Abstract: T cells expressing a chimeric antigen receptor and a T cell receptor specific for CMV (bi-specific T cells) are described as a methods for using such cells in immunotherapy. In the immunotherapy methods, the recipient can be exposed to a CMV vaccine in order to expand and/or stimulate the be-specific T cells.

Abstract: Disclosed herein are CMV-specific CARs. In some embodiments. the present invention is directed to a method of treating, reducing, or inhibiting an infection by a cytomegalovirus in a subject, which comprises administering to the subject (a) an expression vector that encodes a CMV-specific CAR as described herein, or (b) one or more cells that are transduced with the expression vector.

Abstract: A method for treating a patient comprising: (a) providing a composition comprising a population of T cells expressing both a chimeric antigen receptor (CAR) and a T cell receptor specific for a cytomegalovirus (CMV) antigen; (b) administering the composition to the patient; and (c) administering to the patient a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein IE2 (e5) either prior to or subsequent to administering the composition comprising a population of T cells to the patient is described.

Abstract: An expression system for expressing a herpesvirus glycoprotein complex including a vector inserted with two or more nucleic acid sequences that encode two or more subunits of a herpesvirus glycoprotein complex linked by one or more linking sequences such that the subunits are co-expressed simultaneously and self-processed to assemble into a glycoprotein complex. The expression system or the vector can be included in a vaccine composition. The vaccine composition can be used for preventing or treating herpesvirus infections.

Abstract: In one embodiment, an expression system for expressing a UL128 complex is provided herein. The expression system may include a bacterial artificial chromosome (BAC) construct, wherein the BAC construct comprises a viral vector inserted with a set of DNA sequences that encode a UL128 complex. In another embodiment, a vaccine composition for preventing HCMV infection is provided. The vaccine composition may include a viral or bacterial vector capable of expressing a UL128 complex and a pharmaceutically acceptable carrier, adjuvant, additive or combination thereof or additional vector expressing a protein adjuvant. The viral vector may be an MVA and the UL128 complex includes five HCMV proteins or antigenic fragments thereof: UL128, UL130, UL131A, gL, and gH. In some embodiments, the viral vector is further inserted with one or more additional DNA sequences that encode one or more additional HCMVHCMV proteins or antigenic fragments thereof such as pp65, gB or both, or such as gM/gN or gO.

Abstract: Disclosed is a method of treating or preventing a CMV infection in a recipient of a hematopoietic cell transplant (HCT). The method entails administering an effective amount of a CMV Triplex vaccine composition to a donor and/or recipient of the hematopoietic cells.

Abstract: Disclosed are synthetic modified vaccinia ankara (MVA)-based vaccines for preventing or treating coronavirus infections and methods of producing the vaccines. Specifically, the disclosure provides a vaccine composition comprising: (i) a single synthetic DNA fragment or two or more synthetic DNA fragments comprising the entire genome of an MVA, and (ii) one or more DNA sequences encoding one or more coronavirus antigens, subunits, or fragments thereof, inserted in one or more insertion sites of the MVA for preventing or treating coronavirus infections.

Abstract: A vaccine comprising an immunologically effective amount of recombinant modified vaccinia Ankara (rMVA) virus which is genetically stable after serial passage and produced by a) constructing a transfer plasmid vector comprising a modified H5 (mH5) promoter operably linked to a DNA sequence encoding a heterologous foreign protein antigen, wherein the expression of said DNA sequence is under the control of the mH5 promoter; b) generating rMVA virus by transfecting one or more plasmid vectors obtained from step a) into wild type MVA virus; c) identifying rMVA virus expressing one or more heterologous foreign protein antigens using one or more selection methods for serial passage; d) conducting serial passage; e) expanding an rMVA virus strain identified by step d); and f) purifying the rMVA viruses from step e) to form the vaccine.

Abstract: In one embodiment, an expression system for expressing a UL128 complex is provided herein. The expression system may include a bacterial artificial chromosome (BAC) construct, wherein the BAC construct comprises a viral vector inserted with a set of DNA sequences that encode a UL128 complex. In another embodiment, a vaccine composition for preventing HCMV infection is provided. The vaccine composition may include a viral or bacterial vector capable of expressing a UL128 complex and a pharmaceutically acceptable carrier, adjuvant, additive or combination thereof or additional vector expressing a protein adjuvant. The viral vector may be an MVA and the UL128 complex includes five HCMV proteins or antigenic fragments thereof: UL128, UL130, UL131A, gL, and gH. In some embodiments, the viral vector is further inserted with one or more additional DNA sequences that encode one or more additional HCMVHCMV proteins or antigenic fragments thereof such as pp65, gB or both, or such as gM/gN or gO.

Abstract: Disclosed are synthetic MVA-based vaccines for preventing or treating infections caused by a coronavirus or variants thereof.

