Microvax, LLC

Vaxum, LLC

Yale University

Albert B Deisseroth

Yucheng Tang

Lixin Zhang

Wei-Wei Zhang

Xiang-Ming Fang

Nagy Habib

David J Austin

Doris Pupowicz

Tao Wang

Enrica Lerma

Viet-Ahn A Nguyen

A SARS-CoV-2 immunotherapeutic targeted fusion protein regimen or vaccine in which the extracellular domain (ecd) of the CD40L immunostimulatory protein, is attached individually to mRNA encoding a Selected Fragment of the Spike Protein (SFSP), representing a different functional feature and a different domain or domain region, or both of the Spike Protein, to generate 7 distinct SFSP/ecdCD40L translation units, each translation unit being converted into a SFSP/ecdCD40L fusion protein regimen or vaccine and all combined into a single fusion protein mixture or composition for injection, preferably inter-muscularly (im). Each fragment or peptide is designed to activate a humoral and cellular immune response to a different SFSP. Each SFSP fragment or peptide, as a vaccine strategy for the SARS-CoV-2 virus, has the capability to suppress the emergence of immunological escape mutants. The fusion protein mixture or composition of multiple fragments or peptides could be incorporated in any one of several delivery platforms such as an adenoviral expression vector or an mRNA platform.

SARS-CoV-2 fusion protein vaccine/regimen

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.

Combination cancer therapy

A cDNA composition for reducing the virulence of Bp and reduce the cell kill and scope of the infectious disease. (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.

Burkholderia pseudomallei composition

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.

Composition and method against tuberculosis

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.

CD40 ligand fusion protein vaccine

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.

Adenoviral vector vaccine

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 &#x3b1;-galactosylceramide-CD1d complex (or a related bacterial or other antigen related to &#x3b1;-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&#x2014;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.

Vaccine directed to induction of immune response to protein and glycolipid antigens of bacterial cells through interaction of CD40L/CD40 receptor axis with complex of glycolipid/CD1d receptor in NKT cells and in dendritic cells

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.

Dengue hemorrhagic fever virus vaccine

Vaccine directed to induction of immune response to protein and glycolipid antigens of bacterial cells through interaction of CD4OL/CD40 receptor axis with complex of glycolipid/CD1d receptor in NKT cells and in dendritic cells

The present invention is directed to pharmaceutical compositions and methods of inhibiting or blocking one or more virulence antigenic factors of. 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 ofattached through a linker to the aminoterminal end of the CD40 ligand. This fusion protein has the ability to generate antibodies which preventsinfection in an individual.

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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.

TAA/CD4OL composition/vaccine for malaria

The present invention is directed to novel multivalent DNA vaccine compositions for inhibiting/blocking one or more virulence antigenic factors ofin an individual via compositions containing fusion proteins derived fromfused to the CD40 ligand. Specifically, it involves the administering of expression vectors carrying transcription units that encode fusion proteins comprising aantigenic 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.

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.

Vaccines for herpes simplex virus 1 and 2

This two-step method used in thetoxin 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 foris 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. 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.

Composition and method against C-difficile

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.

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Potomac, MD, United States of America

Albert B Deisseroth