Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

硒螺旋藻对大鼠肝叶切除术后肝细胞再生和抗氧化能力的影响

目的研究硒螺旋藻（Se—SP）对大鼠肝叶切除术后肝细胞再生和抗氧化能力的影响，以印证其生物利用价值。方法用Wistar大鼠复制67％肝叶切除动物模型，设Se—SP高剂量（H）和低剂量（L）治疗组，术前以Se—SP灌胃7d；另设生理盐水（C）及假手术对照组（S）。于手术前及其后24h取鼠肝细胞，检测硒（Se）、丙二醛（MDA）含量及谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活性；利用免疫组化方法测定肝细胞增生核抗原（PCNA）表达指数，慧星实验检测过氧化氢诱导的肝细胞DNA损伤。结果与C，S组相比，H组、L组肝细胞中MDA水平明显降低（P〈0．05），而Se，GPx和SOD明显升高（P〈0．05）；肝细胞PCNA指数明显升高（P〈0．05），过氧化氢诱导的DNA损伤程度较轻。结论Se—SP对肝切除鼠肝细胞具有一定的抗氧化和促再生作用。     

正常人颈段脊柱结构内CGRP和SP阳性神经纤维的分布

目的 为深入探讨颈肩痛的发病机理。方法 用免疫组织化学方法观察人颈段脊柱结构内CGRP和SP阳性神经末梢存在的情况。结果 人颈段脊柱结构的纤维层内均有CGRP和SP免疫反应阳性神经末梢存在，多数神经末梢独立行走，呈树枝状或念珠状，少量神经末梢交织网状。结论 CGRP和SP可能参与了人颈段脊柱结构的伤害性感觉信息的传递。当人颈段脊柱结构的神经末梢受刺激时，可能引起CGRP和SP的释放和传递，这可能是引起原发性颈肩痛的原因之一。     

亮氨酸脑啡肽样和P物质样免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布

用PAP法研究亮氨酸脑啡肽样(L—ENK—LI)和P物质样(SP—LI)免疫反应物在大鼠延髓迷走神经背核簇和网状结构内的分布。证明在孤束核、迷走神经背核、外侧网状核外侧部及其外侧的区域内有大量的L-ENK样终末和纤维,在背侧和腹侧网状核之间的移行区内有中等量的分布,其余区内为少量。L-ENK样胞体在孤束核、咀侧腹外侧网状核、巨细胞网状核的腹侧部和α部、外侧旁巨细胞核以及中缝大核内均有许多分布,在迷走神经背核的尾侧部、背侧和腹侧网状核之间的移行区有中等量,其余区内为少量。SP样反应物的分布与L-ENK样物类似,但其终末和纤维的数量较L-ENK者略少,阳性胞体的数量除了在中缝核及外侧旁巨细胞核内侧端中的量较L-ENK样胞体多以外,在其余区内均较少。     

Localization of substance P- and enkephalin-like immunoreactivity in relation to catecholamine-containing cell bodies in the cat dorsolateral pontine tegmentum: an immunofluorescence study

The distribution of tyrosine hydroxylase-, substance P- and enkephalin-immunoreactive neurons in the cat dorsolateral pons was studied using the indirect immunofluorescence method of Coons. To allow for the visualization of substance P- and enkephalin-immunoreactive cell bodies, colchicine was injected either in the ventricular space or in the cerebral tissue. The distribution of the tyrosine hydroxylase-immunoreactive cell bodies corresponded with the well-known distribution of catecholamine cells in this area of the brain. The observation of adjacent sections treated separately with tyrosine hydroxylase- and enkephalin-antiserum revealed that most catecholaminergic cells contain enkephalin-immunoreactivity. In addition to this catecholamine-enkephalin cell population, a moderate number of substance P-immunoreactive cell bodies was found in dorsolateral pons. The peribrachial nuclei were found to be densely supplied with substance P- and enkephalin-immunoreactive fibers, whereas the medial subdivisions, which contain the majority of the catecholamine cells in the dorsolateral pons, display a moderate number of immunoreactive fibers. These results are suggestive of interactions between peptide-containing and catecholaminergic neurons and also between-peptide-containing and non-catecholamine-containing neurons in the cat dorsolateral pons.     

Localisation of CEA, β-HCG,SP1, and keratin in the tissue of lung carcinomas

Summary One hundred and twenty seven cases of lung tumors were studied by the immunoperoxidase technique for the presence of CEA and-HCG. Twenty-nine of these tumors were additionally stained for keratin and SP1. CEA and SP1 could be demonstrated in 80% of the studied cases, while-HCG was found in only 9%. SP1 revealed an almost identical staining pattern to CEA and keratin was found only in squamous cell carcinomas. The tissue positivity of none of these three markers correlated with tumor size, lymphnodal involvement or histological type.This study was supported by Deutsche Stiftung für Krebsforschung - Dr. Mildred Scheel-Stiftung     

Co-existence of glucagon- and substance P-like immunoreactivity in the chicken retina

This immunohistochemical study of chicken retina using flat-mounts shows that pancreatic glucagon- and substance P-like immunoreactive amacrine cells have more heterogeneous subpopulations than was previously understood to be the case. Using double-staining immunohistochemical procedures we demonstrate that a substantial proportion of all subtypes of glucagon-like immunoreactive cells contain substance P-like immunoreactivity and that the ratio of the amacrine cells containing both peptides to total immunoreactive cells varies according to position in the retinal and cell type. These results suggest that retinal cells may have different functions according to position or cell type.