Immune Responses of Cattle and Mice to the G Glycoprotein of Vesicular Stomatitis Virus

Author(s):  
Tilahun Yilma ◽  
Roger G. Breeze ◽  
Sandra Ristow ◽  
John R. Gorham ◽  
Steve R. Leib
2006 ◽  
Vol 80 (9) ◽  
pp. 4447-4457 ◽  
Author(s):  
Robert J. Natuk ◽  
David Cooper ◽  
Min Guo ◽  
Priscilla Calderon ◽  
Kevin J. Wright ◽  
...  

ABSTRACT Recombinant vesicular stomatitis virus (rVSV) vectors offer an attractive approach for the induction of robust cellular and humoral immune responses directed against human pathogen target antigens. We evaluated rVSV vectors expressing full-length glycoprotein D (gD) from herpes simplex virus type 2 (HSV-2) in mice and guinea pigs for immunogenicity and protective efficacy against genital challenge with wild-type HSV-2. Robust Th1-polarized anti-gD immune responses were demonstrated in the murine model as measured by induction of gD-specific cytotoxic T lymphocytes and increased gamma interferon expression. The isotype makeup of the serum anti-gD immunoglobulin G (IgG) response was consistent with the presence of a Th1-CD4+ anti-gD response, characterized by a high IgG2a/IgG1 IgG subclass ratio. Functional anti-HSV-2 neutralizing serum antibody responses were readily demonstrated in both guinea pigs and mice that had been immunized with rVSV-gD vaccines. Furthermore, guinea pigs and mice were prophylactically protected from genital challenge with high doses of wild-type HSV-2. In addition, guinea pigs were highly protected against the establishment of latent infection as evidenced by low or absent HSV-2 genome copies in dorsal root ganglia after virus challenge. In summary, rVSV-gD vectors were successfully used to elicit potent anti-gD Th1-like cellular and humoral immune responses that were protective against HSV-2 disease in guinea pigs and mice.


2020 ◽  
Author(s):  
Xiaojuan Xue ◽  
Zhaorong Yu ◽  
Hongyan Jin ◽  
Lin Liang ◽  
Jiayang Li ◽  
...  

Abstract Background: With a human type 5 replication-defective adenovirus expression vector, we constructed the three recombinant adenoviruses (rAd) and expressed the Vesicular Stomatitis Virus (VSV) Indiana serotype glycoprotein (VSV-IN-G), VSV New Jersey serotype glycoprotein (VSV-NJ-G), and the G fusion protein [two serotypes G (VSV-IN-G-NJ-G)]. Three rAds were named rAd-IN, rAd-NJ, and rAd-IN-NJ. The three rAds were inoculated into AAV-293 cells, and the AAV-293 cells were serially propagated to 20 generations until the virus titers were stable, then TCID50 was determined. In direct immunofluorescence and western blot were used for detecting the expression of the target proteins and lymphocyte proliferation test was used for immune cell numbers. Results: The results showed that G proteins we expressed with good reactogenicity. The rAds were used to subcutaneously inoculate mice three times with 2-week intervals, and goats two times with 3-week intervals, respectively. On 0, 2, 4, and 6 weeks of post-inoculation for the mice and 0, 3, 6, 9, and 12 weeks for goats, their sera were collected and NT antibodies were determined. The results showed that the rAds could induce the production of VSV antibodies in the mice, and VSV NT antibodies in the goats. The antibody levels were 1:16 to 1: 32 in mice, and 1:32 to 1: 64 in the goats. The rAds induced strong immune lymphocyte proliferations in mice and goats, which was significantly higher than those of the negative control groups. Conclusion: The three rAds expressed VSV-G proteins at high levels, and induced humoral and cellular immune responses in both mice and goats, which laid a foundation for further studies of the recombinant adenovirus vaccines expressing VSV glycoprotein.


2021 ◽  
Author(s):  
Mijia Lu ◽  
Yuexiu Zhang ◽  
Piyush Dravid ◽  
Anzhong Li ◽  
Cong Zeng ◽  
...  

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.


2021 ◽  
Vol 102 (4) ◽  
Author(s):  
Jung Ah Choi ◽  
Kunyu Wu ◽  
Gyoung Nyoun Kim ◽  
Nasrin Saeedian ◽  
Seung Han Seon ◽  
...  

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.


2020 ◽  
Vol 18 (8) ◽  
pp. 1232-1243 ◽  
Author(s):  
Thirupandiyur S. Udayakumar ◽  
Dillon M. Betancourt ◽  
Anis Ahmad ◽  
Wensi Tao ◽  
Tulasigeri M. Totiger ◽  
...  

