scholarly journals Neutralization of SARS-CoV-2 variants by rVSV-ΔG-spike-elicited human sera

2021 ◽  
Author(s):  
Yfat Yahalom-Ronen ◽  
Noam Erez ◽  
Morly Fisher ◽  
Hadas Tamir ◽  
Boaz Politi ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Vaccine Candidate ◽  
Neutralization Capacity ◽  
Human Sera ◽  
Vesicular Stomatitis ◽  
Alpha Beta

BriLife® (rVSV- ΔG-spike) is a SARS-CoV-2 vaccine candidate based on vesicular stomatitis virus (VSV) platform. We show that sera from BriLife® vaccinees maintain neutralization capacity against alpha, beta, gamma and delta SARS-CoV-2 variants. BriLife® spontaneously-acquired spike mutations, corresponding with key SARS-CoV-2 variants mutations, may contribute to its efficacy against SARS-CoV-2 variants.

scholarly journals A methyltransferase-defective VSV-based SARS-CoV-2 vaccine candidate provides complete protection against SARS-CoV-2 infection in hamsters

2021 ◽  
Author(s):  
Mijia Lu ◽  
Yuexiu Zhang ◽  
Piyush Dravid ◽  
Anzhong Li ◽  
Cong Zeng ◽  
...  
Keyword(s):  
Cell Culture ◽  
Immune Responses ◽  
Vesicular Stomatitis Virus ◽  
Vaccine Candidate ◽  
Viral Mrna ◽  
S Protein ◽  
Vaccine Candidates ◽  
Syrian Golden Hamsters ◽  
Vesicular Stomatitis ◽  
Immunocompromised Mice

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to dramatic economic and health burdens. Although the worldwide SARS-CoV-2 vaccination campaign has begun, exploration of other vaccine candidates is needed due to the uncertainties of the current approved vaccines such as durability of protection, cross-protection against variant strains, and costs of long-term production, and storage. In this study, we developed a methyltransferase-defective recombinant vesicular stomatitis virus (mtdVSV)-based SARS-CoV-2 vaccine candidate. We generated mtdVSVs expressing SARS-CoV-2 full-length spike (S), S1, or its receptor binding domain (RBD). All these recombinant viruses grew to high titers in mammalian cells despite high attenuation in cell culture. SARS-CoV-2 S protein and its truncations were highly expressed by the mtdVSV vector. These mtdVSV-based vaccine candidates were completely attenuated in both immunocompetent and immunocompromised mice. Among these constructs, mtdVSV-S induced high levels of SARS-CoV-2 specific neutralizing antibodies (NAbs) and Th1-biased T cell immune responses in mice. Syrian golden hamsters immunized with mtdVSV-S triggered SARS-CoV-2 specific NAbs that were higher than convalescent plasma from convalescent COVID-19 patients. In addition, hamsters immunized with mtdVSV-S were completely protected against SARS-CoV-2 replication in lung and nasal turbinate tissues, cytokine storm, and lung pathology. Collectively, our data demonstrate that mtdVSV expressing SARS-CoV-2 S protein is a safe and highly efficacious vaccine candidate against SARS-CoV-2 infection. Significance Viral mRNA cap methyltransferase (MTase) is essential for mRNA stability, protein translation, and innate immune evasion. Thus, viral mRNA cap MTase activity is a novel target for development of live attenuated or live vectored vaccine candidates. Here, we developed a panel of MTase-defective recombinant recombinant vesicular stomatitis virus (mtdVSV)-based SARS-CoV-2 vaccine candidates expressing full-length S, S1, or several versions of the RBD. These mtdVSV-based vaccine candidates grew to high titers in cell culture and were completely attenuated in both immunocompetent and immunocompromised mice. Among these vaccine candidates, mtdVSV-S induces high levels of SARS-CoV-2 specific neutralizing antibody (Nabs) and Th1-biased immune responses in mice. Syrian golden hamsters immunized with mtdVSV-S triggered SARS-CoV-2 specific NAbs that were higher than convalescent plasma from COVID-19 recovered patients. Furthermore, hamsters immunized with mtdVSV-S were completely protected against SARS-CoV-2 challenge. Thus, mtdVSV is a safe and highly effective vector to deliver SARS-CoV-2 vaccine.

scholarly journals Recombinant vesicular stomatitis virus-based dengue-2 vaccine candidate induces humoral response and protects mice against lethal infection

