Abstract: A method and combination for treating a cancer patient by combining two distinct immuno-therapy solutions for administration to a patient within a common time period, comprising a checkpoint inhibitor antibody component such as a PD-1 or PD-L1 antibody administered by infusion, and a TAA/ecdCD40L vaccine component administered subcutaneously, wherein an initial antibody component administered is followed by at least several successive antibody boosts and an initial vaccine component administered is followed by at least several successive vaccine boosts, both the initial and boosts of each administered within at least said common time period, wherein the combined administration of said two distinct immuno-therapy solutions provides for an enhanced therapeutic effect, over that of the therapeutic effect of either of the two distinct immuno-therapy component solutions when administered alone as monotherapy.

Abstract: An immunotherapeutic mRNA vaccine comprises a first translation unit comprising a secretable first fusion protein comprising a co-stimulatory molecule fused to a first TAA, adapted to generate a first TAA specific adaptive immune response by way of a first immunostimulatory pathway. The immunotherapeutic mRNA vaccine also comprises a second translation unit comprising a non-secretable second fusion protein comprising an identical co-stimulatory molecule fused to a second TAA identical to the first TAA, adapted to generate a second TAA specific adaptive immune response by way of a second immunostimulatory pathway, whereby the at least two immune response interact at one or more locations downstream to amplify the first TAA specific adaptive immune response.

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: A cDNA composition for reducing the virulence of Bp and reduce the cell kill and scope of the infectious disease Burkholderia pseudomallei. (Bp), which encodes fusion proteins comprised of fragments of the extracellular domains of two Bp proteins are attached to the extracellular domain (ecd) of the potent immunostimulatory protein CD40 ligand (CD40L) in order to increase the levels of neutralizing antibodies which will interfere with the function of the extracellular domains of three Bp protein peptide fragments, OMP85, VgrG5 and Hcp-1, in order to protect against a lethal challenge of Bp.

Abstract: A composition/vaccine to intensify and expand the magnitude of the host immune response against the Ag 85 and ESAT6 proteins thereby blocking the inhibitory effect of these two classes of secreted proteins, and thus promoting the clearing or control of the MTb infection. Fusion proteins are created between immunogenic fragments of the soluble secreted MTb proteins Ag 85 and ESAT6 (which are inhibitors of the immune response) and the extracellular domain (ecd) of the immunostimulatory protein ecdCD40 ligand (ecdCD40L). Fusion proteins are created using both Ag85 and ESAT-6 immunogenic peptides and ecdCD40L, to induce a more potent immune response against the MTb than would the use of either protein (Ag85 or ESAT-6) alone. Both a humoral and cellular immune response are induced. The composition/vaccine further avoids the requirement for use of attenuated strains of the tubercle bacillis, to induce an immune response to the Ag85 and ESAT6 proteins.

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 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: 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: 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: Provided are methods of selecting domains of the dengue hemorrhagic fever virus E protein for generating a neutralizing antibody immune response to the dengue hemorrhagic fever virus. The method comprises priming an individual by administering a mixture of expression vectors encoding fusion proteins or the fusion proteins themselves which comprises the DHFV E antigen fragment linked to the extracellular domain of the CD40 ligand. The expression vector comprises a transcription unit encoding a secretable fusion protein, the fusion protein containing the DHFV E antigen fragment linked to the CD40 ligand. The methods may be used to immunize an individual against all four strains of dengue hemorrhagic fever virus.

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 pharmaceutical compositions and methods of inhibiting or blocking one or more virulence antigenic factors of Bacillus anthracis. Specifically, it involves the 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 an antigenic factor of Bacillus anthracis attached through a linker to the aminoterminal end of the CD40 ligand. This fusion protein has the ability to generate antibodies which prevents Bacillus anthracis infection in an individual.

