A Phase 1, Double-blind, Randomized, Placebo-controlled, First-in-Human Study of the Safety and Immunogenicity of AdCOVID Administered as One or Two Doses

A study to evaluate the immune response and safety of AdCOVID administered as an intranasal spray in healthy adults.

开始日期2021-02-25

申办/合作机构

Altimmune, Inc.

100 项与 SARS-CoV-2 S protein x SARS-CoV S protein 相关的临床结果

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100 项与 SARS-CoV-2 S protein x SARS-CoV S protein 相关的转化医学

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0 项与 SARS-CoV-2 S protein x SARS-CoV S protein 相关的专利（医药）

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项与 SARS-CoV-2 S protein x SARS-CoV S protein 相关的文献（医药）

2021-02-01·European review for medical and pharmacological sciences

Evaluation of molecular interaction, physicochemical parameters and conserved pattern of SARS-CoV-2 Spike RBD and hACE2: in silico and molecular dynamics approach.

Article

作者: Lee, S-S ; Mallick, B ; Sharma, G ; Chakraborty, C ; Sharma, A R ; Bhattacharya, M

OBJECTIVERecent pandemic virus SARS-CoV-2 is a global warning for the healthcare system. The spike protein of virus SARS-CoV-2 is significant because of two reasons. Firstly, the spike protein of this virus binds with the human ACE2 (hACE2) receptor. Secondly, it has several antigenic regions that might be targeted for vaccine development. However, the structural analytical data for the spike protein of this virus is not available.MATERIALS AND METHODSHere, we performed an analysis to understand the structural two subunits of S glycoprotein (S gp) of SARS-CoV-2. Further, an analysis of secondary structure components and the tertiary structure analysis of RBD was carried out. We also performed molecular interaction analysis between S gp of this virus and hACE2 as well as between SARS-CoV S gp and hACE2 to compare the binding properties of these two viruses.RESULTSWe noted that the molecular interaction of SARS-CoV-2 S gp and hACE2 form eleven hydrogen bonds, while the molecular interaction of SARS-CoV S gp and hACE2 receptor form seven hydrogen bonds, indicating that the molecular interaction of SARS-CoV-2 S gp and hACE2 receptor is more stable than SARS-CoV S gp and hACE2 receptor. The pairwise sequence alignment of S gp SARS-CoV and SARS-CoV-2 shows several conserved residues of these two proteins. Besides, conserved pattern analysis of SARS-CoV-2 S gp and hACE2 revealed the presence of several highly conserved regions for these two proteins. The molecular dynamics simulation shows a stable interplay between SARS-CoV-2 S gp with the hACE2 receptor.CONCLUSIONSThe present study might help determine the SARS-CoV-2 virus entrance mechanism into the human cell. Moreover, the understanding of the conserved regions may help in the process of therapeutic development from the infection of the deadly virus.

2011-09-01·Vaccine3区 · 医学

Chimeric severe acute respiratory syndrome coronavirus (SARS-CoV) S glycoprotein and influenza matrix 1 efficiently form virus-like particles (VLPs) that protect mice against challenge with SARS-CoV

3区 · 医学

Article

作者: Ye V. Liu ; Margret Nathan ; Michael J. Massare ; Thomas Kort ; Gale Smith ; Lei Wang ; Dale L. Barnard

SARS-CoV was the cause of the global pandemic in 2003 that infected over 8000 people in 8 months. Vaccines against SARS are still not available. We developed a novel method to produce high levels of a recombinant SARS virus-like particles (VLPs) vaccine containing the SARS spike (S) protein and the influenza M1 protein using the baculovirus insect cell expression system. These chimeric SARS VLPs have a similar size and morphology to the wild type SARS-CoV. We tested the immunogenicity and protective efficacy of purified chimeric SARS VLPs and full length SARS S protein vaccines in a mouse lethal challenge model. The SARS VLP vaccine, containing 0.8 μg of SARS S protein, completely protected mice from death when administered intramuscular (IM) or intranasal (IN) routes in the absence of an adjuvant. Likewise, the SARS VLP vaccine, containing 4 μg of S protein without adjuvant, reduced lung virus titer to below detectable level, protected mice from weight loss, and elicited a high level of neutralizing antibodies against SARS-CoV. Sf9 cell-produced full length purified SARS S protein was also an effective vaccine against SARS-CoV but only when co-administered IM with aluminum hydroxide. SARS-CoV VLPs are highly immunogenic and induce neutralizing antibodies and provide protection against lethal challenge. Sf9 cell-based VLP vaccines are a potential tool to provide protection against novel pandemic agents.

Scientific Reports3区 · 综合性期刊

Blockade of SARS-CoV-2 spike protein-mediated cell–cell fusion using COVID-19 convalescent plasma

3区 · 综合性期刊

ArticleOA

作者: Yao, Zhi Q ; Nguyen, Lam N T ; Zhang, Jinyu ; Khanal, Sushant ; Zhao, Juan ; Thakuri, Bal Krishna Chand ; Schank, Madison ; El Gazzar, Mohamed ; Zhang, Yi ; Wu, Xiao Y ; Ning, Shunbin ; Moorman, Jonathan P ; Dang, Xindi ; Nguyen, Lam N ; Adkins, James L ; Cao, Dechao ; Lu, Zeyuan ; Wang, Ling

AbstractThe recent COVID-19 pandemic poses a serious threat to global public health, thus there is an urgent need to define the molecular mechanisms involved in SARS-CoV-2 spike (S) protein-mediated virus entry that is essential for preventing and/or treating this emerging infectious disease. In this study, we examined the blocking activity of human COVID-19 convalescent plasma by cell–cell fusion assays using SARS-CoV-2-S-transfected 293 T as effector cells and ACE2-expressing 293 T as target cells. We demonstrate that the SARS-CoV-2 S protein exhibits a very high capacity for membrane fusion and is efficient in mediating virus fusion and entry into target cells. Importantly, we find that COVID-19 convalescent plasma with high titers of IgG neutralizing antibodies can block cell–cell fusion and virus entry by interfering with the SARS-CoV-2-S/ACE2 or SARS-CoV-S/ACE2 interactions. These findings suggest that COVID-19 convalescent plasma may not only inhibit SARS-CoV-2-S but also cross-neutralize SARS-CoV-S-mediated membrane fusion and virus entry, supporting its potential as a preventive and/or therapeutic agent against SARS-CoV-2 as well as other SARS-CoV infections.