Toxoplasma gondii vaccines and their use
Disclosed herein are polynucleotides encoding multi-epitope polypeptides and assemblies thereof, and their use for treating or limiting Toxoplasma gondii infection.
1. An isolated polynucleotide encoding a chimeric polypeptide, wherein the chimeric polypeptide comprises the amino acid sequence
(SEQ ID NO: 24)
AVVSLLRLLKNAMLTAFFLRNAAAKSFKDILPKKAAASSAYVFSVKKA
AAKFVAAWTLKAAAKSTFWPCLLR.
2. The isolated polynucleotide of claim 1 , wherein the chimeric polypeptide further comprises a further peptide domain comprising a peptide capable of promoting self-assembly/multimerization of the polypeptide.
3. The isolated polynucleotide of claim 2 , wherein the further peptide domain comprises the sequence selected from the group consisting of:
(SEQ ID NO: 25)
WEEWNARWDEWENDWNDWREDWQAWRDDWARWRATWM;
(SEQ ID NO: 26)
RLLSRLERLERRNEELRRLLQLIRHENRMVLQFVRALSMQNAELERR
LEEL;
or both.
4. The isolated polynucleotide of claim 2 , wherein the chimeric polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NOS: 27-28 wherein residues in parentheses are optional and may be present or absent.
A11 (residues in parentheses are optional)
(SEQ ID NO: 27)
((MGDKHHHHHHHHHH))KDGSDKGSWEEWNARWDEWENDWNDWREDW
QAWRDDWARWRATWMGGRLLSRLERLERRNEELRRLLQLIRHENRMVL
QFVRALSMQNAELERRLEELARGMAQVINTNSLSLLTQNNLNRSQSAL
GTAIERLSSGLRINSARDDAAGQAIANRFTANIRGLTQASRNANDGIS
IAQTTEGALNEINNNLQRVRELAVQSANSTNSQSDLDSIQAEITQRLN
EIDRVSGQTQFNGVRVLAQDNTLTIQVGANDGETIDIDLRQINSQTLG
LDQLNVQQEYESDD AVVSLLRLLK NAMLTAFFLRNAAAKSFKDILPKK
AAA SSAYVFSVK KAA AKFVAAWTLKAAA KSTFWPCLLRDSDSDTENPL
QRIDAALAQVDALRSDLGAVQNRFNSAITNLGNTVNNLSEARSRIEDS
DYATEVSNMSRAQILQQAGTSVLAQANQVPQNVLSLLR
Tox-all (residues in parentheses are optional)
(SEQ ID NO: 28)
(MGDDHHHHHHHHHH)
WFMGVLVNSLQDITMGSLFFVQDFMIVSISLVQDGLAAAVVAVQDLPQ
FATAATRDSPASGRYIQQMLDQRCQEIAAELCQSGLRKMCVPSSRIVA
RNAVGITHQNTLQWRCFDTASLLESNQENNGVNCVDDCGHTIPCPGGV
HRQNSNHATRHEILSKLVEEGVQRFCSPYQASANKYCNDKFPGTIARR
SKGFGNNVEVAWRCYEKASLLYSVYAECASNCGTTWYCPGGRRGTSTE
LDKRHYTEEEGIRQAIGSVDSPCSEVEVCLPKDENPPLCLDESGQISR
GSWEEWNARWDEWENDWNDWREDWQAWRDDWARWRATWMGGRLLSRLE
RLERRNEELRRLLQLIRHENRMVLQFVRALSMQNAELERRLEELARGM
AQVINTNSLSLLTQNNLNRSQSALGTAIERLSSGLRINSARDDAAGQA
IANRFTANIRGLTQASRNANDGISIAQTTEGALNEINNNLQRVRELAV
QSANSTNSQSDLDSIQAEITQRLNEIDRVSGQTQFNGVRVLAQDNTLT
IQVGANDGETIDIDLRQINSQTLGLDQLNVQQEYESDDAVVSLLRLLK
NAMLTAFFLRNAAAKSFKDILPKKAAASSAYVFSVKKAAAKFVAAWTL
KAAAKSTFWPCLLRDSDSDTENPLQRIDAALAQVDALRSDLGAVQNRF
NSAITNLGNTVNNLSEARSRIEDSDYATEVSNMSRAQILQQAGTSVLA
QANQVPQNVLSLLR.
5. The isolated polynucleotide of claim 1 , wherein the chimeric polypeptide further comprises a secretory signal.
6. The isolated polynucleotide of claim 5 , wherein the secretory signal is present at the N-terminus of the chimeric polypeptide.
7. A recombinant expression vector, comprising the isolated polynucleotide of claim 1 operatively linked to a control sequence.
8. A pharmaceutical composition, comprising:
(a) the isolated polynucleotide encoding a chimeric polypeptide of claim 1 ; and
(b) a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , wherein the composition comprises an adjuvant.