The General Hospital Corporation

Harvard College

Virus Research Institute

Vaccine Technologies, Incorporated

Yichen Lu

Huyen Cao

Bryan E Roberts

Lendon G Payne

Samuel I Miller, Iii

Sharon A Jenkins

Kevin Killeen

Neal Touzjian

Amie Strong

Huishan Guo

Nicholas Kushner

Zhenghui Xu

Wenbiao Zheng

The present invention is directed to a method for promoting or stimulating a cell-mediated immune response to an antigen, by administering a target antigen (such as a protein) with a transport factor that contains a fragment of a bipartite protein exotoxin, but not the corresponding protective antigen. Preferred transport factors include the protective antigen binding domain of lethal factor (LFn) from, consisting of amino acids 1-255, preferably a fragment of at least 80 amino acids that shows at least 80% homology to LFn, and a fragment of about 105 amino acids from the carboxy portion that does not bind PA. The target antigen can include any molecule for which it would be desirable to elicit a CMI response, including viral antigens and tumor antigens.

Methods and compositions for promoting a cell-mediated immune response

Described are compositions and methods for detecting or monitoring the ability of an individual to mount a cell mediated immune response to a target antigen. Methods rely in part upon the physical association, e.g., by fusion, of a Lethal Factor (LF) polypeptide with a target antigen. The LF polypeptide moiety, including, for example, an LFn polypeptide moiety, serves as a transport factor to deliver target antigens, including full length target polypeptides, to the cytosol of an intact, living immune cell from an individual. Measurement of a cytokine response by the immune cell from the individual provides a read out of a cell mediated immune response. The methods and compositions described provide diagnostic as well as prognostic information and can guide the direction of therapy.

Methods and compositions for diagnostic assays for measuring cell mediated immune response

The present invention is directed to a method for delivering exogenous proteins to the cytosol, by binding a target antigen (such as a protein) to a transport factor that contains a fragment of a bipartite protein exotoxin, but not the corresponding protective antigen. Preferably, the target antigen is fused to the transport factor. Preferred transport factors include the protective antigen binding domain of lethal factor (LFn) from, consisting of amino acids 1-255, preferably a fragment of at least 80 amino acids that shows at least 80% homology to LFn, and a fragment of about 105 amino acids from the carboxy portion that does not bind PA. The target antigen can include any molecule for which it would be desirable to elicit a CMI response, including viral antigens and tumor antigens.

Methods of delivery of exogenous proteins to the cytosol and uses thereof

A composition and method for inducing a protective immune response to HIV-1 in an individual, of (a) a replication incompetent HIV-1, HIV-1 pseudovirus, HIV-1 VLP or oligomeric gp120; and (b) a water soluble polyphosphazene polyelectrolyte, wherein (a) and (b) are present in an amount effective to induce a protective immune response against HIV-1.

HIV-1 prophylactic composition and method

A modified Salmonella, wherein the wild type pag gene such as pagC has been replaced by a gene encoding a truncated pag gene such as pagC gene fused to a heterologous DNA segment, is disclosed. This modification significantly attenuates the virulence of the Salmonella. In addition, immune reaction to the portion of the fusion protein encoded by the heterologous gene can be generated. Uses of the vector, including its use in a drug screen are also disclosed.

Salmonella vectors encoding truncated pag fusion protein, method of

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Wellesley, MA, United States of America

Yichen Lu