Abstract: Provided herein are, inter alia, methods and compositions including T cells expressing (i) a recombinant CAR protein which includes a peptide binding site and is capable of specifically binding cancer-specific antigens and (ii) a T cell receptor specific for a viral antigen (e.g., a CMV pp65 protein). The engineered T cells provided herein may be used in combination with a viral vaccine (e.g. cytomegalovirus (CMV) Triplex Vaccine) to treat a variety of cancers. The methods described herein also permit in vivo expansion of CMV-specific CAR T cells, instead of or in addition to ex vivo expansion, avoiding excessive T cell exhaustion that results in some cases from ex vivo manufacturing.

Abstract: An expression system for expressing a herpesvirus glycoprotein complex including a vector inserted with two or more nucleic acid sequences that encode two or more subunits of a herpesvirus glycoprotein complex linked by one or more linking sequences such that the subunits are co-expressed simultaneously and self-processed to assemble into a glycoprotein complex. The expression system or the vector can be included in a vaccine composition. The vaccine composition can be used for preventing or treating herpesvirus infections.

Abstract: Disclosed are methods of producing poxvirus-based vectors or recombinant poxvirus-based vectors from naturally derived, chemically synthesized DNA fragments, or a combination of naturally derived and chemically synthesized DNA fragments. One or more DNA sequences encoding one or more antigens, subunits or fragments thereof or other heterologous gene sequences are inserted in one or more poxvirus insertion sites in one or more DNA fragments. The methods include transfecting a host cell with one or more circular or linear DNA fragments such that a poxvirus or recombinant poxvirus is reconstituted in the host cell, the reconstituted poxvirus or recombinant poxvirus comprising the genome of a desired poxvirus. Also disclosed are poxviruses or recombinant poxviruses produced by the technology and uses thereof.

Abstract: The disclosure provides, inter alia, methods and materials involved in treating cancer using a p53 vaccine in combination with a PD-1 pathway inhibitor.

Abstract: A method for treating a patient comprising: (a) providing a composition comprising a population of T cells expressing both a chimeric antigen receptor (CAR) and a T cell receptor specific for a cytomegalovirus (CMV) antigen; (b) administering the composition to the patient; and (c) administering to the patient a viral vector encoding: (i) CMV pp65 and (ii) a fusion protein comprising exon 4 of CMV protein IE1 (e4) and exon 5 of CMV protein 1E2 (e5) either prior to or subsequent to administering the composition comprising a population of T cells to the patient is described.

Abstract: Provided herein, inter alia, are compositions and kits comprising a bacterial cell and a tumor penetrating agent. Also provided are methods of treating cancer in a subject including the step of administering to the subject an effective amount of a bacterial cell and a tumor penetrating agent. Provided are methods of stimulating an immune system in a subject. The methods include administering to the subject an effective amount of a bacterial cell and a tumor penetrating agent. Also provided are methods of enhancing delivery of an anti-cancer agent to a tumor cell including the step of contacting the tumor cell with a bacterial cell, a tumor penetrating agent and an anti-cancer agent.

Abstract: An expression system for expressing a herpesvirus glycoprotein complex including a vector inserted with two or more nucleic acid sequences that encode two or more subunits of a herpesvirus glycoprotein complex linked by one or more linking sequences such that the subunits are co-expressed simultaneously and self-processed to assemble into a glycoprotein complex. The expression system or the vector can be included in a vaccine composition. The vaccine composition can be used for preventing or treating herpesvirus infections.

Abstract: Vaccine-derived neutralizing antibodies (NAbs) for CMV infections and small peptides which define precise recognition elements of the antigens by the NAbs. The vaccine-derived NAbs may be produced by immunizing a subject with a gH/gL/UL128/UL130/UL131A pentameric glycoprotein complex (gH/gLPC). The vaccine-derived NAbs may have properties similar or identical to those of NAbs induced in a subject naturally infected with CMV. Native and non-native small peptides from UL128 and gH have been defined by mapping epitopes and deriving artificial sequences which are minimal recognition elements of vaccine-derived NAbs. These small peptides can be used to elicit vaccine-derived NAbs that prevent CMV entry into susceptible cell types and protect humans from infection and disease. Multivalent vaccines comprising these small peptides and/or epitopes as well as methods of using the vaccine-derived NAbs and small peptides for treating or preventing CMV infection in a subject are also provided.

Abstract: Provided herein are compositions and methods to treat tumors that include attenuated facultative anaerobic bacterium. The bacterium includes a nucleic acid molecule encoding a recombinant extracellular matrix degrading enzyme operably linked to a promoter.

Abstract: Provided herein are, inter alia, methods and compositions including T cells expressing (i) a recombinant CAR protein which includes a peptide binding site and is capable of specifically binding cancer-specific antigens and (ii) a T cell receptor specific for a viral antigen (e.g., a CMV pp65 protein). The engineered T cells provided herein may be used in combination with a viral vaccine (e.g. cytomegalovirus (CMV) Triplex Vaccine) to treat a variety of cancers. The methods described herein also permit in vivo expansion of CMV-specific CAR T cells, instead of or in addition to ex vivo expansion, avoiding excessive T cell exhaustion that results in some cases from ex vivo manufacturing.