The present invention describes specific engineering of the hantavirus spike proteins with modifications to stabilize (Gn/Gc).sub.n heterodimer contacts and/or Gc homodimer contacts and/or Gn/Gn oligomer contacts on the spike with the purpose of using them as immunogens in next-generation vaccine design. Said spike proteins have been covalently stabilized by at least one disulphide inter-chain bond between Gn/Gc heterodimers and/or between Gc homodimers and/or between Gn homo-oligomers as they are presented at the surface of infectious virions. It also involves spike stabilization by introduction of cavity-filling amino acids with a bulky side chain at the above-mentioned contacts. Said spike proteins can be soluble Gn/Gc ectodomains in solution and/or incorporated as (Gn/Gc).sub.n hetero-oligomers onto virus-like particles (VLPs) and/or used for pseudotyping virus vectors and/or form part of a stabilized recombinant virus, wherein said spike proteins can be used to select ligands and/or can be used for preventing or treating infections by one or more hantaviruses.

The invention contemplates a new synthetic, codon-optimized Sin Nombre virus (SNV) full-length M gene open reading frame (ORF) that encodes a unique consensus amino acid sequence. The SNV ORF was cloned into a plasmid to form the first stable recombinant SNV full-length M gene that elicits neutralizing antibodies. The gene can be engineered into a vaccine system, and is useful to protect mammals against infection with Sin Nombre virus.

The present invention relates to enveloped RNA viruses. The invention in particular relates to the generation of superior antigens for mounting an immune response by first identifying then mutating the immunosuppressive domains in fusion proteins of enveloped RNA viruses resulting in decreased immunosuppressive properties of viral envelope proteins from the viruses.

Hantavirus spike proteins with modifications to stabilize (Gn/Gc)n heterodimer contacts and/or Gc homodimer contacts and/or Gn/Gn oligomer contacts on the spike to enable their use as immunogens in next-generation vaccine design. The spike proteins have been covalently stabilized by at least one disulphide inter-chain bond between Gn/Gc heterodimers and/or between Gc homodimers and/or between Gn homo-oligomers as they are presented at the surface of infectious virions. Also, spike stabilization by introduction of cavity-filling amino acids with a bulky side chain at the above-mentioned contacts. The spike proteins can be soluble Gn/Gc ectodomains in solution and/or incorporated as (Gn/Gc)n hetero-oligomers onto virus-like particles (VLPs) and/or used for pseudotyping virus vectors and/or form part of a stabilized recombinant virus. The spike proteins can be used to select ligands and/or can be used for preventing or treating infections by one or more hantaviruses.

The invention contemplates a new synthetic, codon-optimized Sin Nombre virus (SNV) full-length M gene open reading frame (ORF) that encodes a unique consensus amino acid sequence. The SNV ORF was cloned into a plasmid to form the first stable recombinant SNV full-length M gene that elicits neutralizing antibodies. The gene can be engineered into a vaccine system, and is useful to protect mammals against infection with Sin Nombre virus.

A synthetic, codon-optimized Hantaan virus (HTNV) full-length M gene open reading frame that consists of a unique nucleotide sequence encoding HTNV proteins. This synthetic gene was cloned into a plasmid to form the first optimized HTNV full-length M gene that elicits neutralizing antibodies in animals when delivered in combination with a similarly optimized Puumala virus (PUUV) DNA vaccine. The invention obviates the need for an extraneous gene sequence that was previously required for expression of the non-optimized HTNV gene. The synthetic gene is engineered into a molecular vaccine system to prevent hemorrhagic fever with renal syndrome (HFRS) caused by infection with HTNV, SEOV, or DOBV. Alternatively, it can be combined with the optimized PUUV DNA vaccine to protect against HFRS caused by any hantavirus.

The present invention relates to enveloped RNA viruses. The invention in particular relates to the generation of superior antigens for mounting an immune response by first identifying then mutating the immunosuppressive domains in fusion proteins of enveloped RNA viruses resulting in decreased immunosuppressive properties of viral envelope proteins from the viruses.

A synthetic, codon-optimized Hantaan virus (HTNV) full-length M gene open reading frame that consists of a unique nucleotide sequence encoding HTNV proteins. This synthetic gene was cloned into a plasmid to form the first optimized HTNV full-length M gene that elicits neutralizing antibodies in animals when delivered in combination with a similarly optimized Puumala virus (PUUV) DNA vaccine. The invention obviates the need for an extraneous gene sequence that was previously required for expression of the non-optimized HTNV gene. The synthetic gene is engineered into a molecular vaccine system to prevent hemorrhagic fever with renal syndrome (HFRS) caused by infection with HTNV, SEOV, or DOBV. Alternatively, it can be combined with the optimized PUUV DNA vaccine to protect against HFRS caused by any hantavirus.

A synthetic, codon-optimized Hantaan virus (HTNV) full-length M gene open reading frame that consists of a unique nucleotide sequence encoding HTNV proteins. This synthetic gene was cloned into a plasmid to form the first optimized HTNV full-length M gene that elicits neutralizing antibodies in animals when delivered in combination with a similarly optimized Puumala virus (PUUV) DNA vaccine. The invention obviates the need for an extraneous gene sequence that was previously required for expression of the non-optimized HTNV gene. The synthetic gene is engineered into a molecular vaccine system to prevent hemorrhagic fever with renal syndrome (HFRS) caused by infection with HTNV, SEOV, or DOBV. Alternatively, it can be combined with the optimized PUUV DNA vaccine to protect against HFRS caused by any hantavirus.

A synthetic, codon-optimized Hantaan virus (HTNV) full-length M gene open reading frame that consists of a unique nucleotide sequence encoding HTNV proteins. This synthetic gene was cloned into a plasmid to form the first optimized HTNV full-length M gene that elicits neutralizing antibodies in animals when delivered in combination with a similarly optimized Puumala virus (PUUV) DNA vaccine. The invention obviates the need for an extraneous gene sequence that was previously required for expression of the non-optimized HTNV gene. The synthetic gene is engineered into a molecular vaccine system to prevent hemorrhagic fever with renal syndrome (HFRS) caused by infection with HTNV, SEOV, or DOBV. Alternatively, it can be combined with the optimized PUUV DNA vaccine to protect against HFRS caused by any hantavirus.