EVALUATION OF IMMUNOGENICITY AND PTOTECTIVENESS OF THE VACCINIA VIRUS LIVP-GFP IN THREE LABORATORY ANIMAL SPECIES

Smallpox eradication and absence of adequate animal model of smallpox infection causes necessity of the assessment of immunogenic and protective properties of the created by genetic engineering approaches live attenuated smallpox vaccines in several animal models of orthopoxviral infections. In this research comparison of the immunogenic and protective properties of the recombinant vaccinia virus (VACV) LIVP-GFP after intradermal (i/d) injection to mice, guinea pigs and rabbits were carried out. Doses of LIVP-GFP immunization in all animal species were 2x104 or 2x106 pfu. Control animals were injected with saline. Blood sampling was done on 28 day after virus LIVP-GFP or saline injection. Blood samples were taken intravitally from the retro-orbital venous sinus of mice, from heart of guinea pigs or marginal ear vein of rabbits. Serum was isolated from blood samples by precipitating blood cells via centrifugation. The anti-VACV IgG titers in the serum samples were determined by ELISA. On 30 day of the experiment immunized by virus LIVP-GFP or control animals were intranasal infected with lethal doses of the corresponding orthopoxviruses to which every animal species was sensitive. Mice were infected by cowpox virus (CPXV) strain GRI-90 in dose 68 LD50, guinea pigs - by VACV GPA in dose 56 LD50, rabbits – by VACV HB-92 in dose 100 LD50. All control animals after that were died, but all animals immunized by attenuated recombinant virus LIVP-GFP in dose 2x106 pfu were survived. In case of the LIVP-GFP immunization dose 2x104 pfu 88% of mice were survived after CPXV infection, 67% of rabbits were survived after VACV HB-92 infection, and 50% of guinea pigs were survived after VACV GPA infection. ELISA data of the blood serums had shown correlation of the levels of VACV-specific antibodies with levels of protection in the corresponding animals. On the basis of the obtained data it could be concluded that all three studied models animal-orthopoxvirus allow give an adequate evaluation of immunogenicity and protectiveness of the created modern attenuated vaccines against smallpox and other orthopoxviral human infections. BALB/c mice are the most convenient subject of this investigation

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IMMUNOGENIC AND PROTECTIVE PROPERTIES OF RECOMBINANT VACCINIA VIRUS STRAIN, EXPRESSING GENE CASSETTE OF MARBURG VIRUS STRUCTURAL PROTEINS

BIOTECHNOLOGY: STATE OF THE ART AND PERSPECTIVES ◽

10.37747/2312-640x-2020-18-210-212 ◽

2020 ◽

pp. 210-212

Author(s):

A. Semenova ◽

G. Sivolobova ◽

A. Grazhdantseva ◽

S. P’yankov ◽

O. Taranov ◽

...

Keyword(s):

Vaccinia Virus ◽

Guinea Pigs ◽

Gene Cassette ◽

Recombinant Vaccinia Virus ◽

Marburg Virus ◽

Structural Proteins ◽

Protective Properties ◽

Recombinant Vaccinia ◽

Lethal Infection ◽

Vaccinia Virus Strain

Based on the highly attenuated vaccinia virus MVA strain, a recombinant variant MVA-GP-VP40-MARV was constructed, which expresses a cassette of the GP and VP-40 genes of the Marburg virus with the formation of immunogenic virus-like particles and protects Guinea pigs from a lethal infection by the Marburg virus.

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Activities of Certain 5-Substituted 4′-Thiopyrimidine Nucleosides against Orthopoxvirus Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01257-08 ◽

2008 ◽

Vol 53 (2) ◽

pp. 572-579 ◽

Cited By ~ 14

Author(s):

Earl R. Kern ◽

Mark N. Prichard ◽

Debra C. Quenelle ◽

Kathy A. Keith ◽

Kamal N. Tiwari ◽

...

