Five compounds were isolated from petrol ether or ethyl acetate soluble fraction. Their structures were identified as 3,5,3'-trihydroxy-4'-methoxy-7-(3-methylbut-2-enyloxy) flavone (pteleifolosin C, 1), 3,7-dimethoxyl kaempferol (kamatakenin, 2), vanillic acid (3), tricosanoic acid tetradecyl ester (4), and p-sitosterol (5), respectively. Conclusion Compound 1 is a new structure named pteleifolosin C. Compounds 2-4 are isolated from this plant for the first time.
ABSTRACT
AimTo explore the kinetic change of the IgG,T-cell subsets and IL-2 level from the mice infected with T. Spiralis. Methods The level of specific IgG A band IL-2 was determined by ELISA,the percentage of CD4+and CD8+ T-cells were examined by flow cytometry on 7, 14,21,28,35 days after mice infected with T. spiralis respectively. ResultAfter infected with T. spiralis,the level of IgG in mice rised gradually,and reached its peak on the 35th day. The change of T-cell subsets showed that CD4+T cells decreased,which CD8+Tcells increased. The ration of CD4+/CD8+cells decreased,and which was the obvious on the 14thday. It did not recover to normal level even on the 35th day. The IL-2 of level reached the peak on the 7th day after infected,then IL-2 level decreased quickly and lower than that of normal mice on 35th day after infected. Conclusion When the acute phase of T. spiralis infection,the immune function of host was inhibited. The protective immunity of against T. spiralis infection was cellular immunity mainly ,in cooperation with humoral immunity.
ABSTRACT
Objective To study the immune response induced by the mice immunized with Trichinella spiralis(T.spiralis) adult worm soluble antigen(AWSAg). Methods T.spiralis AWSAg was prepared to immunize Kunming strain mice. Dynamic changes of IgG, IL 2 and T lymphocyte subsets from immunized mice were determined after challenge infection on d 7, d 14 , d 21 , d 28 and d 35 . Results On d 7 after challenge infection, IgG and CD4 + T cells of immunized group were markedly elevated and persisted higher over the observation period. In contrast, CD4 + T cells and CD4/CD8 ratio were significantly decreased in unimmunized group resulted from immune suppression after infection. IL 2 levels reached the peak on d 7 and persisted in high level from d 7-d 21 in both immunized and unimmunized group after infection, then decreased gradually. Till 35 days after infection, IL 2 level was still higher than the normal mice. Conclusion Mice immunized with AWSAg of T. spiralis produced a potential cellular and humoral immune response.
ABSTRACT
Objective To study the chemical constituents of Evodia lepta.Methods The chemical constituents were isolated by chromatographic methods and their structures were elucidated by physicochemical characteristics and spectral data.Results Two compounds were isolated and their structures were identified as erythro-3-(1',2',3'-trihydroxy) isopentyl-7-hydroxycoumarin(Ⅰ) and?-daucosterol (Ⅱ).Conclusion CompoundⅠis a new one named evodosin A while compoundⅡis isolated from E. lepta for the first time.
