ZIKA VIRUS VACCINE
The present disclosure relates to vaccines and methods for the prevention and treatment of Zika virus infection. Particularly, the present disclosure relates to viral and DNA vaccine vectors which includes or encode for secreted immunogenic peptides of NS1 that eliciting a protective immune response and prevent Zika virus infection of a subject.
1 . A pharmaceutical composition including:
a nucleic acid molecule including a sequence encoding an immunogenic peptide including a portion of the non-structural protein 1 (NS1 protein) of Zika virus, the nucleic acid further encoding a heterologous signal peptide operatively linked to the immunogenic peptide, wherein the immunogenic peptide, when expressed, is secreted from a mammalian cell and forms a heptamer or a hexamer, and wherein the pharmaceutical composition induces an immune response when administered to a mammal.
2 . A pharmaceutical composition according to claim 1 , wherein the immunogenic peptide has at least 90% sequence homology to a portion of the Zika virus NS1 protein sequence set forth in SEQ ID NO: 1.
3 . A pharmaceutical composition according to claim 1 , wherein the immunogenic peptide elicits one or more of a T-cell response, T-helper response and/or a cytotoxic-T-cell response and/or a B-cell response.
4 . A pharmaceutical composition according to claim 1 , wherein the immunogenic peptide has at least 90% sequence identity to a portion of the NS1 protein located from position 172 to 352, or from position 172 to 278, or from position 204 to 278, or from position 204 to 352, or from position 204 to 218, or from position 204 to 221, or from positions 207 to 218, or from position 207 to 221, or from position 261 to 275, or from position 261 to 278, or from positions 264 to 275, or from position 264 to 278.
5 . A pharmaceutical composition according to claim 1 , wherein the immunogenic peptide has at least 90%, at least 95%, at least 98%, at least 99% or 100% sequence identity to a portion of the non-structural protein 1 (NS1 protein) of Zika virus, across the length of the immunogenic peptide.
6 . A pharmaceutical composition according to claim 1 , wherein the heterologous signal peptide directs secretion of the immunogenic peptide from a mammalian cell.
7 . A pharmaceutical composition according to claim 1 , wherein the heterologous signal peptide is selected from the group consisting of: tissue plasminogen activator (tPA) signal sequence, erythropoietin (epo) signal sequence, VP22 HSV1 signal sequence, Parathyroid hormone-related protein (PTHrP)N-terminal ER signal, Calreticulin (CRT), Adenovirus E3 signal sequence or a flavivirus signal sequence.
8 . A pharmaceutical composition according to claim 1 , wherein the heterologous signal peptide is a tissue plasminogen activator (tPA) signal peptide.
9 . A pharmaceutical composition according to claim 1 , wherein the heterologous signal peptide is not an immunoglobulin (Ig) signalling peptide, or is not an IgE signalling peptide.
10 . A pharmaceutical composition according to claim 1 , wherein the heterologous signal peptide has 80%, 85%, 90%, 95% or 100% sequence homology to the sequences set forth in SEQ ID NO: 5 or SEQ ID NO: 12.
11 . A pharmaceutical composition according to claim 1 , wherein the nucleic acid molecule includes a sequence which has at least 80%, 85%, 90%, 95%, 98%, 99% or 100% sequence identity to the sequence set forth in SEQ ID NO: 6.
12 . A pharmaceutical composition according to claim 1 , wherein the nucleic acid molecule includes a promoter which is a constitutive promoter in a mammalian cell.
13 . A pharmaceutical composition according to claim 12 , wherein the promoter is a CMV promoter.
14 . A pharmaceutical composition according to claim 1 , wherein the pharmaceutical composition includes:
a DNA vector including the nucleic acid molecule encoding the immunogenic peptide and the operatively linked heterologous signal peptide; or
a viral vector including the nucleic acid molecule encoding the immunogenic peptide and the operatively linked heterologous signal peptide.
15 . A pharmaceutical composition according to claim 14 , wherein the DNA vector is the pVax 1 vector.
16 . A pharmaceutical composition according to claim 1 , wherein the nucleic acid is RNA.
17 . A method of eliciting an immune response in a subject, the method including the step of:
administering to the subject an immunogenic agent, wherein the immunogenic agent is a pharmaceutical composition according to claim 1 .
18 . A method of eliciting an immune response in a subject according to claim 17 , wherein the immune response is a T cell response.
19 . A method of reducing the viral titer in a subject with a Zika virus infection, the method including a step of prophylactically administering to the subject a pharmaceutical composition according to claim 1 .
20 . A pharmaceutical composition comprising a protein encoded by a nucleic acid molecule including an immunogenic peptide comprising a portion of the non-structural protein 1 (NS1 protein) of Zika virus, the nucleic acid further encoding a heterologous signal peptide operatively linked to the immunogenic peptide, wherein the immunogenic peptide, when expressed, is secreted from a mammalian cell and forms a heptamer or a hexamer, and wherein the pharmaceutical composition induces an immune response when administered to a mammal.