2016 ◽  
Vol 12 (9) ◽  
pp. 2327-2333 ◽  
Author(s):  
Flavio Lauretti ◽  
Anasuya Chattopadhyay ◽  
Rafael Freitas de Oliveira França ◽  
Luiza Castro-Jorge ◽  
John Rose ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Vaccine Candidate ◽  
Humoral Response ◽  
Lethal Infection ◽  
Vesicular Stomatitis

scholarly journals A Viable Recombinant Rhabdovirus Lacking Its Glycoprotein Gene and Expressing Influenza Virus Hemagglutinin and Neuraminidase Is a Potent Influenza Vaccine

2014 ◽  
Vol 89 (5) ◽  
pp. 2820-2830 ◽  
Author(s):  
Alex B. Ryder ◽  
Linda Buonocore ◽  
Leatrice Vogel ◽  
Raffael Nachbagauer ◽  
Florian Krammer ◽  
...  
Keyword(s):  
Cell Culture ◽  
Influenza Virus ◽  
Influenza Vaccine ◽  
Vesicular Stomatitis Virus ◽  
Recombinant Virus ◽  
Vaccine Candidate ◽  
Influenza Vaccines ◽  
Glycoprotein Gene ◽  
Influenza Virus Hemagglutinin ◽  
Vesicular Stomatitis

ABSTRACTThe emergence of novel influenza viruses that cause devastating human disease is an ongoing threat and serves as an impetus for the continued development of novel approaches to influenza vaccines. Influenza vaccine development has traditionally focused on producing humoral and/or cell-mediated immunity, often against the viral surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). Here, we describe a new vaccine candidate that utilizes a replication-defective vesicular stomatitis virus (VSV) vector backbone that lacks the native G surface glycoprotein gene (VSVΔG). The expression of the H5 HA of an H5N1 highly pathogenic avian influenza virus (HPAIV), A/Vietnam/1203/04 (VN1203), and the NA of the mouse-adapted H1N1 influenza virus A/Puerto Rico/8/34 (PR8) in the VSVΔG vector restored the ability of the recombinant virus to replicate in cell culture, without the requirement for the addition of trypsin. We show here that this recombinant virus vaccine candidate was nonpathogenic in mice when given by either the intramuscular or intranasal route of immunization and that thein vivoreplication of VSVΔG-H5N1 is profoundly attenuated. This recombinant virus also provided protection against lethal H5N1 infection after a single dose. This novel approach to vaccination against HPAIVs may be widely applicable to other emerging strains of influenza virus.IMPORTANCEPreparation for a potentially catastrophic influenza pandemic requires novel influenza vaccines that are safe, can be produced and administered quickly, and are effective, both soon after administration and for a long duration. We have created a new influenza vaccine that utilizes an attenuated vesicular stomatitis virus (VSV) vector, to deliver and express influenza virus proteins against which vaccinated animals develop potent antibody responses. The influenza virus hemagglutinin and neuraminidase proteins, expressed on the surface of VSV particles, allowed this vaccine to grow in cell culture and induced a potent antibody response in mice that was effective against infection with a lethal influenza virus. The mice showed no adverse reactions to the vaccine, and they were protected against an otherwise lethal influenza infection after only 14 days postvaccination and after as many as 140 days postvaccination. The ability to rapidly produce this safe and effective vaccine in cell culture is additionally advantageous.

scholarly journals Recoding of the Vesicular Stomatitis Virus L Gene by Computer-Aided Design Provides a Live, Attenuated Vaccine Candidate

mBio ◽  
2015 ◽  
Vol 6 (2) ◽  
Author(s):  
Bingyin Wang ◽  
Chen Yang ◽  
Gergely Tekes ◽  
Steffen Mueller ◽  
Aniko Paul ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Large Scale ◽  
Vaccine Candidate ◽  
Rna Virus ◽  
Live Attenuated Vaccine ◽  
Live Attenuated Vaccines ◽  
Codon Pair Bias ◽  
Codon Pair ◽  
Vesicular Stomatitis ◽  
Codon Pairs

