scholarly journals Evaluating Replication-Defective Vesicular Stomatitis Virus as a Vaccine Vehicle

2006 ◽  
Vol 80 (14) ◽  
pp. 6993-7008 ◽  
Author(s):  
Ayaz M. Majid ◽  
Heather Ezelle ◽  
Sangeeta Shah ◽  
Glen N. Barber
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Cell Activity ◽  
Recombinant Vaccinia Virus ◽  
Antibody Responses ◽  
Structural Proteins ◽  
Effective Vaccine ◽  
Murine Models ◽  
Vesicular Stomatitis ◽  
Ifn Γ ◽  
Hcv Structural Proteins

ABSTRACT We have generated replication-competent (VSV-C/E1/E2) and nonpropagating (VSVΔG-C/E1/E2) vesicular stomatitis virus (VSV) contiguously expressing the structural proteins of hepatitis C virus (HCV; core [C] and glycoproteins E1 and E2) and report on their immunogenicity in murine models. VSV-C/E1/E2 and VSVΔG-C/E1/E2 expressed high levels of HCV C, E1, and E2, which were authentically posttranslationally processed. Both VSV-expressed HCV E1-E2 glycoproteins were found to form noncovalently linked heterodimers and appeared to be correctly folded, as confirmed by coimmunoprecipitation analysis using conformationally sensitive anti-HCV-E2 monoclonal antibodies (MAbs). Intravenous or intraperitoneal immunization of BALB/c mice with VSV-C/E1/E2 or VSVΔG-C/E1/E2 resulted in significant and surprisingly comparable HCV core or E2 antibody responses compared to those of control mice. In addition, both virus types generated HCV C-, E1-, or E2-specific gamma interferon (IFN-γ)-producing CD8+ T cells, as determined by enzyme-linked immunospot (ELISPOT) analysis. Mice immunized with VSVΔG-C/E1/E2 were also protected against the formation of tumors expressing HCV E2 (CT26-hghE2t) and exhibited CT26-hghE2t-specific IFN-γ-producing and E2-specific CD8+ T-cell activity. Finally, recombinant vaccinia virus (vvHCV.S) expressing the HCV structural proteins replicated at significantly lower levels when inoculated into mice immunized with VSV-C/E1/E2 or VSVΔG-C/E1/E2, but not with control viruses. Our data therefore illustrate that potentially safer replication-defective VSV can be successfully engineered to express high levels of antigenically authentic HCV glycoproteins. In addition, this strategy may therefore serve in effective vaccine and immunotherapy-based approaches to the treatment of HCV-related disease.

scholarly journals Generation of Hepatitis C Virus-Like Particles by Use of a Recombinant Vesicular Stomatitis Virus Vector

2002 ◽  
Vol 76 (23) ◽  
pp. 12325-12334 ◽  
Author(s):  
Heather J. Ezelle ◽  
Dubravka Markovic ◽  
Glen N. Barber
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Vesicular Stomatitis Virus ◽  
Etiologic Agent ◽  
Hcv Infection ◽  
Structural Proteins ◽  
Coding Region ◽  
Vesicular Stomatitis ◽  
Hcv Structural Proteins

ABSTRACT Hepatitis C virus (HCV), a major etiologic agent of hepatocellular carcinoma, presently infects approximately 400 million people worldwide, making the development of protective measures against HCV infection a key objective. Here we have generated a recombinant vesicular stomatitis virus (VSV), which expresses the HCV structural proteins, by inserting the contiguous Core, E1, and E2 coding region of HCV into the VSV genome. Recombinant VSV expressing HCV Core, E1, and E2 (VSV-HCV-C/E1/E2) grew to high titers in vitro and efficiently expressed the incorporated HCV gene product, which became fully processed into the individual HCV structural proteins. Biochemical and biophysical analysis indicated that the HCV Core, E1, and E2 proteins assembled to form HCV-like particles (HCV-LPs) possessing properties similar to the ultrastructural properties of HCV virions. Mice immunized with VSV-HCV-C/E1/E2 generated cell-mediated immune responses to all of the HCV structural proteins, and humoral responses, particularly to E2, were also readily evident. Our data collectively indicate that engineered VSVs expressing HCV Core, E1, and E2 and/or HCV-LPs represent useful tools in vaccine and immunotherapeutic strategies designed to address HCV infection.

scholarly journals IFN-I Independent Antiviral Immune Response to Vesicular Stomatitis Virus Challenge in Mouse Brain

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 326
Author(s):  
Anurag R. Mishra ◽  
Siddappa N. Byrareddy ◽  
Debasis Nayak
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Vesicular Stomatitis Virus ◽  
Antiviral Response ◽  
Type I ◽  
Immune Gene ◽  
Antiviral Immune Response ◽  
Virus Challenge ◽  
Vesicular Stomatitis ◽  
Ifn Γ

