Abstract: Provided herein are alphavirus vectors derived from South African Arbovirus No. 86 (S.A.AR86) comprising attenuating mutations and methods of making the same. Also provided are improved viral vectors and helper constructs comprising a S.A.AR86 capsid enhancer sequence. The present invention also provides S.A.AR86 replicon and helper constructs comprising an alphavirus capsid enhancer sequence. Further provided are methods of administering an alphavirus vector comprising a heterologous nucleotide sequence (preferably encoding an immunogen or a therapeutic polypeptide) according to the invention to a cell or subject. In preferred embodiments, the alphavirus vector delivers the heterologous nucleotide sequence to the cells of the bone, bone marrow, and/or bone-associated connective tissue.

Abstract: Provided herein are alphavirus vectors derived from South African Arbovirus No. 86 (S.A.AR86) comprising attenuating mutations and methods of making the same. Also provided are improved viral vectors and helper constructs comprising a S.A.AR86 capsid enhancer sequence. The present invention also provides S.A.AR86 replicon and helper constructs comprising an alphavirus capsid enhancer sequence. Further provided are methods of administering an alphavirus vector comprising a heterologous nucleotide sequence (preferably encoding an immunogen or a therapeutic polypeptide) according to the invention to a cell or subject. In preferred embodiments, the alphavirus vector delivers the heterologous nucleotide sequence to the cells of the bone, bone marrow, and/or bone-associated connective tissue.