FUSION PROTEIN USEFUL FOR VACCINATION AGAINST ROTAVIRUS

Abstract

The present invention relates to recombinantly constructed polypeptides useful for preparing vaccines, in particular for reducing one or more clinical signs caused by a rotavirus infection. More particular, the present invention is directed to a fusion protein comprising in N- to C-terminal direction (i) an immunogenic fragment of a rotavirus VP8 protein and (ii) an immunoglobulin Fc fragment such as, for example, an IgG Fc fragment, wherein said fusion protein is usable in a method of reducing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in swine.

Claims

1. A polypeptide comprising an immunogenic fragment of a rotavirus VP8 protein, and an immunoglobulin Fc fragment.

2. The polypeptide of claim 1, wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein via a linker moiety, or wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein via a peptide bond between the N-terminal amino acid residue of said immunoglobulin Fc fragment and the C-terminal amino acid residue of said immunogenic fragment of a rotavirus VP8 protein.

3. A polypeptide, in particular the polypeptide of claim 1 or 2, wherein said polypeptide is a fusion protein of the formula x-y-z, wherein x consists of an immunogenic fragment of a rotavirus VP8 protein; y is a linker moiety; and z is an immunoglobulin Fc fragment.

4. The polypeptide of any one of claims 1 to 3, wherein said rotavirus is porcine rotavirus, and/or wherein said rotavirus is selected from the group consisting of rotavirus A and rotavirus C.

5. The polypeptide of any one of claims 1 to 4, wherein said immunogenic fragment of a rotavirus VP8 protein is an N-terminally extended lectin-like domain of a rotavirus VP8 protein, wherein the N-terminal extension is 1 to 20 amino acid residues, preferably 5 to 15 amino acid residues, in length.

6. The polypeptide of any one of claims 1 to 5, wherein said rotavirus is selected from the group consisting of genotype P[7] rotavirus, genotype P[6] rotavirus and genotype P[13] rotavirus.

7. The polypeptide of any one of claims 1 to 6, wherein the immunogenic fragment of a rotavirus VP8 protein consists of or is a consensus sequence of a portion of a rotavirus VP8 protein, in particular of a portion of a rotavirus A VP8 protein, and wherein said consensus sequence of a portion of a rotavirus VP8 protein is preferably obtainable by a method comprising the steps of: translating a plurality of nucleotide sequences encoding a portion of a rotavirus VP8 protein into amino acid sequences, aligning said amino acid sequences to known rotavirus VP8 proteins, preferably by using MUSCLE sequence alignment software UPGMB clustering and default gap penalty parameters, subjecting said aligned sequences to a phylogenetic analysis and generating a neighbor joining phylogeny reconstruction based on rotavirus VP8 protein sequence, in particular importing said aligned amino acid sequences into MEGA7 software for phylogenetic analysis and generating a neighbor joining phylogeny reconstruction based on rotavirus VP8 protein sequence, computing the optimal tree using the Poisson correction method with bootstrap test of phylogeny (n=100), drawing the optimal tree to scale with branch lengths equal to evolutionary distances in units of amino acid substitutions per site over 170 total positions, considering nodes where bootstrap cluster association is greater than 70% as significant, designating nodes with approximately 10% distance and bootstrap cluster associations greater than 70% as clusters, and selecting a cluster and generating the consensus sequences by identifying the greatest frequency per aligned position within the cluster, and optionally, in cases where equivalent proportions of amino acids are observed in an aligned position, selecting the amino acid residue based on reported epidemiological data in conjunction with a predefined product protection profile.

8. The polypeptide of any one of claims 1 to 7, wherein the immunogenic fragment of a rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with a sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6.

9. The polypeptide of any one of claims 1 to 8, wherein said immunoglobulin Fc fragment is an immunoglobulin Fc fragment encoded by the genome of a species whose intestinal cells are susceptible to an infection by the rotavirus from which the immunogenic fragment of a rotavirus VP8 protein is derived, and/or wherein said immunoglobulin Fc fragment is preferably a swine IgG Fc fragment, and/or wherein said immunoglobulin Fc fragment comprises or consists of an amino acid sequence having at least 70%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:7 and SEQ ID NO:8.

