scholarly journals Safety, Immunogenicity and Efficacy of a Recombinant Vesicular Stomatitis Virus Vectored Vaccine Against Severe Fever with Thrombocytopenia Syndrome and Heartland Bandaviruses

2021 ◽  
Author(s):  
Phillip Hicks ◽  
Jonna B. Westover ◽  
Tomaz B Manzoni ◽  
Brianne Roper ◽  
Gabrielle L Rock ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Genetic Manipulation ◽  
Case Fatality ◽  
Vaccine Platform ◽  
Vesicular Stomatitis ◽  
Immunocompetent Mice ◽  
Vectored Vaccine ◽  
Severe Fever ◽  
Promising Vaccine Candidate

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 8,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation and promiscuity in incorporating foreign glycoproteins into its virions. In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity and efficacy in mice. We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of Ifnar-/- mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection against lethal SFTSV challenge. Additionally, passive transfer of sera from immunized IFNAR-/- mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects mice against challenge with the closely related Heartland virus despite low neutralizing titers to the virus. Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate.

scholarly journals A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19

2021 ◽  
Author(s):  
Delphine C. Malherbe ◽  
Drishya Kurup ◽  
Christoph Wirblich ◽  
Adam J. Ronk ◽  
Chad Mire ◽  
...  
Keyword(s):  
Animal Model ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Specific Binding ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Hamster Model ◽  
Rapid Control ◽  
Vesicular Stomatitis ◽  
Vectored Vaccine

SUMMARYThe development of effective countermeasures against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal model of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.

scholarly journals A single dose of replication-competent VSV-vectored vaccine expressing SARS-CoV-2 S1 protects against virus replication in a hamster model of severe COVID-19

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Delphine C. Malherbe ◽  
Drishya Kurup ◽  
Christoph Wirblich ◽  
Adam J. Ronk ◽  
Chad Mire ◽  
...  
Keyword(s):  
Weight Loss ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Specific Binding ◽  
Vaccine Dose ◽  
Spike Protein ◽  
Hamster Model ◽  
Rapid Control ◽  
Vesicular Stomatitis ◽  
Vectored Vaccine

AbstractThe development of effective countermeasures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent responsible for the COVID-19 pandemic, is a priority. We designed and produced ConVac, a replication-competent vesicular stomatitis virus (VSV) vaccine vector that expresses the S1 subunit of SARS-CoV-2 spike protein. We used golden Syrian hamsters as animal models of severe COVID-19 to test the efficacy of the ConVac vaccine. A single vaccine dose elicited high levels of SARS-CoV-2 specific binding and neutralizing antibodies; following intranasal challenge with SARS-CoV-2, animals were protected from weight loss and viral replication in the lungs. No enhanced pathology was observed in vaccinated animals upon challenge, but some inflammation was still detected. The data indicate rapid control of SARS-CoV-2 replication by the S1-based VSV-vectored SARS-CoV-2 ConVac vaccine.

scholarly journals First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090)

2015 ◽  
Vol 2 (3) ◽  
Author(s):  
Jonathan D. Fuchs ◽  
Ian Frank ◽  
Marnie L. Elizaga ◽  
Mary Allen ◽  
Nicole Frahm ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Specific Binding ◽  
Vaccine Platform ◽  
Serious Adverse Events ◽  
Immunodeficiency Virus ◽  
Vesicular Stomatitis ◽  
Hiv 1

Abstract Background.  We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods.  Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 103 to 3.4 × 107 particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results.  Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions.  An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases.

scholarly journals Comparison of Four SARS-CoV-2 Neutralization Assays

Vaccines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 13
Author(s):  
Lydia Riepler ◽  
Annika Rössler ◽  
Albert Falch ◽  
André Volland ◽  
Wegene Borena ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
The Other ◽  
In Vitro Assays ◽  
The Novel ◽  
Effective Protection ◽  
Vaccine Candidates ◽  
Vesicular Stomatitis ◽  
Novel Coronavirus