ABSTRACTCodon pair bias (CPB), which has been observed in all organisms, is a neglected genomic phenomenon that affects gene expression. CPB results from synonymous codons that are paired more or less frequently in ORFeomes regardless of codon bias. The effect of an individual codon pair change is usually small, but when it is amplified by large-scale genome recoding, strikingly altered biological phenotypes are observed. The utility of codon pair bias in the development of live attenuated vaccines was recently demonstrated by recodings of poliovirus (a positive-strand RNA virus) and influenza virus (a negative-strand segmented RNA virus). Here, the L gene of vesicular stomatitis virus (VSV), a nonsegmented negative-sense RNA virus, was partially recoded based on codon pair bias. Totals of 858 and 623 silent mutations were introduced into a 5′-terminal segment of the viral L gene (designated L1) to create sequences containing either overrepresented or underrepresented codon pairs, designated L1sdmaxand L1min, respectively. Analysis revealed that recombinant VSV containing the L1minsequence could not be recovered, whereas the virus with the sdmax sequence showed a modest level of attenuation in cell culture. More strikingly, in mice the L1sdmaxvirus was almost as immunogenic as the parental strain but highly attenuated. Taken together, these results open a new road to attain a balance between VSV virulence and immunogenicity, which could serve as an example for the attenuation of other negative-strand, nonsegmented RNA viruses.IMPORTANCEVesicular stomatitis virus (VSV) is the prototypic rhabdovirus in the orderMononegavirales. A wide range of human pathogens belong to this family. Using a unique computer algorithm and large-scale genome synthesis, we attempted to develop a live attenuated vaccine strain for VSV, which could be used as an antigen delivery platform for humans. Recombinant VSVs with distinct codon pair biases were rationally designed, constructed, and analyzed in both cell culture and an animal model. One such recombinant virus, L1sdmax, contained extra overrepresented codon pairs in its L gene open reading frame (ORF) and showed promise as an effective vaccine candidate because of a favorable balance between virulence and immunogenicity. Our study not only contributes to the understanding of the underlying mechanism of codon pair bias but also may facilitate the development of live attenuated vaccines for other viruses in the orderMononegavirales.

scholarly journals The Murine Double-Stranded RNA-Dependent Protein Kinase PKR Is Required for Resistance to Vesicular Stomatitis Virus

2000 ◽  
Vol 74 (20) ◽  
pp. 9580-9585 ◽  
Author(s):  
David F. Stojdl ◽  
Ninan Abraham ◽  
Shane Knowles ◽  
Ricardo Marius ◽  
Ann Brasey ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Vesicular Stomatitis Virus ◽  
Acute Infection ◽  
Encephalomyocarditis Virus ◽  
Wild Type ◽  
Dependent Protein Kinase ◽  
Double Stranded Rna ◽  
Dependent Protein ◽  
Vesicular Stomatitis ◽  
Alpha Beta

ABSTRACT Interferon (IFN)-induced antiviral responses are mediated through a variety of proteins, including the double-stranded RNA-dependent protein kinase PKR. Here we show that fibroblasts derived from PKR−/− mice are more permissive for vesicular stomatitis virus (VSV) infection than are wild-type fibroblasts and demonstrate a deficiency in alpha/beta-IFN-mediated protection. We further show that mice lacking PKR are extremely susceptible to intranasal VSV infection, succumbing within days after instillation with as few as 50 infectious viral particles. Again, alpha/beta-IFN was unable to rescue PKR−/− mice from VSV infection. Surprisingly, intranasally infected PKR−/− mice died not from pathology of the central nervous system but rather from acute infection of the respiratory tract, demonstrating high virus titers in the lungs compared to similarly infected wild-type animals. These results confirm the role of PKR as the major component of IFN-mediated resistance to VSV infection. Since previous reports have shown PKR to be nonessential for survival in animals challenged with encephalomyocarditis virus, influenza virus, and vaccinia virus (N. Abraham et al., J. Biol. Chem. 274:5953–5962, 1999; Y. Yang et al., EMBO J. 14:6095–6106, 1995), our findings serve to highlight the premise that host dependence on the various mediators of IFN-induced antiviral defenses is pathogen specific.

626: Initial Experience with Vesicular Stomatitis Virus as a Treatment for Bladder Cancer

2006 ◽  
Vol 175 (4S) ◽  
pp. 202-202
Author(s):  
Sherwin Zargaroff ◽  
Yuancheng Wang ◽  
Xiayong Zheng ◽  
Jian Pu ◽  
Savio L. Woo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Vesicular Stomatitis Virus ◽  
Initial Experience ◽  
Vesicular Stomatitis

Inhibition of Various Steps in the Replication Cycle of Vesicular Stomatitis Virus Contributes to Its Photoinactivation by AlPcS4 or Pc4 and Red Light

1999 ◽  
Vol 69 (3) ◽  
pp. 353 ◽  
Author(s):  
Anne C. E. Moor ◽  
Angeline E. Wagenaars-van Gompel ◽  
Ralph C. A. Hermanns ◽  
Jannes van der Meulen ◽  
Jolanda Smit ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Red Light ◽  
Replication Cycle ◽  
Vesicular Stomatitis
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