Immunological compositions containing attenuated
This disclosure provides attenuated Histophilus somni strains, compositions comprising same, and methods of production and use thereof. The attenuated strains may express lower or no levels of various virulence-associated genes, relative to the corresponding pathogenic bacteria Advantageously, the attenuated Histophilus somni strains may be administered orally, intranasally, intra-tracheally, or subcutaneously.
1. A genetically engineered, non-naturally-occurring, attenuated Histophilus somni ( H. somni ), strain, wherein the attenuated strain has deletion of the genes HSM_0077, HSM_0270, HSM_0708, HSM_0975, HSM_1191, HSM_1257, HSM_1448, HSM_1542, HSM_1571, HSM_1624, HSM_1714, HSM_1726, HSM_1728, HSM_1730, HSM_1734, HSM_1736, HSM_1737, HSM_1741 and HSM_1793 to eliminate the ability of the genes to express their cognate wild type gene products, relative to a reference virulent H. somni strain, and wherein the attenuated strain possesses in its genome the genes HSM_0052, HSM_0164, HSM_0268, HSM_274, HSM_0338, HSM_0346, HSM_0377, HSM_0394, HSM_0598, HSM_0695, HSM_0749, HSM_0844, HSM_0938, HSM_0977, HSM_0978, HSM_1022, HSM_1089, HSM_1090, HSM_1160, HSM_1212, HSM_1426, HSM_1484, HSM_1616, HSM_1647, HSM_1651, HSM_1667, HSM_1794, and HSM_1889 relative to the reference virulent H. somni strain.
2. A vaccine composition comprising a pharmaceutically acceptable vehicle, diluent or excipient and an amount of the attenuated H. somni strain of claim 1 effective to elicit a protective immune response against a virulent strain of H. somni in a bovine animal.
3. The vaccine of claim 2 , wherein the vaccine is in the form of a formulation for intranasal or parenteral administration.
4. The vaccine of claim 2 , wherein the reference virulent strain comprises a genomic DNA sequence, which encodes and expresses 100% of the same genes as does a strain of H. somni having the sequence set forth in SEQ ID NO: 2.
5. The vaccine of claim 2 , wherein the attenuated H. somni strain encodes and expresses at least 99% of the same genes as does an attenuated H. somni strain having in its genome the sequence of SEQ ID NO: 4.
6. The vaccine of claim 2 , wherein the attenuated H. somni strain encodes and expresses 100% of the same genes as does an attenuated H. somni strain having in its genome the sequence of SEQ ID NO: 4.
7. The vaccine of claim 2 , wherein the attenuated H. somni strain encodes and expresses at least 99% of the same genes as does the attenuated H. somni strain deposited under the designation PTA-121030.
8. The vaccine of claim 2 , wherein the attenuated H. somni strain encodes and expresses 100% of the same genes as does the attenuated H. somni strain deposited under the designation PTA-121030.
9. The vaccine of claim 8 , wherein the composition is non-adjuvanted.
10. The vaccine of claim 8 , wherein the composition further comprises at least one additional antigen capable of eliciting a pathogen-specific immune response in a bovine animal.
11. The vaccine of claim 10 , wherein the at least one additional antigen is capable of eliciting the immune response in the bovine animal against bovine respiratory disease complex (BRDC), bovine respiratory syncytial virus (BRSV), bovine viral diarrhea (BVD), bovine parainfluenza 3 (P13), infectious bovine rhinotracheitis (IBR), bovine herpesvirus-1 (BHV-1), or bluetongue disease virus (BTV).
12. A method of eliciting a protective immune response in a bovine animal in need thereof against a subsequent virulent H. somni infection comprising the step of administering to the bovine animal an effective amount of the vaccine of claim 2 .
13. The method of claim 12 , wherein the administering is by intranasal, subcutaneous, or intramuscular route.