Compositions and Administration of Chimeric Glycoprotein Lyssavirus Vaccines for Coverage Against Rabies

Abstract

The present disclosure is directed towards chimeric glycoproteins wherein the clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain are defined by starting from the amino terminus of the protein, these domains are comprised of the following amino acid residue ranges: clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain; and wherein the clip, core, flap, transmembrane, and cytoplasmic domain comprise a chimeric combination of at least two lyssavirus, wherein the chimeric glycoprotein is advantageously inserted into a rabies-based vaccine vector.

1 - 31 . (canceled) 
     
     
         32 . A chimeric lyssavirus glycoprotein comprising components of at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoproteins within a clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain, wherein the clip region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; wherein the core region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLY, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; wherein the flap region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; and wherein the transmembrane and cytoplasmic domain are from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein. 
     
     
         33 . The chimeric glycoprotein of  claim 32  wherein the glycoprotein is inserted into a rabies virus vector between the nucleoprotein and the phosphoprotein. 
     
     
         34 . The chimeric glycoprotein of  claim 33  wherein the glycoprotein inserted into the a rabies vector is inactivated and provided in an immunogenic composition. 
     
     
         35 . The chimeric glycoprotein of  claim 32  wherein the clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain are defined by starting from the amino terminus of the protein, these domains are comprised of the following amino acid residue ranges:clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain. 
     
     
         36 . A method of eliciting an immunogenic response to lyssaviruses comprising intramuscular administration of an immunogenic composition containing inactivated chimeric glycoprotein viruses, wherein said inactivated chimeric glycoprotein viruses comprise components of at least one of RABV, ARAV, BBLV, EBLV-2 ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoproteins within a clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain, wherein the clip region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; wherein the core region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; wherein the flap region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; and wherein the transmembrane and cytoplasmic domain are from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein. 
     
     
         37 . The method of  claim 36  wherein the immunogenic composition is administered as at least 3 doses over 4 weeks. 
     
     
         38 . The method of  claim 36  wherein the immunogenic composition is administered as at least 4 doses over 4 weeks. 
     
     
         39 . The method of  claim 36 , wherein the clip region, core region, flap region, transmembrane, and cytoplasmic domain are defined by starting from the amino terminus of the protein, and are comprised of the following amino acid residue ranges: clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain. 
     
     
         40 . A nucleic acid encoding a chimeric G, comprising a clip region, core region, flap region, and a transmembrane and cytoplasmic domain of at least two different lyssaviruses, administered to a patient in its nucleic acid form, wherein the clip region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; wherein the core region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; wherein the flap region is from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein; and wherein the transmembrane and cytoplasmic domains are from at least one of RABV, ARAV, KHUV, BBLV, EBLV-2, ABLV, IRKV, EBLV-1, DUVV, MOKV, SHIBV, LBV, WCBV, IKOV, and LLEBV glycoprotein. 
     
     
         41 . A rabies viral vector comprising the nucleic acid of  claim 40 .