Compositions and methods of enhancing immune responses
AssigneesBoard of Trustees of the University of Arkansas, The Texas A&M University System
InventorsWalter Bottje, Billy Hargis, Luc Berghman, Young Min Kwon, Kimberly Cole, Mandy Cox, Sherryll Layton
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Abstract
Provided herein are Salmonella enteritidis 13A strains and compositions comprising these strains. Also provided are methods of enhancing an immune response against Influenza A and methods of reducing morbidity associated with an Influenza A infection. Methods of enhancing an immune response to a vaccine vector by expressing a polypeptide of CD 154 capable of binding CD40 are also disclosed. Methods of developing a bacterial vaccine vector are disclosed. Methods of generating scarless site-specific mutations in a bacterium are also disclosed.
Claims27
A vaccine vector comprising a polynucleotide sequence encoding an antigenic polypeptide and a CD154 polynucleotide sequence encoding a CD154 polypeptide capable of binding CD40, wherein the CD154 polypeptide has fewer than about 50 amino acids and comprises amino acids 140-149 of SEQ ID NO:26 or a homolog thereof, wherein the antigenic polypeptide is an Influenza polypeptide and wherein the polynucleotide sequence encoding the antigenic polypeptide and the CD154 polynucleotide sequence are expressed on the surface of the vaccine vector.
A method of enhancing an immune response against Influenza in a subject comprising administering to the subject a vaccine vector in an amount effective to enhance the immune response of the subject to Influenza in response to vaccination, the vaccine vector comprising a CD154 polynucleotide sequence encoding a CD154 polypeptide capable of binding CD40 and a polynucleotide sequence encoding an Influenza polypeptide, wherein the CD154 polypeptide has fewer than about 50 amino acids and comprises amino acids 140-149 of SEQ ID NO:26 or a homolog thereof and wherein the CD154 polypeptide is expressed on the surface of the vaccine vector.
A method of enhancing the immune response against Influenza A in a subject comprising administering to the subject a bacterium comprising at least one Influenza A M2e polynucleotide sequence encoding an Influenza A M2e polypeptide in an amount effective to enhance the immune response of the subject to Influenza A and a CD154 polynucleotide sequence encoding a CD154 polypeptide capable of binding CD40, wherein the CD154 polypeptide has fewer than about 50 amino acids and comprises amino acids 140-149 of SEQ ID NO:26 or a homolog thereof and wherein the CD154 polypeptide is expressed on the surface of the bacterium.
A method of reducing influenza A-related morbidity in a subject comprising administering to the subject a bacterium comprising at least one Influenza A M2e polynucleotide sequence encoding an Influenza A M2e polypeptide in an amount effective to reduce Influenza A related morbidity and a CD154 polynucleotide sequence encoding a CD154 polypeptide capable of binding CD40, wherein the CD154 polypeptide has fewer than about 50 amino acids and comprises amino acids 140-149 of SEQ ID NO:26 or a homolog thereof and wherein the CD154 polypeptide is expressed on the surface of the bacterium.
A method for developing a bacterial vaccine vector comprising:
- a) selecting a bacterium capable of colonizing a subject;
- b) attenuating the bacterium to generate an attenuated bacterium;
- c) incorporating a CD154 polynucleotide sequence encoding a CD154 polypeptide capable of binding CD40 into the attenuated bacterium to generate a vaccine vector, wherein the CD154 polypeptide has fewer than 50 amino acids and comprises amino acids 140-149 of CD154 SEQ ID NO:26 or a homolog thereof, and
- d) incorporating a second polynucleotide sequence encoding an antigenic polypeptide into the chromosome of the vaccine vector, wherein the CD154 polypeptide and the antigenic polypeptide are expressed on the surface of the vaccine vector.
Dependencies are inferred from the claim text.