Background:　Enterovirus　71　(EV71)　is　major　cause　of　hand,　foot　and　mouth　disease.　Large　epidemics　of　EV71　infection　have　been　recently　reported　in　the　Asian-Pacific　region.　Currently,　no　vaccine　is　available　to　prevent　EV71　infection.　Results:　The　peptide　(VP4N20)　consisting　of　the　first　20　amino　acids　at　the　N-terminal　of　VP4　of　EV71　genotype　C4　were　fused　to　hepatitis　B　core　(HBcAg)　protein.　Expression　of　fusion　proteins　in　E.　coli　resulted　in　the　formation　of　chimeric　virus-like　particles　(VLPs).　Mice　immunized　with　the　chimeric　VLPs　elicited　anti-VP4N20　antibody　response.　In　vitro　microneutralization　experiments　showed　that　anti-chimeric　VLPs　sera　were　able　to　neutralize　not　only　EV71　of　genotype　C4　but　also　EV71　of　genotype　A.　Neonatal　mice　model　confirmed　the　neutralizing　ability　of　anti-chimeric　VLPs　sera.　Eiptope　mapping　led　to　the　identification　of　a　＂core　sequence＂　responsible　for　antibody　recognition　within　the　peptide.　Conclusions:　Immunization　of　chimeric　VLPs　is　able　to　elicit　antibodies　displaying　a　broad　neutralizing　activity　against　different　genotypes　of　EV71　in　vitro.　The　＂core　sequence＂　of　EV71-VP4　is　highly　conserved　across　EV71　genotypes.　The　chimeric　VLPs　have　a　great　potential　to　be　a　novel　vaccine　candidate　with　a　broad　cross-protection　against　different　EV71　genotypes.