作者: Mukhopadhyay, Tarit K ; Kinek, Keith ; Reiserova, Lucia ; Yuan, Maoli ; Li, Shui L ; Horton, Melanie ; Li, Fengsheng ; Wu, Guoxin ; Zhang, Lan ; Gupta, Swati B ; Heidecker, Gwen ; Feinberg, Mark B ; Welch, Lisa S ; Citron, Michael ; Luo, Bin ; Bett, Andrew J ; Hou, Fuxiang ; Wilson, Aaron ; Cooper, Christopher L ; Espeseth, Amy S ; Secore, Susan ; Choi, Yesle ; Morrow, Gavin ; Strable, Erica ; Sayeed, Eddy ; Richardson, Douglas D ; Rukhman, Mark ; Parks, Christopher L ; DeStefano, Joanne

BACKGROUNDTo investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a single vaccine dose, we developed a SARS-CoV-2 candidate vaccine using the live vesicular stomatitis virus (VSV) chimeric virus approach previously used to develop a licensed Ebola virus vaccine.METHODSWe generated a replication-competent chimeric VSV-SARS-CoV-2 vaccine candidate by replacing the VSV glycoprotein (G) gene with coding sequence for the SARS-CoV-2 Spike glycoprotein (S). Immunogenicity of the lead vaccine candidate (VSV∆G-SARS-CoV-2) was evaluated in cotton rats and golden Syrian hamsters, and protection from SARS-CoV-2 infection also was assessed in hamsters.FINDINGSVSV∆G-SARS-CoV-2 delivered with a single intramuscular (IM) injection was immunogenic in cotton rats and hamsters and protected hamsters from weight loss following SARS-CoV-2 challenge. When mucosal vaccination was evaluated, cotton rats did not respond to the vaccine, whereas mucosal administration of VSV∆G-SARS-CoV-2 was found to be more immunogenic than IM injection in hamsters and induced immunity that significantly reduced SARS-CoV-2 challenge virus loads in both lung and nasal tissues.INTERPRETATIONVSV∆G-SARS-CoV-2 delivered by IM injection or mucosal administration was immunogenic in golden Syrian hamsters, and both vaccination methods effectively protected the lung from SARS-CoV-2 infection. Hamsters vaccinated by mucosal application of VSV∆G-SARS-CoV-2 also developed immunity that controlled SARS-CoV-2 replication in nasal tissue.FUNDINGThe study was funded by Merck Sharp & Dohme, Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, and The International AIDS Vaccine Initiative, Inc. (IAVI), New York, USA. Parts of this research was supported by the Biomedical Advanced Research and Development Authority (BARDA) and the Defense Threat Reduction Agency (DTRA) of the US Department of Defense.

2022-04-01·Vaccine3区 · 医学

Boosting of SARS-CoV-2 immunity in nonhuman primates using an oral rhabdoviral vaccine

3区 · 医学

Article

作者: Muñoz-Alía, Miguel Á ; Tesfay, Mulu ; Lathrum, Chase ; Kyratsous, Christos A ; Zhang, Lianwen ; Carey, Timothy ; Lee, Rachael M ; Petro, Christopher D ; Vandergaast, Rianna ; Peng, Kah-Whye ; Narjari, Riya ; Reiter, Samantha ; Suksanpaisan, Lukkana ; Sakuma, Toshie ; Ziegler, Christopher ; Ramachandran, Sabarinathan ; Graham, Melanie L ; Balakrishnan, Baskar ; Haselton, Michelle ; Baum, Alina ; Gnanadurai, Clement ; Waniger, Scott ; Russell, Stephen J ; Lech, Patrycja ; Packiriswamy, Nandakumar ; Sevola, Kara ; Krotova, Karina ; Russell, Luke ; Recker, Jordan ; Janecek, Jody L

An orally active vaccine capable of boosting SARS-CoV-2 immune responses in previously infected or vaccinated individuals would help efforts to achieve and sustain herd immunity. Unlike mRNA-loaded lipid nanoparticles and recombinant replication-defective adenoviruses, replicating vesicular stomatitis viruses with SARS-CoV-2 spike glycoproteins (VSV-SARS2) were poorly immunogenic after intramuscular administration in clinical trials. Here, by G protein trans-complementation, we generated VSV-SARS2(+G) virions with expanded target cell tropism. Compared to parental VSV-SARS2, G-supplemented viruses were orally active in virus-naive and vaccine-primed cynomolgus macaques, powerfully boosting SARS-CoV-2 neutralizing antibody titers. Clinical testing of this oral VSV-SARS2(+G) vaccine is planned.

2021-10-01·Biotechnology and Bioengineering2区 · 工程技术

Novel method for quantifying cells on carriers and its demonstration during SARS‐2 vaccine development

2区 · 工程技术

Article

作者: Jayson, Avital ; Epstein, Eyal ; Girshengorn, Meni ; Rosen, Osnat ; Goldvaser, Michael ; Levin, Lilach ; Monash, Arik ; Natan, Niva

AbstractThe most effective way to prevent and control infectious disease outbreak is through vaccines. The increasing use of vaccines has elevated the need to establish new manufacturing strategies. One of the major approaches is cell‐based production, which creates a need for high cell density to enable higher cell production levels. This has led to development of the technology of cell carriers, including micro and macro cell carriers. To follow the production process, quantifying the number of cells on these carriers is required, as well as the tracking of their viability and proliferation. However, owing to various carriers' unique structures, tracking the cell's is challenging using current traditional assays that were originally developed for monolayers of adherent cells. The current “gold standard” method is counting cell nuclei, separating cells from the carrier, staining with crystal violet, and visually counting under a microscope. This method is tedious and counts both live and dead cells. A few other techniques were developed but were specific to the carrier type and involved specialized equipment. In this study, we describe a broadly ranging method for counting cells on carriers that was developed and employed as part of the development of severe acute respiratory syndrome coronavirus 2 vaccine. The method is based on the Alamar blue dye, a well‐known, common marker for cell activity, and was found to be successful in tracking cell adsorption, cell growth, and viability on carriers. No separation of the cells from the carriers is needed, nor is any specialized equipment; the method is simple and rapid and provides comprehensive details necessary for process control of viral vaccine production in cells. This method can be easily implemented in any of a number of cell‐based processes and other unique platforms for measuring the growth of encapsulated cells.

100 项与 COVID-2019 vaccine(Vyriad) 相关的药物交易

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