Type I interferon (IFN-I) plays a pivotal role during viral infection response in the central nervous system (CNS). The IFN-I can orchestrate and regulate most of the innate immune gene expression and myeloid cell dynamics following a noncytopathic virus infection. However, the role of IFN-I in the CNS against viral encephalitis is not entirely clear. Here we have implemented the combination of global differential gene expression profiling followed by bioinformatics analysis to decipher the CNS immune response in the presence and absence of the IFN-I signaling. We observed that vesicular stomatitis virus (VSV) infection induced 281 gene changes in wild-type (WT) mice primarily associated with IFN-I signaling. This was accompanied by an increase in antiviral response through leukocyte vascular patrolling and leukocyte influx along with the expression of potent antiviral factors. Surprisingly, in the absence of the IFN-I signaling (IFNAR−/− mice), a significantly higher (1357) number of genes showed differential expression compared to the WT mice. Critical candidates such as IFN-γ, CCL5, CXCL10, and IRF1, which are responsible for the recruitment of the patrolling leukocytes, are also upregulated in the absence of IFN-I signaling. The computational network analysis suggests the presence of the IFN-I independent pathway that compensates for the lack of IFN-I signaling in the brain. The analysis shows that TNF-α is connected maximally to the networked candidates, thus emerging as a key regulator of gene expression and recruitment of myeloid cells to mount antiviral action. This pathway could potentiate IFN-γ release; thereby, synergistically activating IRF1-dependent ISG expression and antiviral response.

Interactions of Vesicular Stomatitis Virus Structural Proteins with HeLa Plasma Membranes

1971 ◽  
Vol 231 (21) ◽  
pp. 121-123 ◽  
Author(s):  
GERALDINE H. COHEN ◽  
PAUL H. ATKINSON ◽  
DONALD F. SUMMERS
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Plasma Membranes ◽  
Structural Proteins ◽  
Vesicular Stomatitis

scholarly journals LLOVIU VIRUS - A NOVEL FILOVIRUS, ENDEMIC IN EUROPE

2018 ◽  
Vol 63 (2) ◽  
pp. 58-61
Author(s):  
T. E. Sizikova ◽  
V. N. Lebedev ◽  
N. V. Karulina ◽  
S. V. Borisevich
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Biological Properties ◽  
Human Cells ◽  
Structural Proteins ◽  
The Novel ◽  
Virus Family ◽  
Vesicular Stomatitis ◽  
Novel Agent ◽  
Recombinant Vectors

The data on a recently revealed novel filovirus (Lloviu virus, family Filoviridae, genera Cuevavirus) in Europe are viewed in this issue. The molecular-biological properties of genome fragments of Lloviu virus were isolated from perished bats (Miniopterus sсhreibersii). Because infectious Lloviu virus has not been isolated yet, the capacity of virus to infect cells of different species and its potential to cause disease in humans is unclear. The recombinant vectors (vesicular stomatitis virus and plasmids) expressing structural proteins of Lloviu virus were used to study different elements of the virus. The question of interaction of structural proteins of Lloviu virus expressed by recombinant vectors with receptors of bat and human cells is considered. The possibility of pathogenicity of the novel agent for humans is considered. The conclusion is made about the necessity of continuous epidemical and epizootical monitoring of the new filovirus infection.

Induction of protective immune responses against a lethal Zika virus challenge post-vaccination with a dual serotype of recombinant vesicular stomatitis virus carrying the genetically modified Zika virus E protein gene

2021 ◽  
Vol 102 (4) ◽  
Author(s):  
Jung Ah Choi ◽  
Kunyu Wu ◽  
Gyoung Nyoun Kim ◽  
Nasrin Saeedian ◽  
Seung Han Seon ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vesicular Stomatitis Virus ◽  
Zika Virus ◽  
Protein Gene ◽  
Transmembrane Domain ◽  
Genetically Modified ◽  
Lethal Dose ◽  
Effective Vaccine ◽  
E Protein ◽  
Vesicular Stomatitis

The development of a vaccine to prevent Zika virus (ZIKV) infection has been one of the priorities in infectious disease research in recent years. There have been numerous attempts to develop an effective vaccine against ZIKV. It is imperative to choose the safest and the most effective ZIKV vaccine from all candidate vaccines to control this infection globally. We have employed a dual serotype of prime-boost recombinant vesicular stomatitis virus (VSV) vaccine strategy, to develop a ZIKV vaccine candidate, using a type 1 IFN-receptor knock-out (Ifnar −/−) mouse model for challenge studies. Prime vaccination with an attenuated recombinant VSV Indiana serotype (rVSVInd) carrying a genetically modified ZIKV envelope (E) protein gene followed by boost vaccination with attenuated recombinant VSV New Jersey serotype (rVSVNJ) carrying the same E gene induced robust adaptive immune responses. In particular, rVSV carrying the ZIKV E gene with the honeybee melittin signal peptide (msp) at the N terminus and VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the C terminus of the E gene induced strong protective immune responses. This vaccine regimen induced highly potent neutralizing antibodies and T cell responses in the absence of an adjuvant and protected Ifnar -/- mice from a lethal dose of the ZIKV challenge.

scholarly journals Virus-replicating T cells in the immune response of mice. II. Characterization of T cells capable of replicating vesicular stomatitis virus.

