City of Hope

University of California

Felix Wussow

Don Jeffrey Diamond

Javier Gordon Ogembo

Lorraine Zvichapera Mutsvunguma

Flavia Chiuppesi

Peter A Barry

Murali Muniraju

David H Mulama

Heidi Contreras

Disclosed are vaccine compositions comprising a VLP comprising two or more EBV envelope glycoproteins and one or more T cell antigens and methods of preventing or treating EBV infections using the vaccine compositions. Also disclosed is an expression system or a single expression vector for co-expressing two or more EBV envelope glycoproteins simultaneously to generate a VLP vaccine. The expression system may include a single vector inserted with two or more nucleic acid sequences that encode two or more EBV envelope glycoproteins linked by one or more linking sequences such that the EBV envelope glycoproteins are co-expressed simultaneously.

Multivalent Epstein-Barr virus-like particles and uses thereof

Vaccine compositions comprising a single KSHV-LP comprising two or more KSHV glycoproteins and/or one or more T cell antigens and methods of preventing or treating KSHV infections using the vaccine compositions. An expression system or a single expression vector for co-expressing two or more KSHV glycoproteins simultaneously to generate a vaccine comprising a single virus-like particle. The expression system may include a single plasmid inserted with two or more nucleic acid sequences that encode two or more KSHV glycoproteins linked by one or more linking sequences such that the KSHV glycoproteins are co-expressed simultaneously.

Multivalent Kaposi sarcoma-associated herpesvirus-like particles and uses thereof

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.

MVA vaccine for delivery of a UL128 complex and preventing CMV infection

A vaccine composition comprising an immunologically effective amount of recombinant modified vaccinia Ankara (rMVA) virus comprising IE1, IE2 and pp65 or antigenic fragments thereof, which is genetically stable after at least 10 passages. A method of improving the stability of such rMVA upon passage by including one or more of the modifications: (1) inserting one or more nucleic acid sequences encoding the CMV antigens or antigenic fragments thereof into one or more insertion sites including but not limited to 044L/045L, IGR3, G1L/18R, and Del3 but not including Del2; (2) codon optimizing the nucleic acid sequences encoding the CMV antigens by removing consecutive cytosines or guanines; and (3) introducing one or more mutations in the amino acid sequences of the CMV antigens.

Genetically modified recombinant vaccinia ankara (RMVA) vaccines of improved stability and methods of preparation thereof

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.

Expression system for expressing herpesvirus glycoprotein complexes

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.

MVA-gH/gL-PC vaccine derived antibodies neutralizing human cytomegalovirus infectivity and methods thereof

Disclosed are vaccine-derived neutralizing antibodies (NAbs) for CMV infections and small peptides which define precise recognition elements of the antigens by the NAbs. In certain embodiments, vaccine-derived NAbs may be produced by immunizing a subject with a gH/gL/UL128/UL130/UL131A pentameric glycoprotein complex (gH/gL-PC). In certain embodiments, 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 disclosed herein. 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 are also disclosed. Kits and methods of using the vaccine-derived NAbs and small peptides disclosed herein including methods of treating or preventing CMV infection in a subject are also provided.

Growing community of inventors

Duarte, CA, United States of America

Felix Wussow