10. The polypeptide of any one of claims 1 to 9, wherein said linker moiety is an amino acid sequence being 1 to 50 amino acid residues in length, and/or wherein said linker moiety comprises or consists of an amino acid sequence having at least 66%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11.

11. The polypeptide of any one of claims 2 to 10, wherein said polypeptide comprises a further immunogenic fragment of a rotavirus VP8 protein linked to the C-terminus of said immunoglobulin Fc fragment, wherein said further immunogenic fragment of a rotavirus VP8 protein is preferably linked to the C-terminus of said immunoglobulin Fc fragment via a linker moiety, wherein said linker moiety is in particular a linker moiety as specified in claim 10, or wherein said further immunogenic fragment of a rotavirus VP8 protein is linked to the C-terminus of said immunoglobulin Fc fragment via a peptide bond between the N-terminal amino acid residue of said further immunogenic fragment of a rotavirus VP8 protein and the C-terminal amino acid residue of said immunoglobulin Fc fragment, and wherein said further immunogenic fragment of a rotavirus VP8 protein preferably comprises or consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with a sequence selected from the group consisting of SEQ ID NOs: 2 to 6, and/or wherein said further immunogenic fragment of a rotavirus VP8 protein is preferably different from the immunogenic fragment of a rotavirus VP8 protein of which the C-terminus is linked to said immunoglobulin Fc fragment.

12. The polypeptide of any one of claims 1 to 11, wherein said polypeptide is a protein comprising or consisting of an amino acid sequence having at least 70%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15 and SEQ ID NO:16.

13. A multimer comprising or composed of a plurality of the polypeptide of any one of claims 1 to 12, and wherein said multimer is preferably a homodimer formed by a polypeptide of any one of claims 1 to 12 with a second identical polypeptide.

14. An immunogenic composition comprising the polypeptide of any one of claims 1 to 12 and/or the multimer of claim 13.

15. A polynucleotide comprising a nucleotide sequence which encodes the polypeptide of any one of claims 1 to 12, and wherein said polynucleotide preferably comprises a nucleotide sequence having at least 70%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20 and SEQ ID NO:21.

16. The polypeptide of any one of claims 1 to 12 or the immunogenic composition of claim 14 for use as a medicament, preferably for use as a vaccine.

17. The polypeptide of any one of claims 1 to 12 or the immunogenic composition of claim 14 for use in a method of reducing or preventing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in a subject or for use in a method of treating or preventing an infection with rotavirus in a subject or for use in a method of treating or preventing an infection with rotavirus in a subject, and/or for use in a method for inducing an immune response against rotavirus in a subject.

18. A method of reducing or preventing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in a piglet, wherein said method comprises administering the polypeptide of any one of claims 1 to 12 or the immunogenic composition of claim 14 to a sow, and allowing said piglet to be suckled by said sow.

19. The polypeptide or the immunogenic composition according to claim 17, or the method of claim 18, wherein said one or more clinical signs are selected from the group consisting of diarrhea, rotavirus colonization, in particular rotavirus colonization of the intestine, lesions, in particular macroscopic lesions, decreased average daily weight gain, and gastroenteritis.

20. The polypeptide or the immunogenic composition according to claim 17 or 19, or the method of claim 18 or 19, wherein said rotavirus infection is an infection with genotype P[23] rotavirus and/or genotype P[7] rotavirus, said infection with a rotavirus is an infection with a genotype P[23] rotavirus and/or genotype P[7] rotavirus, or said immune response against rotavirus is an immune response against genotype P[23] rotavirus and/or genotype P[7] rotavirus.

21. The polypeptide or the immunogenic composition according to claim 20, or the method of claim 20, wherein said polypeptide comprises an immunogenic fragment of a genotype P[7] rotavirus VP 8 protein, or wherein said immunogenic composition comprises a polypeptide comprising an immunogenic fragment of a genotype P[7] rotavirus VP8 protein, and wherein preferably said immunogenic fragment of a genotype P[7] rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with the sequence of SEQ ID NO:3.

