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Genotypes other than classical rabies virus in the genus Lyssavirus can cause disease similar to rabies through host switching from bat in to terrestrial animals. All vaccinal strains currently available developed from rabies virus and neutralize partially or may not neutralize rabies related viruses based on glycoprotein structure similarity. As an example, classical rabies based vaccine cannot protect from disease caused by African divergent genotypes; Mekola and Legos bat rabies related viruses. Thus, evaluation of locally produced vaccine with locally circulating viruses help to reduce possible protection failure and guarantee efficacy of the vaccine. This book also briefly describes techniques and methodology used to test pathogenicity and cross neutralization of Lyssavirus and helps to undertake different laboratory activities when dealing with Lyssavirus, specifically rabies virus.