Infectious RNA vaccine protects mice against chikungunya virus infection.

Infectious RNA vaccine protects mice against chikungunya virus infection.

Publication date: Dec 03, 2020

We describe a novel vaccine platform that can generate protective immunity to chikungunya virus (CHIKV) in C57BL/6J mice after a single immunization by employing an infectious RNA (iRNA), which upon introduction into a host cell launches an infectious attenuated virus. We and others have previously reported that an engineered deletion of 183 nucleotides in the nsP3 gene attenuates chikungunya virus (CHIKV) and reduces in vivo viral replication and viremia after challenge in mice, macaques and man. Here, we demonstrated that in vitro transfection of iRNA carrying the nsP3 deletion generated infectious viruses, and after intramuscular injection, the iRNA induced robust antibody responses in mice. The iRNA was superior at eliciting binding and neutralizing antibody responses as compared to a DNA vaccine encoding the same RNA (iDNA) or a non-propagating RNA replicon (RREP) lacking the capsid encoding gene. Subsequent challenge with a high dose of CHIKV demonstrated that the antibody responses induced by this vaccine candidate protected animals from viremia. The iRNA approach constitutes a novel vaccine platform with the potential to impact the spread of CHIKV. Moreover, we believe that this approach is likely applicable also to other positive-strand viruses.

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Concepts Keywords
Antibody Vaccination
Attenuated Virus Virology
Capsid Clinical medicine
Chikungunya Medicine
Gene Medical specialties
IDNA Immunization
Immunity Infectious vaccine
Immunization Chikungunya virus infection
Infection Viral replication viremia
Intramuscular Injection Chikungunya
IRNA Attenuated vaccine
Mice Virus
Nucleotides
Sci
Transfection
Vaccine
Viral Replication
Viremia
Virus
Viruses
Vivo

Semantics

Type Source Name
disease MESH chikungunya virus infection
disease MESH viremia
drug DRUGBANK Coenzyme M
disease MESH polyarthritis
disease MESH encephalitis
disease MESH infection
disease MESH infectious diseases
drug DRUGBANK Amino acids
disease MESH growth
disease MESH Tumor
pathway REACTOME Budding
drug DRUGBANK Water
drug DRUGBANK Phosphate ion
drug DRUGBANK Methylergometrine
drug DRUGBANK Human Serum Albumin
drug DRUGBANK Carboxymethylcellulose
drug DRUGBANK Benzylpenicillin
drug DRUGBANK Streptomycin
drug DRUGBANK L-Glutamine
drug DRUGBANK Gentian violet cation
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH yellow fever
disease MESH measles
pathway KEGG Measles
disease MESH mumps
disease MESH rubella
drug DRUGBANK Huperzine B
drug DRUGBANK Spinosad
disease MESH Military
disease MESH Venezuelan equine encephalitis
drug DRUGBANK Yellow Fever Vaccine
disease MESH zika virus infection
disease MESH influenza
disease MESH atherogenesis
disease MESH rabies

Original Article

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