Neutralizing antibodies are a major correlate of protection for many viruses including the novel coronavirus SARS-CoV-2. Thus, vaccine candidates should potently induce neutralizing antibodies to render effective protection from infection. A variety of in vitro assays for the detection of SARS-CoV-2 neutralizing antibodies has been described. However, validation of the different assays against each other is important to allow comparison of different studies. Here, we compared four different SARS-CoV-2 neutralization assays using the same set of patient samples. Two assays used replication competent SARS-CoV-2, a focus forming assay and a TCID50-based assay, while the other two assays used replication defective lentiviral or vesicular stomatitis virus (VSV)-based particles pseudotyped with SARS-CoV-2 spike. All assays were robust and produced highly reproducible neutralization titers. Titers of neutralizing antibodies correlated well between the different assays and with the titers of SARS-CoV-2 S-protein binding antibodies detected in an ELISA. Our study showed that commonly used SARS-CoV-2 neutralization assays are robust and that results obtained with different assays are comparable.

scholarly journals Immunovirotherapy with vesicular stomatitis virus and PD-L1 blockade enhances therapeutic outcome in murine acute myeloid leukemia

Blood ◽  
2016 ◽  
Vol 127 (11) ◽  
pp. 1449-1458 ◽  
Author(s):  
Weiwei Shen ◽  
Mrinal M. Patnaik ◽  
Autumn Ruiz ◽  
Stephen J. Russell ◽  
Kah-Whye Peng
Keyword(s):  
Acute Myeloid Leukemia ◽  
Vesicular Stomatitis Virus ◽  
Myeloid Leukemia ◽  
Therapeutic Outcome ◽  
Key Points ◽  
Vesicular Stomatitis ◽  
Immunocompetent Mice ◽  
Acute Myeloid

Key Points IV therapy with oncolytic VSV-IFNβ-NIS virus extends survival of immunocompetent mice with AML. The therapeutic outcome of VSV-IFNβ-NIS–treated mice with AML is augmented by anti-PD-L1 immunotherapy.

scholarly journals Neutralizing activity of Sputnik V vaccine sera against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Satoshi Ikegame ◽  
Mohammed Siddiquey ◽  
Chuan-Tien Hung ◽  
Griffin Haas ◽  
Luca Brambilla ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Cell Line ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
The Novel ◽  
Serum Samples ◽  
Egfp Reporter ◽  
Vesicular Stomatitis ◽  
Reduced Activity

Abstract The novel pandemic betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected at least 120 million people since its identification as the cause of a December 2019 viral pneumonia outbreak in Wuhan, China1,2. Despite the unprecedented pace of vaccine development, with six vaccines already in use worldwide, the emergence of SARS-CoV-2 ‘variants of concern’ (VOC) across diverse geographic locales have prompted re-evaluation of strategies to achieve universal vaccination3. All three officially designated VOC carry Spike (S) polymorphisms thought to enable escape from neutralizing antibodies elicited during initial waves of the pandemic4–8. Here, we characterize the biological consequences of the ensemble of S mutations present in VOC lineages B.1.1.7 (501Y.V1) and B.1.351 (501Y.V2). Using a replication-competent EGFP-reporter vesicular stomatitis virus (VSV) system, rcVSV-CoV2-S, which encodes S from SARS coronavirus 2 in place of VSV-G, and coupled with a clonal HEK-293T ACE2 TMPRSS2 cell line optimized for highly efficient S-mediated infection, we determined that only 1 out of 12 serum samples from a cohort of recipients of the Gamaleya Sputnik V Ad26 / Ad5 vaccine showed effective neutralization (IC90) of rcVSV-CoV2-S: B.1.351 at full serum strength. The same set of sera efficiently neutralized S from B.1.1.7 and showed only moderately reduced activity against S carrying the E484K substitution alone. Taken together, our data suggest that control of some emergent SARS-CoV-2 variants may benefit from updated vaccines.

