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We have used vaccinia-measles recombinant viruses to study vaccination in the presence of pre-existing antibody. When mice were vaccinated with recombinants expressing either the haemagglutinin (H) or fusion (F) measles virus (MV) proteins, the humoral response to the MV protein was suppressed by passively administered polyclonal antibody. However, individual monoclonal antibodies (H or F) did not...
Three vaccinia virus strains (Praha, DD--a DRYVAX Wyeth vaccine-derived virus--and LIVP) were examined for growth in various cell cultures and for virulence and immunogenicity in mice. The viruses did not differ by their growth rates in monkey kidney cells (CV-1), human diploid cells (LEP), rat TK - cells (RAT2) or primary dog kidney cells. The immunogenicity of Praha and DD viruses was...
The highly attenuated, replication-deficient, modified vaccinia virus Ankara (MVA) was used to express the fusion (F) and/or hemagglutinin-neuraminidase (HN) glycoproteins of parainfluenza virus 3 (PIV3). Initial recombinant viruses in which the HN gene was regulated by a very strong synthetic early/late promoter replicated poorly in permissive chick embryo cells evidently due to toxic levels of...
The presence and consistent expression of the genes encoding the human papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours presents the opportunity for an immunotherapeutic approach for control of the disease. This report describes the construction and characterisation of a recombinant vaccinia virus designed to express modified forms of the E6 and E7 proteins from HPV16...
Recombinant vaccinia virus (VV) vectors that express the envelope (Env) protein of the human immunodefiency virus-type 1 (HIV-1) have been previously shown to elicit HIV-specific cytotoxic T-lymphocyte (CTL) and weak antibody responses in non-human primate studies and clinical trials. In first clinical trials, single Env proteins were presented to the immune system by VV recombinants and other vectors,...
Modified vaccinia virus Ankara (MVA), a highly attenuated strain of vaccinia virus (VV) that is unable to replicate in most mammalian cells, was evaluated as an expression vector for a model tumor associated antigen (TAA) and as a potential anti-cancer vaccine. We employed an experimental murine model in which an adenocarcinoma tumor line, CT26.CL25, was stably transfected with a model TAA, β-galactosidase...
Recombinant vaccinia viruses containing tumor associated genes represent an attractive vector to induce immune responses to weak immunogens in cancer immunotherapy protocols. The property of intense immunogenicity of vaccinia proteins, however, also serves to limit the number of inoculations of recombinant vaccinia viruses. Host immune responses to the first immunization have been shown to limit...
Genes encoding four different C-terminal fragments of a Plasmodium falciparum merozoite surface antigen were generated: MSA1C-(Si,A), containing signal and anchor regions of MSA1; MSA1C-(Si,nA), containing the signal but not the anchor; MSA1C-(nSi,A), containing the anchor but not the signal, and MSA1C-(nSi,nA) containing neither the signal nor the anchor region. Each gene was inserted into the thymidine...
The efficiency of paraformaldehyde (PFA) and binary ethylenimine (BEI) in inactivating recombinant vaccinia virus (rVV), present in baby hamster kidney cells expressing simian immunodeficiency virus envelope glycoproteins (SIV-Env), was measured in a series of inactivation studies. Both compounds were shown to be effective in reducing rVV titres. The use of standard 3-day titration assays proved...
Administration of vaccinia immune globulin (VIG), derived from vaccinated healthy adult volunteers, is the treatment-of-choice for patients suffering from severe complications following smallpox vaccination. The present study was aimed to determine the time interval after vaccination, at which the highest titer of neutralizing antibodies is obtained. Ninety-nine 18-year-old soldiers, immunized with...
Genes encoding the glycosylated precursor of the membrane (prM) and envelope (E) proteins of a Korean strain of Japanese encephalitis virus (JEV) were inserted into the genome of the host-range restricted, highly attenuated, and safety-tested MVA strain of vaccinia virus. MVA recombinants containing the JEV genes, under strong synthetic or modified H5 vaccinia virus promoters, were isolated. Synthesis...
Type 1 and type 2 immune responses are modulated by IL12 or IL4, respectively, at the time of lymphocyte priming. Importantly, type 1 responses have been associated with resistance to retroviral infection in mice, humans, and ruminants. Specifically, vaccination of sheep with vaccinia virus expressing bovine leukemia virus (BLV) gp51 resulted in protective immunity with the characteristics of a type...
The immune responses elicited after oral delivery of vaccinia virus (VV) recombinants are not well defined. In this study we show with mice, that after oral administration of a VV recombinant expressing the luciferase reporter gene, VV gene expression takes place for several days in gut-associated lymphoid (GALT) tissues as well as in the spleen. After 14 days, a significant mucosal IgA response against...
Recombinant DNA and vaccinia virus (VV) vectors that express envelope (Env) proteins of the human immunodeficiency virus (HIV) have each been prominently utilized in vaccine development. These two vectors (termed DNA-Env and VV-Env) are attractive vaccine candidates due to their abilities to elicit both cytotoxic T-lymphocyte and B-cell responses. Our previous work demonstrated that DNA-Env primed...
Intranasal and intramuscular immunizations of mice with the highly attenuated MVA strain of vaccinia virus expressing the respiratory syncytial virus (RSV) F or G glycoprotein induced higher RSV antibody titers than those achieved by infection with RSV and greatly restricted the replication of RS challenge virus in both the upper and lower respiratory tracts. In addition, a recombinant MVA expressing...
The nonreplicating chicken adapted vaccinia virus strain MVA was used in a combined vaccine scheme. Using the equine herpesvirus type 1 (EHV-1) encoded complement-receptor glycoprotein C as antigen, only poor antibody response was induced by exclusive vaccination with DNA plasmids. The administration of recombinant MVA followed by plasmid immunization elicited both humoral and cellular immune responses...
A vaccine based on the envelope protein (Env) of the human immunodeficiency virus type 1 (HIV-1) that triggers widely reactive antibodies might be a desirable approach to control virus infection. To expose epitopes which could induce broadly reactive antibodies against HIV-1 Env, we have generated vaccinia virus (VV) recombinants that express Env fused at its N- or C-terminus with two major antigenic...
The immunogenicity of recombinant modified vaccinia Ankara, a highly attenuated vaccinia virus, expressing influenza nucleoprotein (MVA-NP) and HIV-1 gag (MVA-gag) was investigated. Restimulation of peripheral blood lymphocytes of healthy subjects with MVA-NP led to expansion of CTL with specificity for known NP epitopes. These CTL efficiently lysed NP peptide-pulsed targets and released interferon-γ...
The recombinant vaccinia viruses expressing the surface protein of Neospora caninum tachyzoite, NcSAG1 or NcSRS2, were constructed. The vaccination with these recombinant viruses could protect effectively the parasite invasion in a mouse model system. The vaccine efficacy of NcSRS2 was higher than that of NcSAG1. The present study indicated that a high level of IgG1 Ab production to parasite is important...
Neospora caninum infection is the major cause of bovine abortion. To develop a vaccine against N. caninum infection, recombinant vaccinia viruses carrying NcSRS2 and NcSAG1 genes (vv/Nc-p43 and vv/Nc-p36, respectively) were constructed and were tested in a mouse model. Vaccination of dams with vv/Nc-p43 appeared to confer effective protection against vertical transmission to offspring, though that...
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