Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “VACCINIA”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1984

Additional evidence for the augmented induction of tumor-specific resistance in vaccinia virus-primed mice by immunization with vaccinia virus-modulated syngeneic tumor cells.

The augmenting effect of vaccinia virus infection of tumor cells on induction of tumor-specific resistance was examined in mice. C3H/HeN mice were primed intraperitoneally (ip) with live vaccinia virus after whole-body irradiation with 250 rad of X-rays. Three weeks later the mice were immunized ip 3 times at weekly intervals with syngeneic murine hepatoma MH134 or spontaneous myeloma X5563 which had been infected in vitro with vaccinia virus and subsequently irradiated with 7000 rad of X-rays. One week after the third immunization, the mice were challenged with 1 X 10(5) viable cells of MH134 or X5563 ip or 1 X 10(6) tumor cells intradermally (id). On ip challenge with viable MH134 cells all mice that had not been pretreated died within 3 weeks due to ascites tumor out-growth, whereas all mice that had been vaccinia virus-primed and immunized with vaccinia virus-infected MH134 cells survived. On ip challenge with X5563 cells, the percentage survival of vaccinia virus-primed and vaccinia virus-modified tumor-immunized mice was 80%. On id challenge with MH134 and X5563 tumor cells, in un-treated mice tumors grew to more than 5 mm in diameter within 3 weeks, whereas 90% and 60%, respectively, of the mice that had been vaccinia virus-primed and immunized with vaccinia virus-infected tumor cells showed no tumor out-growth. Pretreatment by only immunization with vaccinia virus-infected cells or vaccinia virus-priming and immunization with virus non-infected tumor cells were not effective for preventing induction of tumor-resistance to either ip or id challenge with MH134 or X5563 tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Therapeutic effect of a vaccinia colon oncolysate prepared with interleukin-2-gene encoded vaccinia virus studied in a syngeneic CC-36 murine colon hepatic metastasis model.

Vaccinia CC-36 murine colon oncolysate (VCO) prepared with interleukin-2-gene encoded recombinant vaccinia virus (IL-2VCO) was used in the treatment of a syngeneic murine colon adenocarcinoma (CC-36) hepatic metastasis to test the beneficial effect of the interleukin-2-gene encoded vaccinia virus over a control recombinant vaccinia virus in producing a vaccinia oncolysate tumor cell vaccine. Results suggest that the IL-2VCO treatment significantly reduced the hepatic tumor burden in comparison with the controls that received either IL-2-gene-encoded recombinant vaccinia virus or a plain recombinant vaccinia virus or vaccinia oncolysate prepared with the plain recombinant virus. The survival of mice treated with IL-2VCO was also improved in comparison with mice treated with other preparations. The induction of a cytolytic T lymphocyte response was examined to elucidate the mechanism of the induction of antitumor responses in IL-2VCO-treated mice. Fresh peripheral blood lymphocytes (PBL) isolated from IL-2VCO-treated mice showed a higher cytolytic activity against CC-36 tumor cell target when compared to PBL from the mice of other treatment groups, suggesting that the IL-2VCO induced an antitumor cytolytic T lymphocyte response. These results suggest that a vaccinia oncolysate, prepared with recombinant vaccinia virus encoding an immunomodulating cytokine gene will enhance antitumor responses in the host.

Adenocarcinoma↗
PubMed1975

Vaccinia virus infection of HeLa cells. I. Synthesis of vaccinia DNA in host cell nuclei.

The replication of vaccinia virus is thought to take place exclusively in the cytoplasm of host cells. However, using DNA-DNA hybridization techniques, it can be shown that a significant fraction of the synthesis of vaccinia DNA takes place in the nucleus as well as the cytoplasm. The (3H) thymiding pulse-labeled vaccinia DNA synthesized in the nucleus reaches a maximum at about 3 h after infection, corresponding to the time of maximal DNA synthesis in infected cells. At this time host DNA synthesis drops to about 25% of the rate of the uninfected cells. Even with short labeling times (2 min) the nucleus is found to contain 60% of the incorporated (3H)thymidine, much of which is in vaccinia DNA. Prior inhibition of host nuclear DNA synthesis with mitomycin C, followed by removal of the antibiotic causes a subsequent inhibition of vaccinia DNA synthesis and complete suppression of mature virus. Purified nuclei, isolated from vaccinia-infected cells, also synthesize vaccinia DNA in vitro. Over 90% of the DNA synthesized in vitro by isolated nuclei contain vaccinia-specific sequences.