22. A method of producing the immunogenic composition of claim 14, wherein the method comprises the steps of: (a) permitting infection of susceptible cells in culture with a vector comprising a nucleic acid sequence encoding a polypeptide of any one of claims 1 to 12, wherein said polypeptide is expressed by said vector; (b) thereafter recovering said polypeptide, in particular in the cell culture supernatant, wherein preferably cell debris is separated from said polypeptide via a separation step, preferably including a micro filtration through at least one filter, preferably two filters, wherein the at least one filter preferably has a pore size of about 1 to about 20 μm and/or about 0.1 μm to about 4 μm; (c) inactivating the vector by adding binary ethylenimine (BEI) to the mixture of step (b); (d) neutralizing the BEI by adding sodium thiosulfate to the mixture resulting from step (c); and (e) concentrating the polypeptide in the mixture resulting from step (d) by removing a portion of the liquid from the mixture by a filtration step utilizing a filter with a filter membrane having a molecular weight cut off of between about 5 kDa and about 100 kDa, preferably between about 10 kDa and about 50 kDa; (f) and optionally admixing the mixture remaining after step (e) with a further component selected from the group consisting of pharmaceutically acceptable carriers, adjuvants, diluents, excipients, and combinations thereof.

Description

LIST OF FIGURES

[0302] FIG. 1: Serum IgG response of pigs, either vaccinated with AVP8-IgG Fc protein formulated with Emulsigen D (termed “AVP8-IgG” in the labelling) or with Placebo (“Non-relevant control”), directed against porcine rotavirus A.

[0303] FIG. 2: Results of a VN (virus neutralization) assay conducted for detecting and quantifying antibodies being capable to neutralize porcine rotavirus A virus, in samples of pigs vaccinated with AVP8-IgG Fc protein formulated with Emulsigen D (termed “AVP8-IgG” in the labelling) or with Placebo (“Non-relevant control”).

[0304] FIG. 3: Mean VN titers against rotavirus in sow serum by group and study day, wherein study days D0 and D28 represent the time points “six weeks and two weeks pre-farrow” (i.e. when investigational products were administered to study group T02 and T04, respectively) and study days D7, D28 and D35 represent the time points “five weeks, two weeks and one week pre-farrow” (i.e. when Commercial vaccine was administered to T06).

[0305] FIG. 4: Group median log rotavirus A RNA genomic copies (gc)/mL in feces by study day.

[0306] FIG. 5: A) SDS-PAGE of protein A purified AVP8-IgG Fc protein (SEQ ID NO:12) product samples being either reduced with Dithiothreitol (“+DTT”) or non-reduced (“−DTT”); B) Western Blot of AVP8-IgG Fc protein (SEQ ID NO:12) bioreactor product, wherein a sample was centrifuged to separate a cell pellet fraction (“Pellet”) and a supernatant fraction (“Supernatant”), which after a freeze-thaw process were run out on SDS-PAGE under reducing conditions (+DTT), transferred to a PVDF membrane and probed with HRP conjugated goat anti-swine to detect swine IgG Fc fragment.

[0307] FIG. 6: Mean VN titers against rotavirus in sow serum by group and study day, wherein study days D0 and D28 represent the time points “six weeks and two weeks pre-farrow” (i.e. when investigational products were administered to study group T01 and T03, respectively).

IN THE SEQUENCE LISTING/SOURCE AND GEOGRAPHICAL ORIGIN (WHERE APPLICABLE)

[0308] SEQ ID NO:1 corresponds to the sequence of a (genotype P[7]) rotavirus VP8 protein, sourced from a farm in North Carolina, USA,

[0309] SEQ ID NO:2 corresponds to the sequence of a lectin-like domain of a (genotype P[7]) rotavirus VP8 protein, sourced from a farm in North Carolina, USA,

[0310] SEQ ID NO:3 corresponds to the sequence of an immunogenic fragment of a (genotype P[7]) rotavirus VP8 protein, sourced from a farm in North Carolina, USA,

[0311] SEQ ID NO:4 corresponds to the sequence of an immunogenic fragment of a rotavirus VP8 protein, i.e. a consensus sequence of a portion of rotavirus VP8 protein (based on genotype P[6])),

[0312] SEQ ID NO:5 corresponds to the sequence of an immunogenic fragment of a rotavirus VP8 protein, i.e. a consensus sequence of a portion of consensus sequence of an immunogenic fragment of rotavirus VP8 protein (based on genotype P[13]),

[0313] SEQ ID NO:6 corresponds to the sequence of an immunogenic fragment of a rotavirus C VP8 protein,

