Majarian, William R.; Stocker, Bruce A. D.; Newton, Salete M. C.;

Recombinant flagellin vaccines

The present invention is directed to recombinant genes and their encoded proteins which are recombinant flagellin fusion proteins. Such fusion proteins comprise amino acid sequences specifying an epitope encoded by a flagellin structural gene and an epitope of a heterologous organism which is immunogenic upon introduction of the fusion protein into a vertebrate host. The recombinant genes and proteins of the present invention can be used in vaccine formulations, to provide protection against infection by the heterologous organism, or to provide protection against conditions or disorders caused by an antigen of the organism. In a specific embodiment, attenuated invasive bacteria expressing the recombinant flagellin genes of the invention can be used in live vaccine formulations. The invention is illustrated by way of examples in which epitopes of malaria circumsporozoite antigens, the B subunit of Cholera toxin, surface and presurface antigens of Hepatitis B. VP7 polypeptide of rotavirus, envelope glycoprotein of HIV, and M protein of Streptococcus, are expressed in recombinant flagellin fusion proteins which assemble into functional flagella, and which provoke an immune response directed against the heterologous epitope, in a vertebrate host.

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What is claimed is:

1. A recombinant gene comprising a nuclcotide sequence which encodes a flagellin fusion protein, which protein comprises a flagellin sequence containing a first epitope of a Salmonella H1-d flagellin structural gene with at least one epitope of a heterologous organism inserted within the flagellin sequence, wherein the flagellin protein is capable of binding to an antiflagellin antibody, wherein the DNA encoding at least one epitope of the heterologous organism is inserted in place of the DNA which naturally occurs between the natural EcoRV sites of the Salmonella H1-d gene.

2. A plasmid selected from the group consisting of pPX1653, pPX1662, pLS411, and pROTA92-19, as deposited with the ATCC and assigned accession numbers 67688, 67687, 67686, and 67945, respectively.

3. A recombinant microorganism containing a plasmid selected from the group consisting of pPX1653, pPX1662, pLS411, and pROTA92-19, as deposited with the ATCC and assigned accession numbers 67688, 67687, 67686, and 67945, respectively.