Author: 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.

VaccinesQ3 · MEDICINE

VSV-Based Vaccines Reduce Virus Shedding and Viral Load in Hamsters Infected with SARS-CoV-2 Variants of Concern

Q3 · MEDICINE

ArticleOA

Author: Gourdine, Tylisha ; Furuyama, Wakako ; Fletcher, Paige ; O'Donnell, Kyle L ; Shifflett, Kyle ; Marzi, Andrea ; Clancy, Chad S

The continued progression of the COVID-19 pandemic can partly be attributed to the ability of SARS-CoV-2 to mutate and introduce new viral variants. Some of these variants with the potential to spread quickly and conquer the globe are termed variants of concern (VOC). The existing vaccines implemented on a global scale are based on the ancestral strain, which has resulted in increased numbers of breakthrough infections as these VOC have emerged. It is imperative to show protection against VOC infection with newly developed vaccines. Previously, we evaluated two vesicular stomatitis virus (VSV)-based vaccines expressing the SARS-CoV-2 spike protein alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV) and demonstrated their fast-acting potential. Here, we prolonged the time to challenge; we vaccinated hamsters intranasally (IN) or intramuscularly 28 days prior to infection with three SARS-CoV-2 VOC—the Alpha, Beta, and Delta variants. IN vaccination with either the VSV-SARS2 or VSV-SARS2-EBOV resulted in the highest protective efficacy as demonstrated by decreased virus shedding and lung viral load of vaccinated hamsters. Histopathologic analysis of the lungs revealed the least amount of lung damage in the IN-vaccinated animals regardless of the challenge virus. This data demonstrates the ability of a VSV-based vaccine to not only protect from disease caused by SARS-CoV-2 VOC but also reduce viral shedding.

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Indication	Highest Phase	Country/Location	Organization	Date
Coronavirus Infections	Preclinical	-	Vyriad, Inc.Startup	10 Jan 2022

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