[0314] SEQ ID NO:7 corresponds to the sequence of a swine IgG Fc fragment,

[0315] SEQ ID NO:8 corresponds to the sequence of a guinea pig IgG Fc fragment,

[0316] SEQ ID NO:9 corresponds to the sequence of a linker moiety,

[0317] SEQ ID NO:10 corresponds to the sequence of a linker moiety,

[0318] SEQ ID NO:11 corresponds to the sequence of a linker moiety,

[0319] SEQ ID NO:12 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:3, SEQ ID NO:9, and SEQ ID NO:7,

[0320] SEQ ID NO:13 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:4, SEQ ID NO:9, and SEQ ID NO:7,

[0321] SEQ ID NO:14 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:5, SEQ ID NO:9, and SEQ ID NO:7,

[0322] SEQ ID NO:15 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:6, SEQ ID NO:9, and SEQ ID NO:7,

[0323] SEQ ID NO:16 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:3, SEQ ID NO:9, SEQ ID NO:7, SEQ ID NO:10, and SEQ ID NO:5,

[0324] SEQ ID NO:17 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:12,

[0325] SEQ ID NO:18 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:13,

[0326] SEQ ID NO:19 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:14,

[0327] SEQ ID NO:20 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:15,

[0328] SEQ ID NO:21 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:16,

[0329] SEQ ID NOs:22-25: primer and probe sequences (Table 5).