Cell Fractionation↗
PubMed1985

In vitro transcription of a cloned vaccinia virus gene by a soluble extract prepared from vaccinia virus-infected HeLa cells.

Faithful transcription of a vaccinia virus gene was accomplished in vitro by using a soluble extract prepared from vaccinia virus-infected HeLa cells. Specific transcription of the cloned vaccinia virus gene was detected by using template DNA restricted within the transcribed region. The vaccinia virus gene was not transcribed by extracts prepared from uninfected HeLa cells even with supplementation by purified vaccinia virus RNA polymerase, nor was a clone of adenovirus 2 DNA bearing the major late promoter transcribed by the extract from vaccinia virus-infected HeLa cells. Thus, infection by vaccinia virus altered cellular transcriptional specificity to favor expression of vaccinia virus genes. RNA synthesis by the infected cell extract was resistant to alpha-amanitin but strongly inhibited by beta, gamma-imido ATP and novobiocin.

Adenoviridae↗
PubMed2002

Immunogenicity and safety of defective vaccinia virus lister: comparison with modified vaccinia virus Ankara.

Potent and safe vaccinia virus vectors inducing cell-mediated immunity are needed for clinical use. Replicating vaccinia viruses generally induce strong cell-mediated immunity; however, they may have severe adverse effects. As a vector for clinical use, we assessed the defective vaccinia virus system, in which deletion of an essential gene blocks viral replication, resulting in an infectious virus that does not multiply in the host. The vaccinia virus Lister/Elstree strain, used during worldwide smallpox eradication, was chosen as the parental virus. The immunogenicity and safety of the defective vaccinia virus Lister were evaluated without and with the inserted human p53 gene as a model and compared to parallel constructs based on modified vaccinia virus Ankara (MVA), the present "gold standard" of recombinant vaccinia viruses in clinical development. The defective viruses induced an efficient Th1-type immune response. Antibody and cytotoxic-T-cell responses were comparable to those induced by MVA. Safety of the defective Lister constructs could be demonstrated in vitro in cell culture as well as in vivo in immunodeficient SCID mice. Similar to MVA, the defective viruses were tolerated at doses four orders of magnitude higher than those of the wild-type Lister strain. While current nonreplicating vectors are produced mainly in primary chicken cells, defective vaccinia virus is produced in a permanent safety-tested cell line. Vaccines based on this system have the additional advantage of enhanced product safety. Therefore, a vector system was made which promises to be a valuable tool not only for immunotherapy for diseases such as cancer, human immunodeficiency virus infection, or malaria but also as a basis for a safer smallpox vaccine.

Animals↗
PubMed1984

Translation of vaccinia virus and cellular mRNA in cell-free systems prepared from uninfected and vaccinia virus infected L929 cells.

Cell-free translation systems were prepared from uninfected and vaccinia infected (3 and 5 hours post-infection) L929 cells. The systems were made mRNA dependent in order to translate exogenous mRNA mixtures. The overall rate of protein synthesis was similar in the three translation systems. However, one-dimensional electrophoresis showed that the systems differed in terms of the translation efficiency for individual mRNAs. This could be demonstrated with each of the following mRNA mixtures: early vaccinia mRNA synthesized by vaccinia cores in vitro, mRNA isolated from polysomes of vaccinia infected HeLa cells ("late" vaccinia mRNA) and cytoplasmic ascites mRNA. When the above mentioned groups of mRNAs were allowed to compete for translation in the cell-free systems and their products were analyzed on one-dimensional gels, the following order of translational efficiency was observed: the most prominent species of vaccinia early mRNA (other species could not be judged) were translated better than some late vaccinia mRNA species which in turn were slightly more efficiently translated than cellular mRNAs.

Animals↗
PubMed2001

Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes.

