Immunization with Toscana virus N-Gc proteins protects mice against virus challenge.
Toscana virus (TOSV) is an emerging virus, circulating in the Mediterranean area, that is responsible for aseptic meningitis, meningoencephalitis, and encephalitis. The development of a vaccine that could provide complete protection from TOSV infection is needed. In this study we investigated the capacity of TOSV structural proteins, nucleocapsid protein N and the two Gc and Gn glycoproteins, produced as recombinant proteins, in an animal model. In particular, we investigated their role in inducing specific and protective immune responses against virus infection. Mice were immunized intraperitoneally using TOSV antigens singly or in combination. The results show that only the N-Gc combination was able to protect 100% of animals from a lethal challenge with a neurovirulent strain of TOSV. This potential vaccine induces high serum antibody titres with neutralizing activity and it is safe for animals. Moreover, immunization induces a virus specific cell-mediated immune response, in particular a CD8+ T cell response associated with a marked expression of interferon gamma. These results indicate that the N+Gc viral antigen combination could be useful for future development of a vaccine controlling the spread of this emerging virus that could pose a new threat for humans.
Gori Savellini
Gianni
G
Department of Molecular Biology, Section of Microbiology, University of Siena, Siena, Italy.
Di Genova
Giuseppa
G
Terrosi
Chiara
C
Di Bonito
Paola
P
Giorgi
Colomba
C
Valentini
Melissa
M
Docquier
Jean-Denis
JD
Cusi
Maria Grazia
MG
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D019590:Nucleocapsid Proteins / Q000276:immunology*; D010217:Phlebotomus Fever / Q000276:immunology* / Q000517:prevention & control*; D029301:Sandfly fever Naples virus / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage
D000914:Antibodies, Viral; D019590:Nucleocapsid Proteins; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; D007371:Interferon-gamma