Abstract: A combination of components to promote an innate and adaptive immune response comprising of a TAA/ecdCD40L vaccine and a complex between the CD1d receptor and an alpha galactosyl ceramide like glycolipid (AGCLGL), to activate NKT cells and activate the CD40 receptor on the DCs and increase the level of the adaptive immune response induced by the TAA/ecdCD40L vaccine to the TAA. The result and advantage of using both the TAA/ecdCD40L vaccine and the ?-galactosylceramide-CD1d complex (or a related bacterial or other antigen related to ?-galactosylceramide) to stimulate the immune response through the CD40L/CD40 axis on dendritic cells, is that the magnitude of the stimulation is robust and increased significantly more than additive—i.e. synergistically due to the interaction, cross-talk and/or cross-stimulation of the glycolipid-CD1d pathway and TAA/ecdCD40L pathway. As a result, a potent immune response is induced against lipid target antigens as well as protein target antigens.

Abstract: The present invention is directed to methods of suppressing the virulence of one or more virulence antigenic factors of methicillin resistant Staphylococcus aureus (MRSA). Aspects of the invention include administering of an expression vector alone or in conjunction with a fusion protein. The expression vector has a transcription unit encoding a fusion protein composed of a virulence antigenic factor of MRSA attached through a linker to the aminoterminal end of the ecd CD40 ligand. The fusion protein is composed of a virulence antigenic factor of MRSA and CD40 ligand and has the ability to generate antibodies which prevents host cell infection by suppressing virulence functions of MRSA.

Abstract: Provided are methods of generating an immune response to any of various antigens including foreign antigens such as infectious agent antigens. In general, the method comprises administering an expression vector encoding a transcription unit encoding a secretable fusion protein, the fusion protein containing the foreign antigen and CD40 ligand and also administering the encoded fusion protein. In another approach, an immune response to the foreign antigen is elicited using the encoded fusion protein without administering the vector. The invention methods may be used to immunize an individual against an infectious agent such as influenza virus. Methods of obtaining an immune response in older individuals also is described.

Abstract: Provided are methods of selecting at least three domains of the malarial CSP protein for generating non-cross reacting neutralizing antibody immune responses to the malarial parasite which prevents an infection of a human being when bitten by a malaria infected mosquito. The method comprises priming an individual by administering a mixture of adenoviral expression vectors encoding fusion proteins or the fusion proteins themselves which comprises the malarial CSP antigen fragments linked to the extracellular domain of the CD40 ligand. The adenoviral expression vector comprises a transcription unit encoding a secretable fusion protein, the fusion protein containing selected malarial sporozoite CSP antigen fragments linked to the CD40 ligand in order to block the attachment to or infection of the human liver cell(s) by the malarial sporozoite.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which encodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: The present invention is directed to methods of suppressing the virulence of one or more virulence antigenic factors of methicillin resistant Staphylococcus aureus (MRSA). Aspects of the invention include administering of an expression vector alone or in conjunction with a fusion protein. The expression vector has a transcription unit encoding a fusion protein composed of a virulence antigenic factor of MRSA attached through a linker to the aminoterminal end of the ecd CD40 ligand. The fusion protein is composed of a virulence antigenic factor of MRSA and CD40 ligand and has the ability to generate antibodies which prevents host cell infection by suppressing virulence functions of MRSA.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which encodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Provided are methods of generating an immune response to an antigen. The method comprises priming an individual by administering an expression vector encoding the antigen. The vector comprises a transcription unit encoding a secretable fusion protein, the fusion protein containing an antigen and CD40 ligand. Administration of a fusion protein containing the antigen and CD40 ligand is used to enhance the immune response above that obtained by vector administration alone. The methods may be used to generate an immune response against cancer expressing a tumor antigen such as a mucin or human papilloma viral tumor antigen and to generate an immune response against an infectious agent. Also provided is a method for simultaneously producing the expression vector and the fusion protein.

Abstract: Provided are methods of generating an immune response to an antigen. The method comprises priming an individual by administering an expression vector encoding the antigen. The vector comprises a transcription unit encoding a secretable fusion protein, the fusion protein containing an antigen and CD40 ligand. Administration of a fusion protein containing the antigen and CD40 ligand is used to enhance the immune response above that obtained by vector administration alone. The methods may be used to generate an immune response against cancer expressing a tumor antigen such as a mucin or human papilloma viral tumor antigen and to generate an immune response against an infectious agent. Also provided is a method for simultaneously producing the expression vector and the fusion protein.

Abstract: A Tularemia vaccine proposes to induce antibodies which through their binding to the target proteins of the vaccine strategy will inactivate the proteins essential to mediating the secretory function of the pilus proteins of the “type IV pilus proteins” or Tfp proteins, thereby impairing the formation of the pilus proteins on the surface of the FT which are needed for binding and entry of the FT into macrophages, and will inhibit the secretion of several factors of FT which are necessary for the virulence of the FT, and which are missing in attenuated strains of FT used in current attenuate strain vaccination strategies.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which encodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which enocodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which enocodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which encodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which enocodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: Provided are adenoviral vectors for generating an immune response to antigen. The vectors comprise a transcription unit encoding a secretable polypeptide, the polypeptide comprising a secretory signal sequence upstream of a tumor antigen upstream of CD40 ligand, which is missing all or substantially all of the transmembrane domain rendering CD40L secretable. Also provided are methods of generating an immune response against cells expressing a tumor antigen by administering an effective amount of the invention vector. Further provided are methods of generating an immune response against cancer expressing a tumor antigen in an individual by administering an effective amount of the invention vector. Still further provided are methods of generating immunity to infection by human papilloma virus (HPV) by administering an effective amount of the invention vector which enocodes the E6 or E7 protein of HPV. The immunity generated is long term.

Abstract: A liposomal methyl phosphonate oligonucleotide composition useful in treatment of chronic myeloid leukemia comprises (a) a liposome which comprises at least one phospholipid, and (b) an antisense methyl phosphonate oligonucleotide which is entrapped in the liposome. The molar ratio of phospholipid in the liposome to the methyl phosphonate entrapped in the liposome is between about 100:1 and about 10,000:1. A process for making the composition includes the steps of (a) mixing an antisense methyl phosphonate oligonucleotide in a first organic solvent with at least one phospholipid in a second organic solvent, where the molar ratio of phospholipid to methyl phosphonate is between about 100:1 and about 10,000:1, (b) lyophilizing the mixture formed in step (a), producing a lyophilized powder, (c) hydrating the lyophilized powder, and (d) sonicating the hydrated material.