2005 ◽  
Vol 79 (21) ◽  
pp. 13231-13238 ◽  
Author(s):  
Jean Publicover ◽  
Elizabeth Ramsburg ◽  
John K. Rose

ABSTRACT Live attenuated vaccine vectors based on recombinant vesicular stomatitis virus (VSV) are effective in several viral disease models. In this study, we asked if a VSV vector capable of only a single cycle of replication might be an effective alternative to replication-competent VSV vectors. We compared the cellular immune responses to human immunodeficiency virus (HIV) envelope protein (Env) expressed by replication-competent and single-cycle VSV vectors and also examined the antibody response to Env. The single-cycle vector was grown by complementation with VSV G protein and then tested initially for immunogenicity when given by four different routes. When given by the intramuscular route in mice, we found that the single-cycle vector was equivalent to the replication-competent VSV vector in generating high-level primary and memory CD8 T-cell responses as well as antibody responses to Env. Cellular responses were analyzed using major histocompatibility complex class I tetramers and direct measurement of cytotoxic T-lymphocyte activity in vivo. We also found that the recall responses after boosting were equivalent in animals vaccinated with replication-competent or single-cycle vectors. Additionally, we observed recall and heightened memory responses after boosting animals with a single-cycle vector complemented with G protein from a different vesiculovirus. Because expression of HIV Env by G-deleted VSV might allow replication in human cells expressing CD4, we generated a single-cycle VSV recombinant expressing a secreted form of the HIV Env protein. This virus was just as effective as the recombinant expressing the membrane-anchored Env protein at producing CD8 T cells and antibody responses.


2007 ◽  
Vol 82 (1) ◽  
pp. 207-219 ◽  
Author(s):  
David Cooper ◽  
Kevin J. Wright ◽  
Priscilla C. Calderon ◽  
Min Guo ◽  
Farooq Nasar ◽  
...  

ABSTRACT Recombinant vesicular stomatitis virus (rVSV) has shown great potential as a new viral vector for vaccination. However, the prototypic rVSV vector described previously was found to be insufficiently attenuated for clinical evaluation when assessed for neurovirulence in nonhuman primates. Here, we describe the attenuation, neurovirulence, and immunogenicity of rVSV vectors expressing human immunodeficiency virus type 1 Gag. These rVSV vectors were attenuated by combinations of the following manipulations: N gene translocations (N4), G gene truncations (CT1 or CT9), noncytopathic M gene mutations (Mncp), and positioning of the gag gene into the first position of the viral genome (gag1). The resulting N4CT1-gag1, N4CT9-gag1, and MncpCT1-gag1 vectors demonstrated dramatically reduced neurovirulence in mice following direct intracranial inoculation. Surprisingly, in spite of a very high level of attenuation, the N4CT1-gag1 and N4CT9-gag1 vectors generated robust Gag-specific immune responses following intramuscular immunization that were equivalent to or greater than immune responses generated by the more virulent prototypic vectors. MncpCT1-gag1 also induced Gag-specific immune responses following intramuscular immunization that were equivalent to immune responses generated by the prototypic rVSV vector. Placement of the gag gene in the first position of the VSV genome was associated with increased in vitro expression of Gag protein, in vivo expression of Gag mRNA, and enhanced immunogenicity of the vector. These findings demonstrate that through directed manipulation of the rVSV genome, vectors that have reduced neurovirulence and enhanced immunogenicity can be made.


2006 ◽  
Vol 81 (4) ◽  
pp. 2078-2082 ◽  
Author(s):  
Ian D. Simon ◽  
Jean Publicover ◽  
John K. Rose

ABSTRACT Live-attenuated vesicular stomatitis virus (VSV) vectors expressing foreign antigens induce potent immune responses and protect against viral diseases in animal models. Highly attenuated (VSV-CT1) or single-cycle VSV (VSVΔG) vectors induce immune responses lower than those generated by attenuated wild-type VSV vectors when given intranasally. We show here that reduced spread of the more highly attenuated or single-cycle vectors to other organs, including lymph nodes, correlates with the reduction in the immune responses. A reverse transcription, real-time PCR assay for VSV genomic RNA (gRNA) sequences showed long-term persistence of gRNA from replicating vectors in lymph nodes, long after viral clearance. Such persistence may be important for induction of potent immune responses by VSV vectors.


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