Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonreplicating vectors are being considered in HIV-1 vaccine design. However, nonreplicating viruses are typically weak immunogens, leading to efforts to target the vaccine to mature dendritic cells (DCs). We have studied a single-cycle form of HIV-1, prepared by pseudotyping envelope-defective HIV-1 plasmids with the envelope from vesicular stomatitis virus (VSV) G protein (VSV-G), to which most humans lack preexisting immunity. The nonreplicating, VSV/HIV-1 efficiently infected the immature stage of DC development, in this case represented by monocytes cultured with GM-CSF and IL-4. A majority of the cells reverse transcribed the HIV-1 RNA, and a minority expressed gag protein. The infected populations were further matured with CD40 ligand, leading to strong stimulation of autologous T cells from HIV-1-infected individuals, but not controls. Enriched CD8(+) T cells from 12/12 donors released IFN-gamma (50-300 enzyme-linked immunospots/200,000 T cells) and proliferated. Macrophages were much less efficient in expanding HIV-1-responsive T cells, and bulk mononuclear cells responded weakly to VSV/HIV-1. CD4(+) T cells from at least half of the donors showed strong responses to VSV/HIV-1-infected DCs. Presentation to CD8(+) T cells, but not to CD4(+), was primarily through an endogenous pathway, because the responses were markedly reduced if envelope-defective virus particles or reverse transcriptase inhibitors were added. Therefore, nonreplicating vaccines can be targeted to immature DCs, which upon further maturation induce combined and robust CD4(+) and CD8(+) immunity.
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PMID:Dendritic cells, infected with vesicular stomatitis virus-pseudotyped HIV-1, present viral antigens to CD4+ and CD8+ T cells from HIV-1-infected individuals. 1108 7

Non-infectious, envelope protein-free, retrovirus-like particles (VLP) derived from either Moloney murine leukemia virus (MLV) or human HIV are able to bind efficiently to, but not infect, target cells. Upon subsequent addition to the bound particles of the G protein of vesicular stomatitis virus (VSV-G), an efficient surrogate retrovirus envelope protein, the VLP are efficiently taken up by the cells to produce infection. Cell attachment of the VLP is efficiently inhibited by soluble heparin and dextran sulfate and less efficiently abrogated by several other glycosaminoglycans (GAGs) including chondroitin sulfate A and chondroitin sulfate B (dermatan sulfate), as determined by deconvolution microscopic immunodetection of the viral gag protein and by quantitative binding studies of metabolically labeled (35)S-VLP. Enzymatic digestion of heparan sulfate (HS) from the cell surface with heparinase I also reduces VLP binding. Furthermore, VLP adsorption onto several CHO cell lines variably deficient in cell surface GAG is significantly but incompletely abrogated. De-sulfated heparins are less efficient than native heparin in inhibiting the Polybrene-mediated binding of VLP, whereas growth of human cells in the presence of sodium chlorate leads to significant reduction of Polybrene-mediated VLP binding. In addition, specific inhibition of VLP binding and infectivity of mature infectious VSV-G-pseudotyped virus is observed in the presence of heparin and HS under Polybrene-free conditions. We conclude from these studies that the presence of Polybrene, the degree of sulfation of cell surface GAG, and possibly the presence of charged cell surface macromolecules create an electrostatic environment that promotes optimum binding of VLP to cells. Additionally, our results demonstrate that, in the absence of Polybrene, initial attachments of non-infectious, envelope protein-free VLP and probably mature infectious virus particles are mediated by interactions of the virus particles with cell surface heparan sulfate, and possibly with other GAG molecules.
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PMID:Cell surface heparan sulfate is a receptor for attachment of envelope protein-free retrovirus-like particles and VSV-G pseudotyped MLV-derived retrovirus vectors to target cells. 1199 44

Assessment of in vivo viral replication of live attenuated recombinant vesicular stomatitis virus (rVSV) vaccine vector candidates encoding HIV gag requires comprehensive preclinical safety studies, and development of sensitive assays to monitor the outcome of vaccination of animals is important. In this study, two 2-step quantitative real-time RT-PCR assays were developed; a singleplex assay to detect VSV genomic RNA from ferrets inoculated intra-cranially (IC) or intra-nasally (IN) with either a wild-type (wt) virus or an attenuated rVSV vector engineered to express HIV gag protein, and a duplex assay to simultaneously detect VSV-N and HIV-gag mRNAs from cynomolgus macaques inoculated intra-thalamically (IT) with the same viruses. Using synthetic oligonucleotides as standards, the lower limit of detection of VSV-N and HIV-gag was 50 copies. Results showed high levels of wt VSV(IN) genomic RNA and mRNA in ferret and macaque tissues, respectively, and significantly lower levels of VSV genomic RNA and VSV-N and HIV-gag mRNAs in tissues from animals inoculated with the attenuated rVSV vector. These assays correlated with both the course of infection for these animals, and the infectious viral load measured by a standard plaque assay, and could be used to determine the safety profile of rVSV vaccine vectors.
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PMID:Quantitative multiplex assay for simultaneous detection of the Indiana serotype of vesicular stomatitis virus and HIV gag. 1738 12

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viral and other microbial pathogens in their genome (so-called "chimeric virus vaccines"). Many such viral vector vaccines are now at various stages of clinical evaluation. Here, we introduce an attenuated form of recombinant vesicular stomatitis virus (rVSV) as a potential chimeric virus vaccine for HIV-1, with implications for use as a vaccine vector for other pathogens. The rVSV/HIV-1 vaccine vector was attenuated by combining two major genome modifications. These modifications acted synergistically to greatly enhance vector attenuation and the resulting rVSV vector demonstrated safety in sensitive mouse and non-human primate neurovirulence models. This vector expressing HIV-1 gag protein has completed evaluation in two Phase I clinical trials. In one trial the rVSV/HIV-1 vector was administered in a homologous two-dose regimen, and in a second trial with pDNA in a heterologous prime boost regimen. No serious adverse events were reported nor was vector detected in blood, urine or saliva post vaccination in either trial. Gag specific immune responses were induced in both trials with highest frequency T cell responses detected in the prime boost regimen. The rVSV/HIV-1 vector also demonstrated safety in an ongoing Phase I trial in HIV-1 positive participants. Additionally, clinical trial material has been produced with the rVSV vector expressing HIV-1 env, and Phase I clinical evaluation will initiate in the beginning of 2016. In this paper, we use a standardized template describing key characteristics of the novel rVSV vaccine vectors, in comparison to wild type VSV. The template facilitates scientific discourse among key stakeholders by increasing transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines.
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PMID:Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk/benefit assessment. 2739 63