We have demonstrated previously the oncolytic effects of a systemically delivered, replicating vaccinia virus. To enhance the tumor specificity of this vector, we have developed a combined thymidine kinase-deleted (TK-) and vaccinia growth factor-deleted (VGF-) vaccinia virus and investigated its properties in vitro and in vivo. The gene for enhanced green fluorescent protein (EGFP) was inserted into the TK locus of a VGF- vaccinia virus by homologous recombination creating a double-deleted mutant vaccinia virus (vvDD-GFP). Infection of resting and dividing NIH3T3 cells with vvDD-GFP yielded reduced viral recovery compared with wild-type (WT), TK-, or VGF- viruses from resting cultures but equivalent virus recovery from dividing cultures. Eight days after nude mice were injected i.p. with 10(7) plaque-forming units (pfu) of WT, TK-, VGF-, or vvDD-GFP vaccinia virus, tissues and tumor were harvested for viral titer determination. No virus was recovered from the brains of mice injected with vvDD-GFP compared with the other viruses, which ranged from 130 to 28,000 pfu/mg protein; however, equivalent amounts were recovered from tumor. There was no toxicity from vvDD-GFP because nude mice receiving 10(8) pfu of IP vvDD-GFP lived >100 days, whereas mice receiving WT, VGF-, or TK- virus had median survivals of only 6, 17, and 29 days, respectively. Similar results were seen when 10(9) pfu of vvDD-GFP were given. Nude mice bearing s.c. murine colon adenocarcinoma (MC38) had significant tumor regression after treatment with 10(9) pfu of systemic (i.p.) vvDD-GFP compared with control (mean tumor size, 180.71 +/- 35.26 mm(3) versus 2796.79 +/- 573.20 mm(3) 12 days after injection of virus). Our data demonstrate that a TK- and VGF- mutant vaccinia virus is significantly attenuated in resting cells in vitro and demonstrates tumor-specific replication in vivo. It is a promising vector for use in tumor-directed gene therapy, given its enhanced safety profile, tumor selectivity, and the oncolytic effects after systemic delivery.

3T3 Cells↗
PubMed1994

Vaccinia protein kinase 2: a second essential serine/threonine protein kinase encoded by vaccinia virus.

The major protein kinase activity from vaccinia virus core particles was purified to near homogeneity. The protein kinase is a 50-kDa polypeptide that is shown here to phosphorylate primarily seryl residues in alpha-casein, a casein kinase I-specific peptide substrate, and itself through autophosphorylation. The sequence of four peptides derived from the protein kinase demonstrated that it is encoded by the vaccinia virus F10L gene. Expression of the F10L gene product in bacteria as a fusion with glutathione S-transferase confirmed that the vaccinia F10L gene encodes the protein kinase. We have termed this enzyme vaccinia protein kinase 2 (VPK2) to distinguish it from the protein kinase encoded by the vaccinia B1R gene. Targeted disruption of the VPK2 gene with a positive selectable marker demonstrated that all viruses with a disrupted gene also possessed a wild-type gene, suggesting that VPK2 is essential for viability. The discovery of a second essential protein kinase encoded by vaccinia virus, in addition to a protein phosphatase, underscores the importance of protein phosphorylation in poxvirus biogenesis.

Amino Acid Sequence↗
PubMed1992

Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network.

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) gp160 recombinant vaccinia virus (HIVAC-1e) vaccine was evaluated in vaccinia-naive, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 36) were randomized to receive HIVAC-1e or control vaccinia virus at two dosages by bifurcated needle puncture at 0 and 2 months; 12 HIVAC-1e and 6 control vaccinia virus recipients received either 10(6) or 10(7) pfu/mL at each inoculation. There was no significant difference in lesion size, level of viral replication, or systemic symptoms after vaccination with HIVAC-1e or control vaccinia virus. Of 22 HIVAC-1e recipients with lesion formation, 16 developed low-titer gp160-specific antibody responses detectable by Western blot. The peak response occurred between days 70 and 120 and was still detectable at day 365 in 9 of 18 vaccinees. gp160-specific lymphoproliferative responses were detected in 5 of 10 vaccinees. Vaccination with HIVAC-1e was safe in vaccinia-naive, healthy adults and could induce both humoral and cell-mediated gp160-specific immune responses.

AIDS Vaccines↗
PubMed2003

Vaccinia vectors as candidate vaccines: the development of modified vaccinia virus Ankara for antigen delivery.

