Patent application EP16162688A (EP), filed 2016-03-29
Publication number: EP3184118A1
Title: RECOMBINANT ZIKA VACCINES
Abstract: The present invention relates to the provision of immunogenic or vaccine compositions comprising at least one recombinant Zika virus antigen, wherein the at least one recombinant Zika virus antigen is encoded by at least one nucleic acid sequence encoding at least one E-protein of a Zika virus or a fragment thereof. Further provided are nucleic acid molecules and a recombinant chimeric virus encoding and/or comprising selected antigens from a Zika virus, which are suitable as vaccine compositions. Preferably, the sequences encoding at least one Zika virus antigens suitable for eliciting an immune response are operably linked to a non-flavivirus derived vector backbone and do not contain capsid or non-structural proteins derived from a Zika virus. Further provided are methods for purifying the recombinant chimeric virus particles or the immunogenic composition. Finally, there is provided an immunogenic/vaccine composition for use in a method of preventing or treating a Zika virus disease.
IPC codes: A61K  39/    12            A I
C07K  14/   005            A I
Claims: number: 1
text: An immunogenic composition comprising at least one recombinant Zika virus antigen, wherein the at least one recombinant Zika virus antigen is encoded by at least one nucleic acid sequence encoding at least one E-protein of a Zika virus or a fragment thereof, wherein the at least one nucleic acid sequence does not comprise a further nucleic acid sequence encoding non-structural proteins of a flavivirus, wherein the nucleic acid sequence encoding the at least one recombinant Zika virus antigen is operably linked to a vector backbone, preferably a non flavivirus derived vector backbone, the immunogenic composition comprising at least one pharmaceutically and/or veterinarially acceptable carrier and/or excipient.
number: 2
text: The immunogenic composition according to claim 1,
number: 3
text: The immunogenic composition according to claim 1 or 2, wherein the vector backbone is selected from the group consisting of a measles virus derived scaffold, a lentivirus derived scaffold or a modified vaccinia Ankara derived scaffold.
number: 4
text: The immunogenic composition according to any one of claims 1 to 3, wherein the vector backbone is derived from an attenuated virus measles virus strain, the measles virus strain preferably being selected from the group consisting of the Schwarz strain, the Zagreb strain, the AIK-C strain and the Moraten strain.
number: 5
text: The immunogenic composition according to any one of claims 1 to 4, wherein the immunogenic composition comprises at least one nucleic acid sequence or at least one amino acid sequence encoded by the at least one nucleic acid sequence, wherein the at least one nucleic acid or amino acid sequence is selected from the group consisting of SEQ ID NOs: 27 to 39, 53 to 58, 61 to 66, 109 to 139, 151 and 152 or a sequence having at least 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence homology thereto provided that the homologous sequence, optionally after expression, still encodes at least one functional Zika virus antigen.
number: 6
text: A nucleic acid molecule comprising at least one nucleic acid sequence, the at least one nucleic acid sequence comprising a nucleic acid sequence encoding at least one E-protein of a Zika virus or a fragment thereof, and a nucleic acid sequence encoding at least one E-protein signal sequence for a Zika virus E-protein or for a fragment thereof, and optionally comprising a nucleic acid sequence encoding at least one pre-membrane protein of a Zika virus or a fragment thereof and optionally comprising a nucleic acid sequence encoding at least one pre-membrane protein signal sequence for a Zika virus prM protein or for a fragment thereof, wherein the nucleic acid sequence encoding the at least one E-protein of a Zika virus or fragment thereof, and optionally also encoding the at least one pre-membrane protein of a Zika virus or fragment thereof are independently derived from SEQ ID NOs: 1 to 13 and 67 to 87, wherein the nucleic acid molecule does not comprise a nucleic acid sequence encoding a C-protein of a flavivirus and wherein the nucleic acid molecule does not comprise a nucleic acid sequence encoding non-structural proteins of a flavivirus,
number: 7
text: The nucleic acid molecule according to claim 6, wherein the at least one nucleic acid sequence is selected from the group consisting SEQ ID NOs: 53 to 56 or 63 and 64 or a sequence having at least 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence homology thereto provided that the homologous sequence after expression still encodes a functional Zika virus antigen.
number: 8
text: A recombinant chimeric virus comprising a vector backbone as defined in any one of claims 1, 3 or 4, and comprising at least one nucleic acid molecule according to claims 6 or 7, or comprising at least one nucleic acid sequence as defined in any one of claims 1, 2 or 5.
number: 9
text: The recombinant chimeric virus according to claim 8, wherein the chimeric virus is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 57 or 58, or a sequence of SEQ ID NO: 60 comprising a sequence encoding a sequence of SEQ ID NOs: 27 to 39, 40 to 52, 109 to 129 or 130 to 150 inserted between position 3544 and 3545 of SEQ ID NO:60 or a sequence having at least 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence homology thereto provided that the homologous sequence after expression still encodes chimeric recombinant virus particles.
number: 10
text: A method for producing a recombinant chimeric virus according to claims 8 or 9, or for producing an immunogenic composition according to any one of claims 1 to 5, the method comprising the following steps:
number: 11
text: The method of claim 10, comprising a purification step (iv), wherein the purification step comprises purification by means of chromatography.
number: 12
text: The method of claims 10 or 11, wherein the at least one host cell is selected from the group consisting of Vero cells, chicken embryo fibroblast cells, HEK293 cells, HeLa cells, fetal rhesus lung cells or MRC5 cells.
number: 13
text: The method of any one of claims 10 to 12, wherein the method comprises a further step, comprising
(vii) separating recombinant subviral particles from infectious particles.
number: 14
text: An immunogenic composition, preferably a vaccine composition, comprising an immunogenic composition according to any one of claims 1 to 5, or comprising a nucleic acid molecule according to claims 6 or 7, or comprising a recombinant chimeric virus according to claims 8 or 9, for use in a method of preventing or treating a Zika virus disease in a subject.
number: 15
text: The immunogenic composition or the vaccine composition for use in a method of preventing or treating a Zika virus disease according to claim 14, wherein the composition is characterized by a content of contaminating host cell DNA of less than 100 pg/dosis, preferably of less than 75 pg/dosis, more preferably of less than 50 pg/dosis, even more preferably less than 25 pg/dosis and most preferably of less than 10 pg/dosis, wherein one dosis represents one dosis comprising the immunogenic or the vaccine composition to be administered to a subject in need thereof as a single dose.
Office action: search_report, dated 2017-06-28
Rejection reasons: novelty_epc_54
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Final disposition: pending (2017-06-28)