Multivalent virus like particle vaccines

A vaccine comprising a mix of three different isolated and purified multivalent arbovirus Virus Like Particles (VLP) that each comprises a flavivirus capsid protein and at least one structural protein from a virus selected from Japanese Encephalitis Virus (JEV), Chikungunya virus (CHIKV), Yellow Fever Virus (YFV), and Zika virus, wherein the vaccine is a combination of three or more different flaviviral proteins in VLPs from arboviruses and the flavivirus capsid protein, wherein the three or more nucleic acids are selected from at least one of nucleic acid SEQ ID NOS:2, 4, 6, or 8;

• wherein the three or more nucleic acids are inserted into the lentiviral vector;
• wherein the three or more nucleic acid are defined further as inserted into a vector or vectors;
• or wherein at least one of the nucleic acids is defined further as a bicistronic lentiviral vector.

A cell line transformed with a nucleic acid vector comprising a nucleic acid sequence that is a consensus, a codon optimized, or both a consensus and codon optimized nucleic acid that encodes three or more different multivalent arbovirus proteins from three or more different flaviviruses in a lentiviral vector and a flavivirus capsid protein, wherein the three or more nucleic acids are selected from at least one of nucleic acid SEQ ID NOS:2, 4, 6, or 8;

• wherein the three or more nucleic acids are inserted into the lentiviral vector;
• wherein the three or more nucleic acid are defined further as inserted into a vector or vectors;
• or wherein at least one of the nucleic acids is defined further as a bicistronic lentiviral vector.

A purified multivalent mixture of three or more flavivirus Virus Like Particles (MV-VLP) that each comprising a flavivirus capsid protein and a flavivirus structural protein selected from different flaviviruses and the three or more proteins are expressed from nucleic acids of SEQ ID NO:2, 4, 6, or 8.

An immunogenic composition comprising three or more multivalent Virus Like Particles (VLP) that each comprise a flavivirus capsid protein and a structural protein selected from each of three or more different viruses selected from Japanese Encephalitis Virus (JEV), Chikungunya virus (CHIKV), Yellow Fever Virus (YFV), and Zika virus, and optionally comprises an adjuvant, wherein the three or more nucleic acids are selected from at least one of nucleic acid SEQ ID NOS:2, 4, 6, or 8;

• wherein the three or more nucleic acids are inserted into the lentiviral vector;
• wherein the three or more nucleic acid are defined further as inserted into a vector or vectors;
• or wherein at least one of the nucleic acids is defined further as a bicistronic lentiviral vector.

A method of generating an immune response to three or more different flaviviruses in a subject, the method comprising administering to the subject an effective amount of an immunogenic composition comprising three or more multivalent flavivirus Virus Like Particles (VLP) that comprises a flavivirus capsid protein and at least one structural protein selected from each of three or more different flaviviruses selected from Zika virus, Yellow Fever Virus, Japanese Encephalitis Virus, Dengue1-4 Virus, Tick Borne Encephalitis Virus, West Nile Virus, or St Louis Encephalitis Virus, wherein the three or more nucleic acids are selected from at least one of nucleic acid SEQ ID NOS:2, 4, 6, or 8;

• wherein the three or more nucleic acids are inserted into the lentiviral vector;
• wherein the three or more nucleic acid are defined further as inserted into a vector or vectors;
• or wherein at least one of the nucleic acids is defined further as a bicistronic lentiviral vector.

A nucleic acid vector comprising a lentiviral vector comprising one or more engineered restriction nuclease sites, a flavivirus capsid protein, and three or more different codon optimized proteins from three or more different flaviviruses, wherein the vector produces three or more multivalent flavivirus Virus Like Particles (MV-VLP) when in a cell, wherein the three or more nucleic acids are selected from at least one of nucleic acid SEQ ID NOS:2, 4, 6, or 8;

• wherein the three or more nucleic acids are inserted into the lentiviral vector;
• wherein the three or more nucleic acid are defined further as inserted into a vector or vectors;
• or wherein at least one of the nucleic acids is defined further as a bicistronic lentiviral vector.