Infectious RNA vaccine protects mice against chikungunya virus infection

• Published in: Scientific reports 2020-12, Vol.10 (1), p.21076-21076, Article 21076
• Main Authors: Szurgot, Inga, Ljungberg, Karl, Kümmerer, Beate M., Liljeström, Peter
• Format: Article
• Language: English
• Subjects: 631/250/590/2293; 631/326/596/1282; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Chikungunya Fever - immunology; Chikungunya Fever - prevention & control; Chikungunya Fever - virology; Chikungunya virus; Chikungunya virus - genetics; Chikungunya virus - immunology; Chikungunya virus - pathogenicity; DNA vaccines; Female; Gene deletion; Humanities and Social Sciences; Immunization; Immunogenicity, Vaccine; Injections, Intramuscular; Mice; Mice, Inbred C57BL; mRNA Vaccines; multidisciplinary; Mutation; Nucleotides; Protected animals; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Transfection; Vaccines; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vector-borne diseases; Viral Nonstructural Proteins - genetics; Viral Nonstructural Proteins - immunology; Viremia; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-78009-7

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.