Aeras Global Tb Vaccine Foundation

Aeras Global Tuberculosis Vaccine Foundation

Ronggai Sun

Jerald C Sadoff

David M Hone

John Fulkerson

Avigdor Shafferman

Anat Zvi

Naomi Ariel

Rosemary Chang

David Michael Hone

strains that have an enhanced ability to elicit a MHC-Class I-restricted CD8T cell immune response are provided. Thestrains are genetically engineered to express: a endosomalytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of thefrom endosomes into the cytoplasm of the cell; and antigens of interest, such as tuberculosis antigens. The invention also provides vaccine preparations containing suchstrains.

Recombinant BCG strains with enhanced ability to escape the endosome

Recombinantstrains with improved vaccinal properties for use as vaccinating agents are provided. The parent strains of the recombinantstrains are selected for their potent immunogenicity. Thestrains do not display antibiotic resistance, and do not exhibit horizontal transfer to gram-negative bacteria.

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A vaccine against(Mtb) is provided. The vaccine comprises a recombinant Bacille Calmette-Guerin (BCG) subunit-based vaccine in which one or more Mtb antigens and one or more Mtb resuscitation or reactivation antigens are overexpressed, and in which at least a portion of the DosR regulon is up-regulated. The vaccine is protective against active Mtb infection both pre- and post-exposure to Mtb, and thus prevents disease symptoms due to the recurrence of a latent Mtb infection.

strains that have an enhanced ability to elicit a MHC-Class I-restricted CD8T cell immune response are provided. Thestrains are genetically engineered to express: a endosomolytic protein that is active at neutral pH (e.g. Perfringolysin O), permitting escape of thefrom endosomes into the cytoplasm of the cell; and antigens of interest, such as tuberculosis antigens. The invention also provides vaccine preparations containing suchstrains.

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Ellicott City, MD, United States of America

Ronggai Sun