Modified Vaccinia Virus Ankara

Volz, Asisa; Sutter, Gerd

doi:10.1016/bs.aivir.2016.07.001

Cited by 240 publications

(86 citation statements)

References 243 publications

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“…Thus, finding and developing effective, safe, stable, inexpensive, and easy-to-administer vaccines that can protect the global community against future epidemics are necessary (4). One of the most promising vaccine vectors is the poxvirus MVA, which has been used as a vaccine candidate against several infectious diseases (34)(35)(36). Here, we generated and characterized the immunogenicity and efficacy of novel MVA-based vaccine candidates against EBOV and SUDV (termed MVA-EBOV/SUDVs MVA-GP Zaire, MVA-GP Sudan, MVA-GP-2A-VP40 Zaire, MVA-GP-2A-VP40 Sudan, and MVA-GP-VP40 Zaire) expressing GP or GP together with VP40 of Zaire and Sudan ebolavirus species.…”

Section: Discussionmentioning

confidence: 99%

“…One of the most promising viral vectors is the highly attenuated poxvirus strain modified vaccinia virus Ankara (MVA), which was generated by passaging the Turkish smallpox vaccine chorioallantoic vaccinia virus Ankara (CVA) strain more than 570 times in primary chicken embryo fibroblast (CEF) cells (32). MVA has been widely used in several preclinical and clinical trials as a vaccine vector against multiple infectious diseases and cancer (33)(34)(35)(36), showing that MVA vectors are safe, express high levels of the heterologous antigens, and are strongly immunogenic. Thus, the use of MVA as a vector to generate a vaccine candidate against ebolavirus could be a useful approach to counteract the disease.…”

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confidence: 99%

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Distinct Immunogenicity and Efficacy of Poxvirus-Based Vaccine Candidates against Ebola Virus Expressing GP and VP40 Proteins

Lázaro-Frías

Gómez‐Medina

Sánchez-Sampedro

et al. 2018

J Virol

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and species cause a severe disease in humans and nonhuman primates (NHPs) characterized by a high mortality rate. There are no licensed therapies or vaccines against Ebola virus disease (EVD), and the recent 2013 to 2016 outbreak in West Africa highlighted the need for EVD-specific medical countermeasures. Here, we generated and characterized head-to-head the immunogenicity and efficacy of five vaccine candidates against Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV) based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing either the virus glycoprotein (GP) or GP together with the virus protein 40 (VP40) forming virus-like particles (VLPs). In a human monocytic cell line, the different MVA vectors (termed MVA-EBOVs and MVA-SUDVs) triggered robust innate immune responses, with production of beta interferon (IFN-β), proinflammatory cytokines, and chemokines. Additionally, several innate immune cells, such as dendritic cells, neutrophils, and natural killer cells, were differentially recruited in the peritoneal cavity of mice inoculated with MVA-EBOVs. After immunization of mice with a homologous prime/boost protocol (MVA/MVA), total IgG antibodies against GP or VP40 from Zaire and Sudan ebolavirus were differentially induced by these vectors, which were mainly of the IgG1 and IgG3 isotypes. Remarkably, an MVA-EBOV construct coexpressing GP and VP40 protected chimeric mice challenged with EBOV to a greater extent than a vector expressing GP alone. These results support the consideration of MVA-EBOVs and MVA-SUDVs expressing GP and VP40 and producing VLPs as best-in-class potential vaccine candidates against EBOV and SUDV. EBOV and SUDV cause a severe hemorrhagic fever affecting humans and NHPs. Since their discovery in 1976, they have caused several sporadic epidemics, with the recent outbreak in West Africa from 2013 to 2016 being the largest and most severe, with more than 11,000 deaths being reported. Although some vaccines are in advanced clinical phases, less expensive, safer, and more effective licensed vaccines are desirable. We generated and characterized head-to-head the immunogenicity and efficacy of five novel vaccines against EBOV and SUDV based on the poxvirus MVA expressing GP or GP and VP40. The expression of GP and VP40 leads to the formation of VLPs. These MVA-EBOV and MVA-SUDV recombinants triggered robust innate and humoral immune responses in mice. Furthermore, MVA-EBOV recombinants expressing GP and VP40 induced high protection against EBOV in a mouse challenge model. Thus, MVA expressing GP and VP40 and producing VLPs is a promising vaccine candidate against EBOV and SUDV.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Distinct Immunogenicity and Efficacy of Poxvirus-Based Vaccine Candidates against Ebola Virus Expressing GP and VP40 Proteins

