Patent 11224647 - Safe potent single platform vaccine against Tier 1 select agents and other pathogens > Claims
1. An immunogenic composition comprising: a recombinant attenuated Francisella tularensis subspecies holarctica live vaccine Strain (LVS) having a deleted CapB gene (SEQ ID NO: 1) which comprises a F. tularensis promoter that expresses a fusion protein comprising an antigenic polypeptide epitope present in a Burkholderia pseudomallei polypeptide; wherein: the fusion protein expressed by the F. tularensis promoter is less than 80 kilodaltons in size; and the antigenic polypeptide epitope elicits an immune response in a mammalian host when the immunogenic composition is administered orally, intradermally (i.d.), subcutaneously (s.q.), intramuscularly (i.m.), or intranasally (i.n.) to the mammalian host. 2. The immunogenic composition of claim 1 , wherein the antigenic polypeptide epitope is present in a Burkholderia pseudomallei polypeptide selected from:Hcp-1 (SEQ ID NO: 35), Hcp-2 (SEQ ID NO: 36), Hcp-3 (SEQ ID NO: 37), Hcp-4 (SEQ ID NO: 38), Hcp-6 (SEQ ID NO: 39), LolC (SEQ ID NO: 40), TypA (SEQ ID NO: 41), BipB (SEQ ID NO: 42), BipC (SEQ ID NO: 43), BipD (SEQ ID NO: 44), Omp3 (SEQ ID NO: 45), Omp7 (SEQ ID NO: 46), Omp85 (SEQ ID NO: 47), OmpW (SEQ ID NO: 48), PotF (SEQ ID NO: 49), OppA (SEQ ID NO: 50), BopA (SEQ ID NO: 51), BimA (SEQ ID NO: 52), BPSL1897 (SEQ ID NO: 53), BPSL3369 (SEQ ID NO: 54), BPSL2287 (SEQ ID NO: 55), BPSL2765 (SEQ ID NO: 56), and VgrG5 (SEQ ID NO: 57). 3. The immunogenic composition of claim 1 , wherein the F. tularensis promoter comprises a bfr promoter (SEQ ID NO: 13) and/or an omp promoter (SEQ ID NO: 14).4. The immunogenic composition of claim 1 , wherein the LVS expresses two or more antigenic polypeptide epitopes present in a Burkholderia pseudomallei polypeptide.5. A method of generating an immune response in a mammal comprising administering the immunogenic composition of claim 1 to the mammal so that an immune response is generated to the antigenic polypeptide epitope present in a Burkholderia pseudomallei polypeptide.6. The method of claim 5 , wherein the method comprises administering the immunogenic composition ofclaim 1 in a primary vaccination; and administering the immunogenic composition ofclaim 1 in a subsequent homologous booster vaccination.8. The method of claim 6 , wherein the method comprises administering the immunogenic composition to the mammal less than 4 times.
7. The method of claim 5 , wherein the method consists essentially of administering the immunogenic composition ofclaim 1 in a primary vaccination; and administering the immunogenic composition ofclaim 1 in a subsequent homologous booster vaccination.9. The method of claim 5 , wherein the method comprises administering the composition ofclaim 1 in a primary vaccination; and administering a second heterologous immunogenic composition comprising the antigenic polypeptide epitope present in a Burkholderia pseudomallei polypeptide in a subsequent booster vaccination.10. The method of claim 9 , wherein the second immunogenic composition comprises an attenuated strain of Listeria monocytogenes expressing the antigenic polypeptide epitope.12. The method of claim 10 , wherein the method comprises administering the composition ofclaim 1 and the second immunogenic composition to the mammal less than a total of four times.13. The method of claim 12 wherein method comprises administering a single dose of the composition ofclaim 1 , and one or more doses of the second immunogenic composition.
11. The method of claim 1 , wherein the fusion protein is less than 50 kilodaltons.
14. An immunogenic composition comprising: a recombinant attenuated Francisella tularensis subspecies holarctica live vaccine Strain (LVS) having a deleted CapB gene (SEQ ID NO: 1) which comprises a F. tularensis promoter that expresses a fusion protein comprising an antigenic polypeptide epitope present in a Burkholderia pseudomallei polypeptide; wherein: the F. tularensis promoter comprises a bfr promoter (SEQ ID NO: 13); the antigenic polypeptide epitope is present in a Burkholderia pseudomallei Hep-6 (SEQ ID NO: 39) polypeptide; the fusion protein is less than 80 kilodaltons in size; and the antigenic polypeptide epitope elicits an immune response in a mammalian host when the immunogenic composition is administered orally, intradermally (i.d.), subcutaneously (s.q.), intramuscularly (i.m.), or intranasally (i.n.) to the mammalian host.