Keyword(s):

Vaccinia Virus ◽

Recombinant Vaccinia Virus ◽

Cowpox Virus ◽

Significant Protection ◽

Complete Protection ◽

Viral Dna ◽

Recombinant Vaccinia ◽

Significant Toxicity ◽

Resistant Mutants ◽

New Compounds

ABSTRACT As part of a program to identify new compounds that have activity against orthopoxviruses, a number of 4′-thionucleosides were synthesized and evaluated for their efficacies against vaccinia and cowpox viruses. Seven compounds that were active at about 1 μM against both viruses in human cells but that did not have significant toxicity were identified. The 5-iodo analog, 1-(2-deoxy-4-thio-β-d-ribofuranosyl)-5-iodouracil (4′-thioIDU), was selected as a representative molecule; and this compound also inhibited viral DNA synthesis at less than 1 μM but only partially inhibited the replication of a recombinant vaccinia virus that lacked a thymidine kinase. This compound retained complete activity against cidofovir- and ST-246-resistant mutants. To determine if this analog had activity in an animal model, mice were infected intranasally with vaccinia or cowpox virus and treatment with 4′-thioIDU was given intraperitoneally or orally twice daily at 50, 15, 5, or 1.5 mg/kg of body weight beginning at 24 to 120 h postinfection and was continued for 5 days. Almost complete protection (87%) was observed when treatment with 1.5 mg/kg was begun at 72 h postinfection, and significant protection (73%) was still obtained when treatment with 5 mg/kg was initiated at 96 h. Virus titers in the liver, spleen, and kidney were reduced by about 4 log10 units and about 2 log10 units in mice infected with vaccinia virus and cowpox virus, respectively. These results indicate that 4′-thioIDU is a potent, nontoxic inhibitor of orthopoxvirus replication in cell culture and experimental animal infections and suggest that it may have potential for use in the treatment of orthopoxvirus infections in animals and humans.

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Homologous and heterologous glycoproteins induce protection against Junin virus challenge in guinea pigs

Microbiology ◽

10.1099/0022-1317-81-5-1273 ◽

2000 ◽

Vol 81 (5) ◽

pp. 1273-1281 ◽

Cited By ~ 17

Author(s):

Nora López ◽

Luis Scolaro ◽

Carlos Rossi ◽

Rodrigo Jácamo ◽

Nélida Candurra ◽

...

Keyword(s):

Vaccinia Virus ◽

Guinea Pigs ◽

Neutralizing Antibodies ◽

Recombinant Vaccinia Virus ◽

Glycoprotein Precursor ◽

Lethal Challenge ◽

Recombinant Vaccinia ◽

Junin Virus ◽

Virus Challenge ◽

Junín Virus

Tacaribe virus (TACV) is an arenavirus that is genetically and antigenically closely related to Junin virus (JUNV), the aetiological agent of Argentine haemorrhagic fever (AHF). It is well established that TACV protects experimental animals fully against an otherwise lethal challenge with JUNV. To gain information on the nature of the antigens involved in cross-protection, recombinant vaccinia viruses were constructed that express the glycoprotein precursor (VV–GTac) or the nucleocapsid protein (VV–N) of TACV. TACV proteins expressed by vaccinia virus were indistinguishable from authentic virus proteins by gel electrophoresis. Guinea pigs inoculated with VV–GTac or VV–N elicited antibodies that immunoprecipitated authentic TACV proteins. Antibodies generated by VV–GTac neutralized TACV infectivity. Levels of antibodies after priming and boosting with recombinant vaccinia virus were comparable to those elicited in TACV infection. To evaluate the ability of recombinant vaccinia virus to protect against experimental AHF, guinea pigs were challenged with lethal doses of JUNV. Fifty per cent of the animals immunized with VV–GTac survived, whereas all animals inoculated with VV–N or vaccinia virus died. Having established that the heterologous glycoprotein protects against JUNV challenge, a recombinant vaccinia virus was constructed that expresses JUNV glycoprotein precursor (VV–GJun). The size and reactivity to monoclonal antibodies of the vaccinia virus-expressed and authentic JUNV glycoproteins were indistinguishable. Seventy-two per cent of the animals inoculated with two doses of VV–GJun survived lethal JUNV challenge. Protection with either VV–GJun or VV–GTac occurred in the presence of low or undetectable levels of neutralizing antibodies to JUNV.