[0330] The following clauses are also disclosed herein. Thus, the present disclosure further includes aspects as featured by the following clauses: [0331] 1. A polypeptide comprising [0332] an immunogenic fragment of a rotavirus VP8 protein, and [0333] an immunoglobulin Fc fragment. [0334] 2. The polypeptide of clause 1, wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein, [0335] or wherein said immunoglobulin Fc fragment is linked to the N-terminus of said immunogenic fragment of a rotavirus VP8 protein. [0336] 3. The polypeptide of clause 1 or 2, wherein [0337] said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein via a linker moiety, [0338] or wherein said immunoglobulin Fc fragment is linked to the N-terminus of said immunogenic fragment of a rotavirus VP8 protein via a linker moiety. [0339] 4. The polypeptide of any one of clauses 1 to 3, wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein via a peptide bond between the N-terminal amino acid residue of said immunoglobulin Fc fragment and the C-terminal amino acid residue of said immunogenic fragment of a rotavirus VP8 protein, [0340] or wherein said immunoglobulin Fc fragment is linked to the N-terminus of said immunogenic fragment of a rotavirus VP8 protein via a peptide bond between the C-terminal amino acid residue of said immunoglobulin Fc fragment and the N-terminal amino acid residue of said immunogenic fragment of a rotavirus VP8 protein. [0341] 5. The polypeptide of any one of clauses 1 to 4, wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein. [0342] 6. The polypeptide of any one of clauses 1 to 5, wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein via a linker moiety, [0343] or wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein via a peptide bond between the N-terminal amino acid residue of said immunoglobulin Fc fragment and the C-terminal amino acid residue of said immunogenic fragment of a rotavirus VP8 protein. [0344] 7. The polypeptide of any one of clauses 1 to 6, wherein said polypeptide is a fusion protein. [0345] 8. A polypeptide, in particular the polypeptide of any one of clauses 1 to 7, wherein said polypeptide is a fusion protein of the formula x-y-z, wherein [0346] x consists of an immunogenic fragment of a rotavirus VP8 protein; [0347] y is a linker moiety; and [0348] z is an immunoglobulin Fc fragment. [0349] 9. The polypeptide of any one of clauses 1 to 8, wherein said immunogenic fragment of a rotavirus VP8 protein is capable of inducing an immune response against rotavirus in a subject to whom said immunogenic fragment of a rotavirus VP8 protein is administered. [0350] 10. The polypeptide of any one of clauses 1 to 9, wherein said immunogenic fragment of a rotavirus VP8 protein is 50 to 200, preferably 140 to 190 amino acid residues, in length. [0351] 11. The polypeptide of any one of clauses 1 to 10, wherein said rotavirus is porcine rotavirus. [0352] 12. The polypeptide of any one of clauses 1 to 11, wherein said rotavirus is selected from the group consisting of rotavirus A and rotavirus C. [0353] 13. The polypeptide of any one of clauses 1 to 12, wherein said rotavirus is rotavirus A. [0354] 14. The polypeptide of any one of clauses 1 to 13, wherein said immunogenic fragment of a rotavirus VP8 protein comprises the lectin-like domain of a rotavirus VP8 protein. [0355] 15. The polypeptide of any one of clauses 1 to 14, wherein said immunogenic fragment of a rotavirus VP8 protein is an N-terminally extended lectin-like domain of a rotavirus VP8 protein, wherein the N-terminal extension is 1 to 20 amino acid residues, preferably 5 to 15 amino acid residues, in length. [0356] 16. The polypeptide of clause 14 or 15, wherein the lectin-like domain of a rotavirus VP8 protein consists of the amino acid sequence of the amino acid residues 65-224 of a rotavirus VP8 protein. [0357] 17. The polypeptide of clause 15 or 16, wherein the amino acid sequence of said N-terminal extension is the amino acid sequence of the respective length flanking the N-terminal amino acid residue of the lectin-like domain in the amino acid sequence of the rotavirus VP8 protein. [0358] 18. The polypeptide of any one of clauses 1 to 17, wherein said immunogenic fragment of a rotavirus VP8 protein consists of the amino acid sequence of [0359] the amino acid residues 60-224, the amino acid residues 59-224, the amino acid residues 58-224, the amino acid residues 57-224, the amino acid residues 56-224, the amino acid residues 55-224, the amino acid residues 54-224, the amino acid residues 53-224, the amino acid residues 52-224, the amino acid residues 51-224, the amino acid residues 50-224, or the amino residues 49-224, [0360] of a rotavirus VP8 protein. [0361] 19. The polypeptide of any one of clauses 1 to 18, wherein said immunogenic fragment of a rotavirus VP8 protein consists of the amino acid sequence of the amino acid residues 57-224 of a rotavirus VP8 protein. [0362] 20. The polypeptide of any one of clauses 16 to 19, wherein the numbering of said amino acid residues refers to the amino acid sequence of a wild-type rotavirus VP8 protein, in particular of a wild-type rotavirus A VP8 protein, and wherein said wild-type rotavirus VP8 is preferably the protein set forth in SEQ ID NO:1. [0363] 21. The polypeptide of any one of clauses 1 to 20, wherein said rotavirus is selected from the group consisting of genotype P[7] rotavirus, genotype P[6] rotavirus and genotype P[13] rotavirus. [0364] 22. The polypeptide of any one of clauses 1 to 21, wherein the rotavirus VP8 protein