Generation and analysis of an RNA vaccine that protects against coxsackievirus B3 challenge.
Coxsackievirus B3 (CVB3) is an important human pathogen that causes substantial morbidity and mortality but, to date, no vaccine is available. We have generated an RNA-based vaccine against CVB3 and have evaluated it in the murine model of infection. The vaccine was designed to allow production of the viral polyprotein, which should be cleaved to generate most of the viral proteins in their mature form; but infectious virus should not be produced. In vitro translation studies indicated that the mutant polyprotein was efficiently translated and was processed as expected. The mutant RNA was not amplified in transfected cells, and infectious particles were not produced. Furthermore, the candidate RNA vaccine appeared safe in vivo, causing no detectable pathology following injection. Finally, despite failing to induce detectable neutralizing antibodies, the candidate RNA vaccine conferred substantial protection against virus challenge, either with an attenuated recombinant CVB3, or with the highly pathogenic wt virus.
Hunziker
Isabelle P
IP
Department of Neuropharmacology, CVN-9, The Scripps Research Institute, La Jolla, CA 92037, USA.
Harkins
Stephanie
S
Feuer
Ralph
R
Cornell
Christopher T
CT
Whitton
J Lindsay
JL
D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000235:genetics / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic; D014614:Vaccines, Synthetic / Q000276:immunology*; D014765:Viral Vaccines
D012367:RNA, Viral; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; C498008:pH3IH1 RNA vaccine