The present invention relates to polynucleotides comprising a sequence of a live, infectious, attenuated Flavivirus wherein a nucleotide sequence encoding at least a part of a Filovirus glycoprotein is located at the intergenic region between the E and NS1 gene of said Flavivirus, such that a chimeric virus is expressed, characterised in that the encoded sequence C terminally of the E protein of said Flavivirus and N terminally of the signal peptide of the NS1 protein of said Flavivirus comprises in the following order: a further signal peptide of a Flavivirus NS1 protein, a filovirus glycoprotein wherein the N terminal signal peptide is absent, a TM domain of a flaviviral E protein.

The present invention relates to polynucleotides comprising a sequence of a live, infectious, attenuated Flavivirus wherein a nucleotide sequence encoding at least a part of a arenavirus glycoprotein protein is located at the intergenic region between the E and NS1 gene of said Flavivirus, such that a chimeric virus is expressed, characterised in that the encoded sequence C terminally of the E protein of said Flavivirus and N terminally of the signal peptide of the NS1 protein of said Flavivirus comprises in the following order:—a further signal peptide of a Flavivirus NS1 protein,—an arenavirus Glycoprotein protein lacking the N terminal signal sequence and the GP2 transmembrane domain,—a TM1 and TM2 domain of a flaviviral E protein.

The invention relates to polynucleotides comprising the sequence of a flavivirus preceded by a sequence encoding an N terminal part of a flavivirus Capsid protein, an immunogenic protein, or a part thereof comprising a an immunogenic peptide, and a 2A cleaving peptide, and to the virus encoded by such sequences. The invention further relates to the use of such polynucleotides and viruses as vaccines.

Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.

The invention relates to the use of a recombinant porcine adeno-associated virus (AAV) vector comprising a peptide-modified porcine AAV serotype 1 (AAVpol) capsid in gene therapy of muscle and/or central nervous system (CNS) disorders, in particular neuromuscular diseases such as genetic neuromuscular diseases.

The present disclosure relates to compositions and methods for investigating Zika virus (ZIKV) biology and pathogenicity. The present disclosure provides genetically stable viral vectors to produce functional RNA transcripts of ZIKV cDNAs. In particular, the present disclosure provides full-length infectious cDNAs as bacterial artificial chromosomes for spatiotemporally distinct and genetically divergent ZIKVs. The present disclosure also provides methods of generating a genetically engineered attenuated ZIKV using the genetically stable viral vectors described herein.

Embodiments herein report compositions, uses and manufacturing of dengue virus constructs and live attenuated dengue viruses. Some embodiments concern a composition that includes, but is not limited to, a tetravalent dengue virus composition. In certain embodiments, compositions can include constructs of one or more serotypes of dengue virus, such as dengue-1 (DEN-1) virus, dengue-2 (DEN-2) virus, dengue-3 (DEN-3) or dengue-4 (DEN-4) virus constructs. In other embodiments, constructs disclosed herein can be combined in a composition to generate a vaccine against more one or more dengue virus constructs that may or may not be subsequently passaged in mammalian cells.

The present invention relates to chimeric yellow fever—Zika strains and attenuated versions thereof, wherein the nucleotide sequence encoding the signal sequence and prME protein of said yellow virus is replaced by a nucleotide sequence encoding the signal sequence and the prME protein of a Zika virus.

Chimeric flaviviruses that include non-coding regions, non-structural proteins, a capsid (C) protein and a portion of a premembrane (prM) signal sequence from an attenuated or wild-type dengue serotype 2 virus (DENV-2), and a portion of a prM signal sequence, a prM protein and at least a portion of an envelope (E) protein from a Zika virus (ZIKV) are described. Also described are immunogenic compositions and methods for eliciting an immune response in a subject, such as an immune response directed against ZIKV.

The invention relates to polynucleotides comprising a sequence of a live, infectious, attenuated Flavivirus wherein a nucleotide sequence encoding the S1 and S2 subunits of a coronavirus Spike protein is located, such that a chimeric virus is expressed.