scholarly journals Rapid Quantification of SARS-CoV-2-Neutralizing Antibodies Using Propagation-Defective Vesicular Stomatitis Virus Pseudotypes

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 386 ◽  
Author(s):  
Ferdinand Zettl ◽  
Toni Luise Meister ◽  
Tanja Vollmer ◽  
Bastian Fischer ◽  
Jörg Steinmann ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Neutralization Test ◽  
Pearson Correlation ◽  
Spike Protein ◽  
Virus Neutralization ◽  
Pseudotype Virus ◽  
Vesicular Stomatitis ◽  
Level 1 ◽  
Biosafety Level

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2, a new member of the genus Betacoronavirus, is a pandemic virus, which has caused numerous fatalities, particularly in the elderly and persons with underlying morbidities. At present, there are no approved vaccines nor antiviral therapies available. The detection and quantification of SARS-CoV-2-neutralizing antibodies plays a crucial role in the assessment of the immune status of convalescent COVID-19 patients, evaluation of recombinant therapeutic antibodies, and the evaluation of novel vaccines. To detect SARS-CoV-2-neutralizing antibodies, classically, a virus-neutralization test has to be performed at biosafety level 3, considerably limiting the general use of this test. In the present work, a biosafety level 1 pseudotype virus assay based on a propagation-incompetent vesicular stomatitis virus (VSV) has been used to determine the neutralizing antibody titers in convalescent COVID-19 patients. The neutralization titers in serum of two independently analyzed patient cohorts were available within 18 h and correlated well with those obtained with a classical SARS-CoV-2 neutralization test (Pearson correlation coefficients of r = 0.929 and r = 0.939, respectively). Most convalescent COVID-19 patients had only low titers of neutralizing antibodies (ND50 < 320). The sera of convalescent COVID-19 patients also neutralized pseudotype virus displaying the SARS-CoV-1 spike protein on their surface, which is homologous to the SARS-CoV-2 spike protein. In summary, we report a robust virus-neutralization assay, which can be used at low biosafety level 1 to rapidly quantify SARS-CoV-2-neutralizing antibodies in convalescent COVID-19 patients and vaccinated individuals.

scholarly journals Vesicular stomatitis virus vectors expressing avian influenza H5 HA induce cross-neutralizing antibodies and long-term protection

Virology ◽  
2007 ◽  
Vol 366 (1) ◽  
pp. 166-173 ◽  
Author(s):  
Jennifer A. Schwartz ◽  
Linda Buonocore ◽  
Anjeanette Roberts ◽  
Amorsolo Suguitan ◽  
Darwyn Kobasa ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibodies ◽  
Virus Vectors ◽  
Vesicular Stomatitis

scholarly journals Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19: Protection of mice after a single immunization

2021 ◽  
Vol 17 (4) ◽  
pp. e1009064
Author(s):  
Alexandru A. Hennrich ◽  
Bevan Sawatsky ◽  
Rosalía Santos-Mandujano ◽  
Dominic H. Banda ◽  
Martina Oberhuber ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Antigen Expression ◽  
Vaccine Platform ◽  
Dna And Rna ◽  
Glycoprotein G ◽  
Virus Like Particle ◽  
Main Target ◽  
Boost Immunization ◽  
Vesicular Stomatitis ◽  
Anchor Sequence

Vaccines of outstanding efficiency, safety, and public acceptance are needed to halt the current SARS-CoV-2 pandemic. Concerns include potential side effects caused by the antigen itself and safety of viral DNA and RNA delivery vectors. The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which might cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine complemented with VSV G, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients, and protected transgenic K18-hACE2 mice from COVID-19-like disease. Homologous boost immunization further enhanced virus neutralizing activity. The results demonstrate that non-spreading rhabdovirus RNA replicons expressing minispike proteins represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen.

Sign in / Sign up

Export Citation Format

Share Document