Vaccinia viruses engineered to express foreign genes are powerful vectors for production of recombinant proteins. Originating from highly efficacious vaccines securing world-wide eradication of smallpox, the most appealing use of vaccinia vectors is to serve as vaccine delivery system for heterologous antigens. Concerns about the safety of vaccinia virus have been addressed by the development of vectors based on attenuated viruses. One of them, modified vaccinia virus Ankara (MVA) can be considered as current vaccinia virus strain of choice for clinical investigation. Historical development and use of MVA as vaccine against smallpox allowed to establish an extraordinary safety profile. MVA can be used under conditions of biosafety level 1 because of its avirulence and its deficiency to productively grow in human cells. In recent years significant progress has been made with regard to the development of MVA vector technologies. Compared to replication competent vaccinia viruses, MVA provides similar levels of recombinant gene expression even in nonpermissive cells. In animal models, MVA vaccines have been found immunogenic and protective against various infectious agents including immunodeficiency viruses, influenza, parainfluenza, measles virus, flaviviruses, or plasmodium parasites. By now first data from clinical trials are becoming available. In this article we briefly review history of MVA and state-of-the art technologies with regard to generation of recombinant MVA vaccines, and describe the progress to develop MVA vector vaccines against important infectious diseases.

Animals↗
PubMed2003

Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses.

Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naïve mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity.

Animals↗
PubMed1979

[Participation of vaccinia virus in the pathogenesis of different clinical forms of postvaccinal complications. I. Frequency of vaccinia virus detection in the vaccinted who have usual and complicated reactions to vaccination].

The virological examination of 1365 samples taken from 469 children vaccinated against smallpox revealed considerable differences in the frequency and the time of vaccinia virus detection in different clinical forms of postvaccinal pathology as compared with uncomplicated vaccinal process. During the postvaccinal period taking its normal course vaccinia virus was isolated from 7.3% of children only from the pharynx till day 8 following vaccination. In generalized and creeping vaccinia the virus was isolated from 71.4% of children, in postvaccinal encephalitis from 57.1% of children, in vaccinal angina frove-mentioned complications vaccinia virus was detected in the samples obtained from the patients till days 24, 35, 15 and 24 respectively. The etiopathogenetic role of vaccinia virus in a number of postvaccinal complications is discussed.

Child, Preschool↗
PubMed1987

Resistance of vaccinia virus to interferons: modulation of the 2-5A system in interferon-treated, vaccinia virus infected cells.

In this study we have examined if resistance of vaccinia virus to interferon (IFN) correlates with virus-induced alterations of the 2-5A system. We have shown that in various IFN-treated vaccinia virus infected cells of mouse, monkey and human origins, the intracellular levels of 2-5A are low early in infection but exhibit a sharp rise late in infection. In spite of the presence of 2-5A, activation of the 2-5A dependent RNase, as measured by the rRNA cleavage assay, does not occur or is delayed in the course of virus infection. However, when cycloheximide, an inhibitor of protein synthesis is added at the time of virus infection, extensive cleavage or rRNA is observed in IFN-treated, infected cells. If cycloheximide is added at various times after virus infection, rRNA cleavage is gradually prevented and a virus-induced inhibitor of the 2-5A system can be detected between 1-2 hr post infection. A function encoded by a ts 22 mutant of vaccinia virus blocked rRNA cleavage. Restriction of rRNA cleavage during virus infection correlated with dephosphorylation of 2-5A. Our findings suggest that modulation of the 2-5A system by vaccinia virus involves the production of an activator and simultaneous synthesis of an inhibitor(s). Viral ds-RNA is likely to be the activator while a function encoded by ts 22 mutant is involved in inhibition of the 2-5A system. Other viral functions (ATPase and phosphatase) may also be involved in modifications of the 2-5A system by regulating 2-5A levels and altering the integrity of 2-5A. Modifications of the 2-5A system, during vaccinia virus infection might contribute to the resistance of this cytoplasmic DNA virus to IFN.

2',5'-Oligoadenylate Synthetase↗
PubMedDate not supplied

Protection of vaccinia-primed macaques against SIVmne infection by combination immunization with recombinant vaccinia virus and SIVmne gp160.

Two Macaca fascicularis with preexisting immunity to vaccinia virus were immunized twice with recombinant vaccinia virus expressing SIVmne gp160. Their SIV-specific antibody responses were lower than that of vaccinia-naive animals immunized similarly. Upon repeated boosting with gp160, the SIV-specific antibody titers in vaccinia-primed animals reached similar levels as vaccinia-naive animals and with comparable neutralizing titers. Both animals were protected against repeated intravenous challenge with low-dose SIVmne E11S. These results are significant because SIVmne E11S infection in M. fascicularis is pathogenic and leads to AIDS-like diseases.