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Construction of a recombinant vaccinia virus expressing the Lassa virus glycoprotein gene and protection of guinea pigs from a lethal Lassa virus infection

Virus Research ◽

10.1016/0168-1702(88)90033-0 ◽

1988 ◽

Vol 9 (2-3) ◽

pp. 233-248 ◽

Cited By ~ 51

Author(s):

David D. Auperin ◽

Joseph J. Esposito ◽

James V. Lange ◽

Sally P. Bauer ◽

Janice Knight ◽

...

Keyword(s):

Virus Infection ◽

Vaccinia Virus ◽

Guinea Pigs ◽

Recombinant Vaccinia Virus ◽

Lassa Virus ◽

Recombinant Vaccinia ◽

Virus Glycoprotein ◽

Glycoprotein Gene

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Infection with Foamy Virus in Wild Ruminants—Evidence for a New Virus Reservoir?

Viruses ◽

10.3390/v12010058 ◽

2020 ◽

Vol 12 (1) ◽

pp. 58

Author(s):

Magdalena Materniak-Kornas ◽

Martin Löchelt ◽

Jerzy Rola ◽

Jacek Kuźmak

Keyword(s):

Red Deer ◽

Animal Species ◽

Foamy Virus ◽

Companion Animals ◽

Genetic Material ◽

Serum Samples ◽

Blood Samples ◽

Bovine Foamy Virus ◽

Wild Ruminants ◽

Foamy Viruses

Foamy viruses (FVs) are widely distributed and infect many animal species including non-human primates, horses, cattle, and cats. Several reports also suggest that other species can be FV hosts. Since most of such studies involved livestock or companion animals, we aimed to test blood samples from wild ruminants for the presence of FV-specific antibodies and, subsequently, genetic material. Out of 269 serum samples tested by ELISA with the bovine foamy virus (BFV) Gag and Bet antigens, 23 sera showed increased reactivity to at least one of them. High reactive sera represented 30% of bison samples and 7.5% of deer specimens. Eleven of the ELISA-positives were also strongly positive in immunoblot analyses. The peripheral blood DNA of seroreactive animals was tested by semi-nested PCR. The specific 275 bp fragment of the pol gene was amplified only in one sample collected from a red deer and the analysis of its sequence showed the highest homology for European BFV isolates. Such results may suggest the existence of a new FV reservoir in bison as well as in deer populations. Whether the origin of such infections stems from a new FV or is the result of BFV inter-species transmission remains to be clarified.

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Inhibition of Human and Animal Platelet Adhesiveness to Glass Bead Columns by Adenosine, Dipyridamole, Chlorpromazine and Acetylsalicylic Acid

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648055 ◽

1976 ◽

Vol 36 (02) ◽

pp. 401-410 ◽

Cited By ~ 6

Author(s):

Buichi Fujttani ◽

Toshimichi Tsuboi ◽

Kazuko Takeno ◽

Kouichi Yoshida ◽

Masanao Shimizu

Keyword(s):

Guinea Pig ◽

Acetylsalicylic Acid ◽

Guinea Pigs ◽

Glass Bead ◽

Animal Species ◽

Inhibitory Effect ◽

Rabbit Platelet ◽

Platelet Adhesiveness

SummaryThe differences among human, rabbit and guinea-pig platelet adhesiveness as for inhibitions by adenosine, dipyridamole, chlorpromazine and acetylsalicylic acid are described, and the influence of measurement conditions on platelet adhesiveness is also reported. Platelet adhesiveness of human and animal species decreased with an increase of heparin concentrations and an increase of flow rate of blood passing through a glass bead column. Human and rabbit platelet adhesiveness was inhibited in vitro by adenosine, dipyridamole and chlorpromazine, but not by acetylsalicylic acid. On the other hand, guinea-pig platelet adhesiveness was inhibited by the four drugs including acetylsalicylic acid. In in vivo study, adenosine, dipyridamole and chlorpromazine inhibited platelet adhesiveness in rabbits and guinea-pigs. Acetylsalicylic acid showed the inhibitory effect in guinea-pigs, but not in rabbits.

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