Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus

Roques, Pierre; Ljungberg, Karl; Kümmerer, Beate M.; Gosse, Laurent; Dereuddre‐Bosquet, Nathalie; Tchitchek, Nicolas; Holzmann, David; García-Arriaza, Juan; Meinke, Andreas; Esteban, Mariano; Merits, Andres; Grand, Roger Le; Liljeström, Peter

doi:10.1172/jci.insight.83527

Cited by 76 publications

(74 citation statements)

References 60 publications

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“…All these genes were inserted in the vector backbone of an optimized parental MVA, which also contained deletions in the vaccinia virus (VACV) immunomodulatory genes C6L, K7R, and A46R (termed MVA-GFP) (see Materials and Methods). We have previously described that an MVA vector lacking those VACV genes and expressing chikungunya virus genes encoding the structural virus proteins is able to fully protect mice and NHPs after challenge with chikungunya virus (38,39).…”

Section: Resultsmentioning

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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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: Resultsmentioning

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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“…The other was a recombinant modified vaccinia virus that encoded the full CHIKV C-E3-E2-6K-E1. Both vaccine candidates showed similar results as 5nsP3, indicating good prospects for the future application of LAV (Roques et al, 2017).…”

Section: Lavmentioning

confidence: 68%

Recent Progress in Vaccine Development Against Chikungunya Virus

2019

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Chikungunya fever (CHIKF) is an acute infectious disease that is mediated by the mosquito-transmitted chikungunya virus (CHIKV). People infected with CHIKV may experience high fever, severe joint pain, skin rash, and headache. In recent years, this disease has become a global public health problem. However, there is no licensed vaccine available for CHIKV. Accumulating research data have provided novel approaches and new directions for the development of CHIKV vaccines. Our review focuses on recent progress in CHIKV vaccine studies. The potential vaccine candidates are classified into seven types: inactivated vaccine, subunit vaccine, liveattenuated vaccine, recombinant virus-vectored vaccine, virus-like particle vaccine, chimeric vaccine, and nucleic acid vaccine. These studies will provide important insights into the future development of CHIKV vaccines.

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“…An attenuated sequence of CHIKV (Δ5nsP3), a DNA-launched RNA replicon with encoding of CHIKV envelope proteins (DREP-E) and a DREP-E prime with modified Ankara encoding CHIKV capsid showed protection against a wild type Chikungunya virus. These vaccinations developed both humoral and cellular immunity and proved to be safe without showing any clinical signs [49]. Virus-like particles (VLP) containing the CHIKV envelope and capsid in their surface, as well as recombinant Measles virus with CHIKV polypeptides were able to replicate inside the host cells.…”

Section: Prevention and Controlmentioning

confidence: 99%

Origins, pathophysiology, diagnosis, vaccination and prevention of Chikungunya virus

Rafe

Ahmed

2019

Current Issues in Pharmacy and Medical Sciences

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Chikungunya virus is an Alphavirus that possesses characteristics similar to that of an arthropod-borne virus. Chikungunya virus has been one of the major concerns for the last few decades due to its nature of explosive spreading throughout the world. This article is intended to give detailed information about Chikungunya virus, and includes its pathogenesis, origins, diagnosis, treatment and prevention. Although, recent researches suggests various approaches to treating Chikungunya virus, extensive literature search on Chikungunya virus has revealed that, currently, there is no effective treatment available and the virus is greatly dependent on its vectors. Patients affected by Chikungunya virus mainly show symptoms of fever, arthralgia, joint pain and skin rash. Since there is no effective treatment available, public awareness is the most significant factor for potential prevention against Chikungunya virus.

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Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus

Cited by 76 publications

References 60 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

Recent Progress in Vaccine Development Against Chikungunya Virus

Origins, pathophysiology, diagnosis, vaccination and prevention of Chikungunya virus

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