comprises or consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with the sequence of SEQ ID NO:1. [0365] 23. The polypeptide of any one of clauses 14 to 22, wherein the lectin-like domain of a rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with the sequence of SEQ ID NO:2. [0366] 24. The polypeptide of any one of clauses 1 to 23, wherein the immunogenic fragment of a rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with the sequence of SEQ ID NO:3. [0367] 25. The polypeptide of any one of clauses 1 to 24, wherein the immunogenic fragment of a rotavirus VP8 protein consists of or is a consensus sequence of a portion of a rotavirus VP8 protein, in particular of a portion of a rotavirus A VP8 protein, and wherein said consensus sequence of a portion of a rotavirus VP8 protein is preferably obtainable by a method comprising the steps of: [0368] translating a plurality of nucleotide sequences encoding a portion of a rotavirus VP8 protein into amino acid sequences, [0369] aligning said amino acid sequences to known rotavirus VP8 proteins, preferably by using MUSCLE sequence alignment software UPGMB clustering and default gap penalty parameters, [0370] subjecting said aligned sequences to a phylogenetic analysis and generating a neighbor joining phylogeny reconstruction based on rotavirus VP8 protein sequence, in particular importing said aligned amino acid sequences into MEGA7 software for phylogenetic analysis and generating a neighbor joining phylogeny reconstruction based on rotavirus VP8 protein sequence, [0371] computing the optimal tree using the Poisson correction method with bootstrap test of phylogeny (n=100), [0372] drawing the optimal tree to scale with branch lengths equal to evolutionary distances in units of amino acid substitutions per site over 170 total positions, [0373] considering nodes where bootstrap cluster association is greater than 70% as significant, [0374] designating nodes with approximately 10% distance and bootstrap cluster associations greater than 70% as clusters, and [0375] selecting a cluster and generating the consensus sequences by identifying the greatest frequency per aligned position within the cluster, [0376] and optionally, in cases where equivalent proportions of amino acids are observed in an aligned position, selecting the amino acid residue based on reported epidemiological data in conjunction with a predefined product protection profile. [0377] 26. The polypeptide of any one of clauses 1 to 25, wherein the immunogenic fragment of a rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with a sequence selected from the group consisting of SEQ 4 and SEQ ID NO:5. [0378] 27. The polypeptide of any one of clauses 1 to 26, wherein said rotavirus is rotavirus C. [0379] 28. The polypeptide of clause 1 to 27, wherein the immunogenic fragment of a rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with the sequence of SEQ ID NO:6. [0380] 29. The polypeptide of any one of clauses 1 to 28, wherein said immunogenic fragment of a rotavirus VP8 protein consists of or is [0381] an immunogenic fragment of a rotavirus A VP8 protein, as specified in any one or more of clauses 9 to 24, or [0382] a consensus sequence of a portion of a rotavirus VP8 protein, in particular of a portion of a rotavirus A VP8 protein, as specified in any one of clauses 9 to 13, 25 and 26, or [0383] an immunogenic fragment of a rotavirus C VP8 protein, as specified in any one of clauses 9 to 12, 27 and 28. [0384] 30. The polypeptide of any one of clauses 1 to 29, wherein the immunogenic fragment of a rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with a sequence selected from the group consisting of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 and SEQ ID NO:6. [0385] 31. The polypeptide of any one of clauses 1 to 30, [0386] wherein said immunoglobulin Fc fragment is at least 220 amino acid residues in length, preferably 220 to 250 amino acid residues in length, [0387] and/or wherein the immunoglobulin Fc fragment is non-glycosylated. [0388] 32. The polypeptide of any one of clauses 1 to 31, wherein said immunoglobulin Fc fragment comprises or consists of the heavy-chain constant region 2 (CH2) and the heavy-chain constant region 3 (CH3), and optionally the hinge region or a part of the hinge region, of an immunoglobulin. [0389] 33. The polypeptide of any one of clauses 1 to 32, wherein said immunoglobulin is selected from the group consisting of IgG, IgA, IgD, IgE and IgM. [0390] 34. The polypeptide of any one of clauses 1 to 33, wherein said immunoglobulin Fc fragment is an immunoglobulin Fc fragment encoded by the genome of a species whose intestinal cells are susceptible to an infection by the rotavirus from which the immunogenic fragment of a rotavirus VP8 protein is derived. [0391] 35. The polypeptide of any one of clauses 1 to 34, wherein said immunoglobulin Fc fragment is a swine IgG Fc fragment. [0392] 36. The polypeptide of any one of clauses 1 to 35, wherein said immunoglobulin Fc fragment comprises or consists of an amino acid sequence having at least 70%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:7 and SEQ ID NO:8. [0393] 37. The polypeptide of any one of clauses 3 to 36, wherein said linker moiety is an amino acid sequence being 1 to 50 amino acid residues in length. [0394] 38. The polypeptide of any one of clauses 3 to 37, wherein said linker moiety comprises or consists of an amino acid sequence having at least 66%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:9, SEQ ID NO:10 and SEQ ID NO:11. [0395] 39. The