VACCINE COMPOSITIONS CONTAINING MODIFIED ZIKA VIRUS ANTIGENS
The present disclosure relates to vaccine compositions that comprise a Zika virus antigen and an adjuvant. The present disclosure also provides methods for inducing a protective immune response by administering the disclosed vaccine compositions in a subject in needs thereof. The present methods also comprise the binding of the Zika virus vaccine to Zika virus cellular receptor proteins.
1 . A Zika virus polypeptide comprising
(a) an EnvD polypeptide, wherein the EnvD polypeptide comprises or consists of a polypeptide having at least 90% identity to SEQ ID NO:8; and, optionally,
(b) a heterologous amino acid portion C-terminal to the E80 polypeptide.
2 . The Zika virus polypeptide of claim 1 wherein the heterologous amino acid portion comprises a protease cleavage site.
3 . The Zika virus polypeptide of claim 2 wherein the protease cleavage site is selected from a group of sites cleaved by TEV protease, pepsin A, thermoylsin, furin, proteinase K, thrombin and trypsin.
4 . The Zika virus polypeptide of claim 3 wherein the protease cleavage site is cleaved by TEV protease.
5 . The Zika virus polypeptide of claim 1 wherein the heterologous amino acid portion comprises a tag.
6 . The Zika virus polypeptide of claim 4 wherein the tag is selected from the group consisting of a FLAG-tag, a polyHis-tag, a Myc-tag, a Glutathione-S-transferase-tag, a Green fluorescent protein-tag, and a maltose binding protein-tag.
7 . The Zika virus polypeptide of claim 6 wherein the tag is a polyhistidine tag and the tag is located C-terminal to the EnvD polypeptide.
8 . The Zika virus polypeptide of claim 1 wherein the heterologous amino acid portion comprises the residual portion of a protease cleavage site and does not comprise a tag.
9 . The Zika virus polypeptide of claim 1 wherein the EnvD polypeptide comprises an N-terminal PrM polypeptide having at least 90% identity to SEQ ID NO:9.
10 . An immunogenic composition comprising the Zika virus polypeptide of claim 1 , and a pharmaceutically acceptable carrier.
11 . The immunogenic composition of claim 10 comprising dimeric polypeptides and wherein the dimer comprises dimer-specific epitopes.
12 . The immunogenic composition of claim 10 wherein the composition comprises an adjuvant present in an amount effective to enhance the immune response to the Zika virus polypeptide.
13 . The immunogenic composition of claim 12 , wherein the adjuvant is selected from the group consisting of a mineral compound-based adjuvant, a bacterial adjuvant, an oil-based emulsion, an immunostimulatory complex (ISCOM), and a synthetic adjuvant.
14 . The immunogenic composition of claim 12 , wherein the adjuvant is Matrix-M1™ adjuvant.
15 . A method of inducing an immune response comprising administering the composition of claim 10 to a subject.
16 . The method of claim 15 wherein the subject is a human male or a female.
17 . The method of claim 15 wherein the immune response comprises anti-Zika antibodies.
18 . The method of claim 17 wherein the anti-Zika antibodies comprise a dimer-specific antibody.
19 . The composition of claim 10 comprising
(a) a Zika polypeptide dimer, wherein the dimer contains two Zika virus polypeptides according to claim 1 ;
(b) about 20 mM to about 40 mM NaPO4, pH 7.2 to 7.5;
(c) about 200 mM to about 400 mM NaCl;
(d) about 0.02% to about 0.05% of a surfactant; and
(e) about 750 μM to about 1.5 mM EDTA.
20 . The composition of claim 19 comprising
(a) a Zika polypeptide dimer, wherein the dimer contains two Zika virus polypeptides according to claim 1 ;
(b) about 25 mM NaPO4, pH 7.5;
(c) about 300 mM NaCl;
(d) about 0.03% PS20; and
(e) about 1 mM EDTA;
21 . The composition of claim 10 wherein dimer stability, as determined by SPR using an anti-dimer antibody, is maintained at about 90% after 4 weeks storage at 4° C.