Rabbit Hemorrhagic Disease Virus (RHDV) is still considered highly contagious and fatal disease in Egypt although vaccination strategies. Until now there is no full detailed study concerning the antigenic
evolution of RHDV in the Egyptian field. The circulating RHDV isolates in the different Egyptian
governorates showed the existence of HA negative and positive as well as variable HA isolates without identification of these isolates on the molecular level. Sequence and phylogenetic analysis of the variable
region (C-E) of VP60 gene for seven local isolates revealed the presence of both original (Giza97&Kal2011) RHDV as well as variant (KS2000, Kal2000, Kal2005, Giza2010 and Kal2012) are
circulating in the Egyptian field till recent period with predominance of RHDVa subtype regardless to
special period or location without evidence of replacement of RHDVa the original RHDV. Original RHDV
strains showed completely different protean analysis from RHDVa strains as ten significant aa substitutions at region E amino acid have resulted in obvious changes in the antigenic index. Even
Giza2006 vaccine strain showed unique amino acid substitutions from other Egyptian variant strains. In
conclusion, the bioinformatics analysis may explain emergence of RHDV outbreaks although vaccination
programs using locally isolated Giza2006 variant strain thatrequire to revise the vaccination strategies and
extensive molecular epidemiological studies