Immunization against sars-cov-related diseases
AssigneeISA Pharmaceuticals B.V.
InventorsCornelis Johannes Maria Melief, Thomas Johannes Maria Beenakker, Peter van Rijn, Anna-Sophia Wiekmeijer, Miranda Bernardina Johanna Molenaar, Leonard Willem Frederik Hooftman
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Abstract
The invention provides long immunogenic peptides for treating diseases related to severe acute respiratory syndrome coronaviruses, such as SARS-CoV-2 or SARS-CoV-1. The invention also provides immunogenic compositions and vaccines comprises long immunogenic peptides of the invention and method of therapeutic treatment or prevention of SARS-CoV-related diseases comprising administration of immunogenic peptides according to the invention.
Claims27
An immunogenic peptide comprising a fragment of a SARS-CoV protein, wherein said fragment is 20-40 amino acids in length and wherein said fragment comprises one or more of the sequences set forth in:
- o) the amino acid sequence LSPRWYFYY (SEQ ID NO:73) and one or more or all of the amino acid sequences:
- DLSPRWYFY (SEQ ID NO:202), DLSPRWYFYY (SEQ ID NO:203), GTGPEAGL (SEQ ID NO:204), MKDLSPRWYFY (SEQ ID NO:205), KDLSPRWYFY (SEQ ID NO:206), LSPRWYFYYL (SEQ ID NO:207), YLGTGPEA (SEQ ID NO:208), KMKDLSPRW (SEQ ID NO:209), KDLSPRWYFYY (SEQ ID NO:210), KMKDLSPRWY (SEQ ID NO:211), KMKDLSPRWYF (SEQ ID NO:212), KDLSPRWYF (SEQ ID NO:213) and SPRWYFYYLGT (SEQ ID NO:214),
- i) the amino acid sequence ALNTLVKQL (SEQ ID NO:52) (S protein),
- ii) the amino acid sequence VLNDILSRL (SEQ ID NO:53) (S protein),
- iii) the amino acid sequence LITGRLQSL (SEQ ID NO:54) (S protein),
- iv) the amino acid sequence QLIRAAEIRASANLAATK (SEQ ID NO:55) (S protein),
- v) the amino acid sequence RLNEVAKNL (SEQ ID NO:56) (S protein),
- vi) the amino acid sequence FIAGLIAIV (SEQ ID NO:57) (S protein),
- vii) the amino acid sequence AYRFNGIGVTQNVLY (SEQ ID NO:58) (S protein),
- viii) the amino acid sequence FLPFFSNVTWF (SEQ ID NO:59) (S protein),
- ix) the amino acid sequence LLALHRSYL (SEQ ID NO:60) (S protein),
- x) the amino acid sequence VRFPNITNL (SEQ ID NO:61) (S protein),
- xi) the amino acid sequence IYQTSNFRVQ (SEQ ID NO:62) (S protein),
- xii) the amino acid sequence SIIAYTMSLG (SEQ ID NO:63) (S protein),
- xiii) the amino acid sequence IVNNATNVVIK (SEQ ID NO:64) (S protein),
- xiv) the amino acid sequence LPNNTASW (SEQ ID NO:65) (N protein),
- xv) the amino acid sequence ALNTPKDHI (SEQ ID NO:66) (N protein),
- xvi) the amino acid sequence LQLPQGTTL (SEQ ID NO:67) (N protein),
- xvii) the amino acid sequence LALLLLDRLNQL (SEQ ID NO:68) (N protein),
- xviii) the amino acid sequence GMSRIGMEV (SEQ ID NO:69) (N protein),
- xix) the amino acid sequence FTALTQHGK (SEQ ID NO:70) (N protein),
- xx) the amino acid sequence FPRGQGVPI (SEQ ID NO:71) (N protein),
- xxi) the amino acid sequence YYRRATRRIRG (SEQ ID NO:72) (N protein),
- xxii) the amino acid sequence LSPRWYFYY (SEQ ID NO:73) (N protein),
- xxiii) the amino acid sequence LALLLLDRLNQL (SEQ ID NO:74) (N protein),
- xxiv) the amino acid sequence GMSRIGMEV (SEQ ID NO:75) (N protein),
- xxv) the amino acid sequence ILLNKHID (SEQ ID NO:76) (N protein),
- xxvi) the amino acid sequence KTFPPTEPK (SEQ ID NO:77) (N protein),
- xxvii) the amino acid sequence NVTQAFGRRGP (SEQ ID NO:78) (N protein),
- xxviii) the amino acid sequence KHWPQIAQFA (SEQ ID NO:79) (N protein),
- xxix) the amino acid sequence TLACFVLAAV (SEQ ID NO:80) (M protein),
- xxx) the amino acid sequence SFNPETNIL (SEQ ID NO:81) (M protein),
- xxxi) the amino acid sequence TVATSRTLSY (SEQ ID NO:82) (M protein),
- xxxii) the amino acid sequence IAWNSNNLDSK (SEQ ID NO:83) (RBD),
- xxxiii) the amino acid sequence SKVGGNYNYLYRLFR (SEQ ID NO:84) (RBD),
- xxxiv) the amino acid sequence CNGVEGFNC (SEQ ID NO:85) (RBD),
- xxxv) the amino acid sequence NCYFPLQSYGFQPTNGVGY (SEQ ID NO:86) (RBD),
- xxxvi) the amino acid sequence GNYNYLYRLFRKSNL (SEQ ID NO:87) (RBD),
- xxxvii) the amino acid sequence set forth in SEQ ID NO:325 (S protein),
- xxxviii) the amino acid sequence set forth in SEQ ID NO:331 (RBD), or
- xxxix) the amino acid sequence set forth in SEQ ID NO:340 (RBD).
