The University of Texas System

David W Niesel

Gary R Klimpel

Ashok K Chopra

Alan D Barrett

Haolin Ni

Jian Sha

Christopher Robb

Linda H Phillips

J Scott Moncrief

The present invention concerns the use of methods and compositions to prophylactically or therapeutically vaccinate a subject against a pathogen or disease. Embodiments of the invention include the production of an attenuated bacterium from the family Enterobacteriaceae with a non-functional lipoprotein for use as a vaccine or as a vaccine vector for delivering antigens to a subject to be vaccinated. In certain embodiments, a bacterium of the Enterobacteriaceae family lacking a wild type LP, for examplelacking a wild type LP, may be produced and used as a vaccine or vaccine vector.

Methods and compositions for vaccination against or involving enterobacteriaceae bacteria

The present invention provides a Mycobacterium-E. coli shuttle vector containing sequences coding for a tribrid fusion containing the M. leprae 18kDa antigen sequence, a phoA protein antigen sequence and a non-mycobacterial, non-E.coli heterologous protein antigen sequence. Also provided is a method of producing protective immunity in an animal or human host in need of such treatment, comprising the step of administering to said animal or human host an effective dose of recombinant mycobacteria carrying the vector of the present invention.

Non-antibiotic system for selection of recombinant mycobacteria

Cytokine receptors for tumor necrosis factor e which are found on microorganisms may, if bound with exogenous TNF.alpha., enhance the response of natural killer cells activated by the microorganisms, or increase TNF.alpha. production by peripheral blood lymphocytes treated with the microorganisms. Microorganisms with receptor-bound exogenous TNF.alpha. have enhanced cellular invasion ability which may change the immune response thereto. Clinical and pharmaceutical applications of these discoveries are provided.

Method of using cytokine receptors on microorganism

The invention relates to nucleic acid segments useful in the construction of expression vectors for expression of heterologous polypeptides directed to particular areas of the host cell. Selected constructs direct production of polypeptides to the outer membrane surface of the cell. Other constructs direct expression of heterologous polypeptides to the inner membrane/periplasm of the host cell. Transformed host cells are potentially useful for the production of vaccines or immunogens elicited in response to antigens expressed on the outer membranes of the host cells.

Membrane expression of heterologous genes

Cytokine receptors for tumor necrosis factor .alpha. which are found on microorganisms may, if bound with exogenous TNF.alpha., enhance the response of natural killer cells activated by the microorganisms, or increase TNF.alpha. production by peripheral blood lymphocytes treated with the microorganisms. Microorganisms with receptor-bound exogenous TNF.alpha. have enhanced cellular invasion ability which may change the immune response thereto. Clinical and pharmaceutical applications of these discoveries including vaccines with increased efficacy are provided.

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League City, TX, United States of America

David W Niesel