Lázaro-Frías

Gómez‐Medina

Sánchez-Sampedro

et al. 2018

J Virol

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“…Thus, based on the positive findings that have been obtained with poxvirus-based vectors, such as the eradication of smallpox and the use of recombinant poxvirus vectors in several preclinical and clinical trials as candidate vaccines against a wide spectrum of pathologies [32][33][34], we reasoned that using a potent immunization protocol for T and B cell activation based on combined DNA as a priming component followed by poxvirus MVA vectors as booster [50], we could develop a useful vaccination strategy, which in turn could provide important insights on how best to direct a more effective vaccination against AD. Hence, in this study we have generated two novel MVA-based vaccine candidates against AD that express either the full-length Tau4R2N protein or the Tau3RC mutant protein, termed MVA-Tau4R2N and MVA-Tau3RC, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Modified vaccinia virus Ankara (MVA) is a highly attenuated poxvirus vector extensively used in several preclinical and clinical trials as a vaccine candidate against numerous infectious diseases and cancer [32][33][34]. MVA is safe, well tolerated and expresses high levels of heterologous antigens, triggering potent immune responses against them [35].…”

Section: Introductionmentioning

confidence: 99%

Tauopathy Analysis in P301S Mouse Model of Alzheimer Disease Immunized with DNA and MVA Poxvirus-Based Vaccines Expressing Human Full-Length 4R2N or 3RC Tau Proteins

et al. 2020

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Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive memory loss and cognitive decline that has been associated with an accumulation in the brain of intracellular neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein, and extracellular senile plaques formed by β-amyloid peptides. Currently, there is no cure for AD and after the failure of anti β-amyloid therapies, active and passive tau immunotherapeutic approaches have been developed in order to prevent, reduce or ideally reverse the disease. Vaccination is one of the most effective approaches to prevent diseases and poxviruses, particularly modified vaccinia virus Ankara (MVA), are one of the most promising viral vectors used as vaccines against several human diseases. Thus, we present here the generation and characterization of the first MVA vectors expressing human tau genes; the full-length 4R2N tau protein or a 3RC tau fragment containing 3 tubulin-binding motifs and the C-terminal region (termed MVA-Tau4R2N and MVA-Tau3RC, respectively). Both MVA-Tau recombinant viruses efficiently expressed the human tau 4R2N or 3RC proteins in cultured cells, being detected in the cytoplasm of infected cells and co-localized with tubulin. These MVA-Tau vaccines impacted the innate immune responses with a differential recruitment of innate immune cells to the peritoneal cavity of infected mice. However, no tau-specific T cell or humoral immune responses were detected in vaccinated mice. Immunization of transgenic P301S mice, a mouse model for tauopathies, with a DNA-Tau prime/MVA-Tau boost approach showed no significant differences in the hyperphosphorylation of tau, motor capacity and survival rate, when compared to non-vaccinated mice. These findings showed that a well-established and potent protocol of T and B cell activation based on DNA/MVA prime/boost regimens using DNA and MVA vectors expressing tau full-length 4R2N or 3RC proteins is not sufficient to trigger tau-specific T and B cell immune responses and to induce a protective effect against tauopathy in this P301S murine model. In the pursuit of AD vaccines, our results highlight the need for novel optimized tau immunogens and additional modes of presentation of tau protein to the immune system.

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“…This vaccine is shown to induce an antibody profile that is similar to that induced by the conventional first-generation vaccine and to protect various laboratory animals against zoonotic orthopoxviruses [71-73]. Imvanex/Imvamune has been licensed in European countries, Canada, and the United States.…”

Section: Modern Anti-smallpox Vaccinesmentioning

confidence: 99%

40 Years without Smallpox

Shchelkunova

Shchelkunov

2017

Acta Naturae

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The last case of natural smallpox was recorded in October, 1977. It took humanity almost 20 years to achieve that feat after the World Health Organization had approved the global smallpox eradication program. Vaccination against smallpox was abolished, and, during the past 40 years, the human population has managed to lose immunity not only to smallpox, but to other zoonotic orthopoxvirus infections as well. As a result, multiple outbreaks of orthopoxvirus infections in humans in several continents have been reported over the past decades. The threat of smallpox reemergence as a result of evolutionary transformations of these zoonotic orthopoxviruses exists. Modern techniques for the diagnostics, prevention, and therapy of smallpox and other orthopoxvirus infections are being developed today.

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Modified Vaccinia Virus Ankara

Cited by 240 publications

References 243 publications

Distinct Immunogenicity and Efficacy of Poxvirus-Based Vaccine Candidates against Ebola Virus Expressing GP and VP40 Proteins

Distinct Immunogenicity and Efficacy of Poxvirus-Based Vaccine Candidates against Ebola Virus Expressing GP and VP40 Proteins

Tauopathy Analysis in P301S Mouse Model of Alzheimer Disease Immunized with DNA and MVA Poxvirus-Based Vaccines Expressing Human Full-Length 4R2N or 3RC Tau Proteins

40 Years without Smallpox

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