Evaluation of the protective efficacy of a rabies DNA vaccine in mice using an intracerebral challenge model

Abstract

An eultaryotic expression plasmid expressing therabies virus surface glycoprotein (G-protein) under the control of cytomegalovirus inmediate early promoter and iniron was constructed. This plasnlid designated as pCMYRab also contains the gene conferring resistance to kanarnycin (kanR) to bacteria harbouring this plasmid rather than that conferring resistance to ampicillin (ampR) and thus is devoid of the CpG immunostimuliatory sequences (ISS) present in the latter. Thc ability of pCMVRab to induce Protective immune response was examined in outbred swiss mics using an inlracerebral (i.e.) rabies virus challenge model. Following intramuscular (i.m.) innoculation, anti-G protein aniibodies as well as virus neutralizing antibodies (YNA) are detected in the sera of immunized mice up to four months after immunization. Rabies virus-specific T helper cell proliferation roufci be demonstrated up to six months after immunization Induction of these immune responses in pCMVRab- immmnized mice results in significant protection against a subsequent lethal i.c. rabies virus challenge. Thus, we demonstrate for the first time that a rabies G protein expression plasmid devoid of the JSS present in the nmpR gene confers significant protection against i.e. rabies virus challenge when inocnfated into the skeletal muscle of outbred swiss mice.