1978 ◽  
Vol 148 (4) ◽  
pp. 837-849 ◽  
Author(s):  
N Minato ◽  
Y Katsura
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Population ◽  
Vesicular Stomatitis Virus ◽  
Major Part ◽  
Cell Activity ◽  
Helper T Cells ◽  
Suppressor T Cells ◽  
Helper T Cell ◽  
Vesicular Stomatitis

Immunocytological properties of the splenic T cell (Tv) which develop into virus plaque-forming cells in response to the antigenic challenge in vitro were investigated in relation to the properties of helper T cells and suppressor T cells in antibody response. Tv was observed in spleen around 1 wk after the intravenous injection of mice with 10(7) sheep erythrocytes. This contrasted with the finding that both helper T cells and suppressor T cells developed as early as 3 days after the immunization. Tv was proliferative in response to the antigenic stimulation, whereas helper T-cell activity could be expressed without cell division. Development of Tv to virus plaque-forming cells was much more dependent on macrophages than the generation of helper activity. Tv was found in nylon wool adherent fraction, whereas helper T cell was found in both nylon adherent and nonadherent fractions. Tv belongs to the short-lived and nonrecirculating T-cell population (T1), whereas the major part of helper T cells belongs to the long-lived and recirculating T-cell population (T2). These results strongly suggest that vesicular stomatitis virus infect and replicate in the different subset(s) of T cell(s) to which the major part of helper T cells belong.

scholarly journals Evaluation of a novel vesicular stomatitis virus pseudotype-based assay for detection of neutralizing antibody responses to SARS-CoV

2006 ◽  
Vol 78 (12) ◽  
pp. 1509-1512 ◽  
Author(s):  
Shuetsu Fukushi ◽  
Tetsuya Mizutani ◽  
Masayuki Saijo ◽  
Ichiro Kurane ◽  
Fumihiro Taguchi ◽  
...  
Keyword(s):  
Vesicular Stomatitis Virus ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Vesicular Stomatitis

scholarly journals The Effect of IFN-γ, Alum and Complete Freund Adjuvant on TNP-KLH Induced Ig.G1, IgE and IgG2aResponses in Mice

1994 ◽  
Vol 3 (5) ◽  
pp. 387-392 ◽  
Author(s):  
R. van Ommen ◽  
A. E. C. M. Vredendaal ◽  
M. de Gooyer ◽  
A. van Oudenaren ◽  
H. F. J. Savelkoul
Keyword(s):  
Cytokine Production ◽  
Cell Activity ◽  
Antibody Responses ◽  
Spleen Cells ◽  
Con A ◽  
T Cell Stimulation ◽  
Ifn Γ ◽  
Serum Total Ige ◽  
Th 1

Adjuvants are considered to play an important role in directing the isotype and amount of antibodies produced upon immunization by conducting the development of either Th-1 or Th-2 cells upon T-cell stimulation. This is based on the different cytokine production patterns that were observed afterin vitroresttmulation of T cells isolated from mice immunized with antigen either adsorbed on alum or emulsified in complete Freund adjuvant (CFA). However, other studies suggest that primarily the type of antigen determines which isotypes are produced and to what extent. In these studies, however, IgE was not determined. Therefore, this study examined whether alum and CFA influenced the amount and/or ratio of IgG1, IgE and IgG2aproduced after TNP-KLH immunization. Similar levels of IgG1, IgE and IgG2aantibodies were found upon immunization with TNP-KLH either adsorbed on alum or emulsified in CFA. Moreover, administration of IFN-γ in combination with TNP-KLH adsorbed on alum did not increase the amount of IgG2aproduced. IFN-γ treatment resulted in an increased IL-6 and decreased IFN-γ production by spleen cells upon Con A stimulation, whereas it did not change the IL-4 production in similar conditions. The presented results suggest that upon immunization with TNP-KLH high IL-4 levels are produced, resulting in an antibody response that is dominated by IgG1, independent of the adjuvant employed. The IL-4 inducing property of TNP-KLH is substantiated by the finding that repeated immunization of mice with TNP-KI, without adjuvant, increases the serum total IgE level. The presented data suggest that the carrier part of TNP-KLH preferentially results in Th-2 cell activity after which the adjuvant merely enhances the antibody responses generated.

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