Compositions, methods and uses for dengue virus serotype-4 constructs

摘要

Embodiments herein report compositions, methods and uses for dengue-4 (DENV-4) virus constructs. Some embodiments concern a composition that includes, but is not limited to, DENV-4 virus constructs alone or in combination with other constructs, can be used in a vaccine composition to induce an immune response in a subject. In certain embodiments, compositions can include constructs of more than one serotypes of dengue virus, such as dengue-1 virus, dengue-2 virus, or dengue-3 virus in combination with DENV-4 virus constructs disclosed herein. In other embodiments, DENV-4 constructs disclosed herein can be combined in a composition with other flavivirus constructs to generate a vaccine against more than one flavivirus. Other embodiments provide methods and uses for DENV-4 virus constructs in vaccine compositions that when administered to a subject induce an immune response in the subject against DENV-4 that is improved by modified constructs compared to other vaccine compositions.

主权项

1. A nucleic acid molecule comprising a chimeric flavivirus construct comprising nucleic acid sequences encoding nonstructural proteins and one or more structural proteins from a live, attenuated dengue-2 virus and at least encoding one or more structural proteins from a second dengue virus, the second flavivirus is selected from the group dengue-1, dengue-3 or dengue-4 virus wherein the chimeric construct further comprises one or more mutations comprising, a mutation in an envelope (E) protein at an amino acid position synonymous of dengue 4 to amino acid 417 when the E protein is from the second flavivirus wherein the mutation in the envelope (E) protein at the position synonymous to amino acid 417 changes glutamic acid to a positively charged residue; a mutation in the capsid protein at an amino acid position synonymous to amino acid 107 in the attenuated dengue-2 wherein the mutation in the capsid (C) protein at the position synonymous to amino acid 107 changes cysteine to an aromatic amino acid residue in the attenuated dengue-2, and a mutation in NS4A at an amino acid position synonymous to amino acid position 17 in the attenuated dengue-2.