Abstract: A method and combination for treating a cancer patient by combining two distinct immuno-therapy solutions for administration to a patient within a common time period, comprising a checkpoint inhibitor antibody component such as a PD-1 or PD-L1 antibody administered by infusion, and a TAA/ecdCD40L vaccine component administered subcutaneously, wherein an initial antibody component administered is followed by at least several successive antibody boosts and an initial vaccine component administered is followed by at least several successive vaccine boosts, both the initial and boosts of each administered within at least said common time period, wherein the combined administration of said two distinct immuno-therapy solutions provides for an enhanced therapeutic effect, over that of the therapeutic effect of either of the two distinct immuno-therapy component solutions when administered alone as monotherapy.

Abstract: Provided are compositions and methods of selecting at least three fragments one each from three domains of the malarial CSP for generating antigen specific CD8 effector T cells and non-cross reacting neutralizing antibody immune responses to the malarial parasite, which when administered prevent an infection of a human being when bitten by a malaria infected mosquito. The composition and method comprises priming an individual by administering a mixture of one or more adenoviral expression vectors encoding one or more fusion proteins, 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 to block the attachment to or infection of the human liver cell(s) by the malarial sporozoite.

Abstract: The present invention is directed to novel multivalent DNA vaccine compositions for inhibiting/blocking one or more virulence antigenic factors of Yersinia pestis in an individual via compositions containing fusion proteins derived from Yersinia pestis fused to the CD40 ligand. Specifically, it involves the administering of expression vectors carrying transcription units that encode fusion proteins comprising a Yersinia pestis antigenic factor fused to the aminoterminal end of the extracellular domain (ecd) of the CD40 ligand (CD40L). The first antigenic factor is a 30 amino acid region (amino acids 196-226) of LcrV outer protein and the second antigenic factor is a 127 amino acid region (amino acids 22-149) of F1 outer protein. The composition may additionally incorporate two secretable fusion proteins (amino acids 196-226 of LcrV and amino acids 22-149 of F1) or multiple antigenic factors (YpkA, YopD, YscF, YadC, OppA) in an effort to reduce the probability of immunological escape.

Abstract: The present invention is directed to novel compositions and methods against HSV (herpes simplex virus) 1 and 2. In brief, an epitope from a binding region of glycoprotein gD, important for binding or attachment of the HSV to the host cell, which is used to mediate the first essential function of infection, and three epitopes from binding regions of glycoprotein gB are used to mediate the second essential function of infection or the fusion of the HSV envelope with the cellular plasma membrane. Each of these epitopes is fused or linked with the extracellular domain of protein CD40L, to form a fusion protein, which fusion proteins are then combined in a mixture to form the inventive composition for acting against HSV 1 and 2.

Abstract: This two-step method used in the Clostridium difficile toxin transport is a unique method of delivery. The use of a vaccine (TAA/ecdCD40L) for the interdiction of this two-step delivery toxin system to reduce cell death and the death of human subjects is believed to be unique in the area of neutralizing antibodies for protection against the lethal effects of an infectious agent. The proposed composition/vaccine strategy for C difficile is to combine and administer at the same time the two compositions/vaccines for Toxin A, the one composition/vaccine for Toxin B and the one vaccine for CDTb to determine the effect of mixing these compositions/vaccines on protecting mice from a lethal dose of C difficile. This is believed to be the first time that two different tandem repeats from the contact of a ligand with its cellular receptor have been used to prevent binding of the ligand to its cellular receptor.

Abstract: The present invention relates to a vaccine comprising the insertion of three genes, the TAA/ecdCD40L EA1 and CDA, driven by promoters L-plastin/cytosinedeaminase and CMV as a three gene, three transcription unit oncolytic virus as a conditionally replication competent adenoviral vector which replicates only in tumor cells. In these transcription units, the E1A gene of the adenoviral vector as well as the cytosine deaminase gene are under the control of the L-plastin promoter, while the TAA/ecdCD40L transcription unit is under control of a the CMV promoter.

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: The present invention is directed to a composition and/or plasmid and/or vector vaccine which encodes four fragments of the GP1 Ebola protein attached to the extracellular domain of the potent immunostimulatory protein CD40 ligand, in the configuration of two compositions and/or vaccines that are mixed together, to respectively increase the levels of antibodies and CD8 effector T cells, against the lethal Ebola virus.