A vaccine product comprising one or more immunogenic compositions, wherein the one or more immunogenic compositions comprise the peptides set forth in:
- SEQ ID NO:19 and SEQ ID NO:38, or
- SEQ ID NO:19 and SEQ ID NO:323, or
- SEQ ID NO:38 and SEQ ID NO:323, or
- SEQ ID NO:19, SEQ ID NO:38 and SEQ ID NO:323, or
- two, three or all of SEQ ID NO:19, 22, 38 and 323, or
- two, three, four, five, six or all of:
- SEQ ID NO:9, 12, 19, 32, 33, 37 and 38, or
- two, three, four, five, six or all of:
- SEQ ID NO:326, 12, 19, 32, 33, 37 and 38, or
- two, three, four, five, six or all of:
- SEQ ID NO:9, 12, 19, 325, 33, 37 and 38, or
- two, three, four, five, six or all of:
- SEQ ID NO:9, 12, 19, 32, 33, 328 and 38, or
- two, three, four, five, six or all of:
- SEQ ID NO:9, 340, 19, 32, 33, 37 and 38, or
- two, three, four, five, six, seven or all of:
- SEQ ID NO:9, 12, 19, 32, 33, 37, 38 and 323, or
- two, three, four, five, six, seven or all of:
- SEQ ID NO:326, 12, 19, 32, 33, 37, 38 and 323, or
- two, three, four, five, six, seven or all of:
- SEQ ID NO:9, 12, 19, 325, 33, 37, 38 and 323, or
- two, three, four, five, six, seven or all of:
- SEQ ID NO:9, 12, 19, 32, 33, 328, 38 and 323, or
- two, three, four, five, six, seven or all of:
- SEQ ID NO:9, 340, 19, 32, 33, 37, 38 and 323, or
- two, three, four, five, six, seven, eight, nine or all of:
- SEQ ID NO:9, 12, 19, 22, 32, 33, 37, 38, 39 and 40, or
- two, three, four, five, six, seven, eight, nine or all of:
- SEQ ID NO:326, 12, 19, 22, 32, 33, 37, 38, 39 and 40, or
- two, three, four, five, six, seven, eight, nine or all of:
- SEQ ID NO:9, 12, 19, 22, 325, 33, 37, 38, 39 and 40, or
- two, three, four, five, six, seven, eight, nine or all of:
- SEQ ID NO:9, 12, 19, 22, 32, 33, 328, 38, 39 and 40, or
- two, three, four, five, six, seven, eight, nine or all of:
- SEQ ID NO:9, 340, 19, 22, 32, 33, 37, 38, 39 and 40, or
- two, three, four, five, six, seven, eight, nine, ten or all of:
- SEQ ID NO:9, 12, 19, 22, 32, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten or all of:
- SEQ ID NO:326, 12, 19, 22, 32, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten or all of:
- SEQ ID NO:9, 12, 19, 22, 325, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten or all of:
- SEQ ID NO:9, 12, 19, 22, 32, 33, 328, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten or all of:
- SEQ ID NO:9, 340, 19, 22, 32, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or all of:
- SEQ ID NO:
- 9, 10, 12, 15, 19, 22, 32, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or all of:
- SEQ ID NO:
- 326, 327, 12, 330, 19, 22, 32, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or all of:
- SEQ ID NO:
- 9, 10, 12, 331, 19, 22, 325, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or all of:
- SEQ ID NO:
- 9, 10, 12, 331, 19, 22, 32, 33, 328, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or all of:
- SEQ ID NO:
- 9, 10, 340, 15, 19, 22, 32, 33, 37, 38, 39, 40 and 323, or
- two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or all of:
- SEQ ID NO:
- 5, 9, 10, 12, 15, 17, 19, 22, 24, 29, 30, 32, 33, 36, 37, 38, 39, 40, 44, 45 and 323, or
- two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, sixteen, seventeen, eighteen, nineteen, twenty or all of:
- SEQ ID NO:
- 5, 9, 10, 340, 15, 342, 19, 22, 24, 343, 30, 32, 33, 36, 37, 38, 39, 40, 44, 45 and 323, or
- two, three, four, five or all of:
- SEQ ID NO:9, 19, 32, 33, 38 and 39, or
- two, three, four, five or all of:
- SEQ ID NO:326, 19, 32, 33, 38 and 39, or
- two, three, four, five or all of:
- SEQ ID NO:9, 19, 325, 33, 38 and 39.
A method for selecting a peptide sequence for use in immunization against a SARS-CoV-related disease, comprising the steps of:
- a) identify S, N and/or M variant protein sequences of a variant SARS-CoV strain circulating in the human population,
- b) compare the reference peptide sequences described in any one of the preceding claims with the corresponding variant protein sequences, identify amino acid sequence differences and design a variant peptide sequence incorporating said amino acid difference(s),
- c) analyze the effect of said amino acid sequence differences on predicted ligands by:
- i) determining predicted ligand counts per HLA super-type for the reference peptide sequence in the variant background and for the variant peptide sequence in the variant background,
- ii) assessing whether there is an increased total number of predicted ligands when using the variant peptide sequence in the variant background as compared to the number obtained with reference peptide sequence in the variant background,
- d) select the variant peptide sequence for use in immunization if an increased number of predicted ligands is obtained in step c) ii).
Dependencies are inferred from the claim text.