THE IMMUNOGENIC AND PATHOGENIC POTENTIAL OF SHORT POLY(C) TRACT MENGOVIRUSES

We have shown previously that genetically engineered Mengo viruses wit h artificial deletions in their 5' noncoding polyribocytidylic acid (p oly(C)) tracts are highly attenuated for the natural murine host and a lso for other animals such as baboons, macaques, and domestic pigs. Th e present report further characterizes select short poly(C) tract Mang o viruses in the natural murine host. A positive correlation was found between the length of the poly(C) tract and murine virulence, as meas ured by virus brain titers and brain lesion scores after infection. Hi stological examination of brain tissue collected from infected animals clearly showed that the short poly(C) tract viruses did not induce th e devastating pathological effects characteristic of animals inoculate d with wild-type virus. Instead, the short-tract Mango viruses proved excellent immunological agents. A dose of only 100 plaque-forming unit s of VMC(24) (poly(C) tract: C13UC10), injected subcutaneously, protec ted 80% of recipient animals against a normally lethal dose of encepha lomyocarditis virus. The protection was long-lived, and animals simila rly immunized with vMC(0) virus (poly(C) tract: C-0) still had protect ive neutralizing antibody titers up to 16 months after inoculation. In addition, the short-tract Viruses proved genetically stable, in that the vMC(24) virus did not yield detectable pathogenic revertants even after multiple, forced passages in 4-week-old mice. These studies sugg est that Mengo viruses containing deletions in their poly(C) tracts ar e biologically safe and potent immunogens and imply that they may have uses as cardiovirus vaccines. (C) 1996 Academic Press, Inc.