Animals↗
PubMed1989

Attenuated deletion mutants of vaccinia virus lacking the vaccinia growth factor are defective in replication in vivo.

Understanding the molecular basis of virulence in poxvirus is of great importance for the development of recombinant vaccines using vaccinia virus as a vector. We have previously described mutants of vaccinia virus with deletions ranging from 20 to 21 kb at the left terminus and with attenuated phenotype. The virulence of these mutants was studied, using different routes of inoculation, for protection from wild-type challenge in mice and for replication in vivo. Regardless of the route of inoculation, the LD50 of the deletion mutants is at least 1000-fold higher than that of the wild-type. Results from protection experiments using viable and ultraviolet-inactivated viruses, and from determination of infectivity in different organs, indicated that the mutants were unable to replicate in vivo. Southern blot hybridization of viral DNA with pSC16, a plasmid containing the vaccinia growth factor (VGF) gene, revealed that in the IHD-W strain of vaccinia virus this gene is localized at the left terminus exclusively and that the mutants lack this gene. The results suggest that absence of the VGF gene is correlated with inability to replicate in vivo and decreased virulence.

Animals↗
PubMed1973

Induction of skin resistance to vaccinia virus in rabbits by vaccinia-soluble early antigens.

The immunological role of vaccinia-soluble early antigen was examined in rabbits. The antigens were prepared from HeLa cells infected with a conditional lethal mutant of vaccinia virus, which induces in these cells early antigens including those responsible for surface immunofluorescence of infected cells, but not viral DNA and late protein syntheses. Immunization of rabbits with the antigens in Freund's complete adjuvant induced complement-fixing antibody but neither detectable circulating neutralizing antibody nor any detectable level of inhibitory substance or interferon in the skin of the animals. When immunized animals were inoculated intradermally with vaccinia virus, multiplication of virus in the skin was greatly inhibited, being accompanied by an earlier appearance as well as an accelerated wane of the local reactions. The resistance could not be transferred passively by the serum of immunized animals to normal rabbits. Immunization of rabbits with the antigens without the adjuvant not only failed to inhibit but, contrariwise, enhanced the multiplication of intradermally inoculated vaccinia virus, inducing heavy skin lesions and exalted virus multiplication.

Animals↗
PubMed1996

Active specific immunotherapy of pulmonary metastasis with vaccinia melanoma oncolysate prepared from granulocyte/macrophage-colony-stimulating-factor-gene-encoded vaccinia virus.

Vaccinia melanoma oncolysate (VMO) prepared with recombinant vaccinia virus encoding the gene of murine granulocyte/macrophage-colony-stimulating factor (GM-CSF) was tested for its therapeutic effect on melanoma pulmonary metastasis. The murine pulmonary metastasis model was established by injecting 2 x 10(5) B16F10 melanoma cells into the tail vein of a C57BL/6 mouse. Intraperitoneal injection of VMO was performed in tumor-bearing mice 3 and 10 days after B16F10 cell inoculation. The results showed that treatment with VMO prepared with GM-CSF-gene-encoded vaccinia virus (GM-CSFVMO) significantly decreased the number of murine pulmonary metastases and prolonged the survival of the tumor-bearing mice. Lymphocytes isolated from fresh blood and spleen of GM-CSFVMO-treated mice showed higher cytolytic activity against B16F10 melanoma cells when compared with lymphocytes from the mice of other treatment groups. Natural killer activity remained unchanged in the GM-CSFVMO-treated group. Cytotoxic activities of peritoneal macrophages were found to be greatly elevated in mice treated with GM-CSFVMO. Further study illustrated that the increased tumor necrosis factor and nitric oxide release from macrophages may contribute to their cytotoxic effects. These results suggest that the tumor oncolysate vaccine prepared with GM-CSF-gene-encoded vaccinia virus has a potent therapeutic effect on tumor metastasis through the efficient induction of antitumor immunity of the host, mainly through the cytotoxic effects of cytotoxic T lymphocytes and macrophages.

Animals↗