polypeptide of any one of clauses 5 to 38, wherein said polypeptide has an N-terminal methionine residue flanking the N-terminal amino acid residue of said immunogenic fragment of a rotavirus VP8 protein. [0396] 40. The polypeptide of any one of clauses 5 to 39, wherein said polypeptide comprises a further immunogenic fragment of a rotavirus VP8 protein linked to the C-terminus of said immunoglobulin Fc fragment. [0397] 41. A polypeptide, in particular the polypeptide of any one of clauses 1 to 40, comprising [0398] an immunogenic fragment (1) of a rotavirus VP8 protein, [0399] an immunoglobulin Fc fragment, and [0400] a further immunogenic fragment (2) of a rotavirus VP8 protein, [0401] wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment (1), [0402] and wherein said further immunogenic fragment (2) of a rotavirus VP8 protein is linked to the C-terminus of said immunoglobulin Fc fragment. [0403] 42. The polypeptide of clause 40 or 41, wherein said further immunogenic fragment of a rotavirus VP8 protein consists of or is [0404] an immunogenic fragment of a rotavirus A VP8 protein, as specified in any one or more of clauses 9 to 24; or [0405] a consensus sequence of a portion of a rotavirus VP8 protein, in particular of a portion of a rotavirus A VP8 protein, as specified in any one or more of clauses 9 to 13, 25 and 26; or [0406] an immunogenic fragment of a rotavirus C VP8 protein, as specified in any one or more of clauses 9 to 12, 27 and 28. [0407] 43. The polypeptide of any one of clauses 40 to 42, wherein said further immunogenic fragment of a rotavirus VP8 protein comprises or consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with a sequence selected from the group consisting of SEQ ID NOs: 2 to 6, [0408] and/or wherein said further immunogenic fragment of a rotavirus VP8 protein is different from the immunogenic fragment of a rotavirus VP8 protein of which the C-terminus is linked to said immunoglobulin Fc fragment. [0409] 44. The polypeptide of any one of clauses 40 to 43, [0410] wherein said further immunogenic fragment of a rotavirus VP8 protein is linked to the C-terminus of said immunoglobulin Fc fragment via a linker moiety, wherein said linker moiety is preferably a linker moiety as specified in clause 37 or 38, [0411] or wherein said further immunogenic fragment of a rotavirus VP8 protein is linked to the C-terminus of said immunoglobulin Fc fragment via a peptide bond between the N-terminal amino acid residue of said further immunogenic fragment of a rotavirus VP8 protein and the C-terminal amino acid residue of said immunoglobulin Fc fragment. [0412] 45. The polypeptide of any one of clauses 1 to 44, wherein said polypeptide consists of: [0413] an immunogenic fragment of a rotavirus VP8 protein, in particular an immunogenic fragment of a rotavirus VP8 protein as specified in any one or more of clauses 9 to 30, [0414] an N-terminal methionine residue flanking the N-terminal amino acid residue of said immunogenic fragment of a rotavirus VP8 protein, and [0415] an immunoglobulin Fc fragment, in particular an immunoglobulin Fc fragment as specified in any one or more of clauses 31 to 36, [0416] wherein said immunoglobulin Fc fragment is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein, in particular via a linker moiety, wherein said linker moiety is preferably a linker moiety as specified in clause 37 or 38, [0417] and optionally a further immunogenic fragment of a rotavirus VP8 protein linked to the C-terminus of said immunoglobulin Fc fragment, in particular via a linker moiety, wherein said further immunogenic fragment of a rotavirus VP8 protein is preferably the further immunogenic fragment as specified in any one or more of clauses 41 to 44, and wherein said linker moiety is preferably a linker moiety as specified in clause 37 or 38. [0418] 46. The polypeptide of any one of clauses 1 to 45, wherein said polypeptide is a protein comprising or consisting of an amino acid sequence having at least 70%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15 and SEQ ID NO:16. [0419] 47. The polypeptide of any one of clauses 1 to 46, wherein said polypeptide is a recombinant protein, in particular a recombinant baculovirus expressed protein. [0420] 48. The polypeptide of any one of clauses 1 to 47, wherein said polypeptide forms a homodimer with a second identical polypeptide. [0421] 49. A multimer comprising or composed of a plurality of the polypeptide of any one of clauses 1 to 48, and wherein said multimer is preferably a homodimer formed by a polypeptide of any one of clauses 1 to 48 with a second identical polypeptide. [0422] 50. An immunogenic composition comprising the polypeptide of any one of clauses 1 to 48 and/or the multimer of clause 49. [0423] 51. The immunogenic composition of clause 50, wherein the immunogenic composition further comprises a pharmaceutical- or veterinary-acceptable carrier or excipient. [0424] 52. The immunogenic composition of clause 50 or 51, wherein the immunogenic composition further comprises an adjuvant. [0425] 53. An immunogenic composition comprising or consisting of [0426] the polypeptide of any one of clauses 1 to 48 and/or the multimer of clause 49, and [0427] a pharmaceutical- or veterinary-acceptable carrier or excipient, [0428] and optionally an adjuvant. [0429] 54. The immunogenic composition of clause 52 or 53, wherein the adjuvant is an emulsified oil-in-water adjuvant. [0430] 55. The immunogenic composition of clause 52 or 53, wherein the adjuvant is a carbomer. [0431] 56. A polynucleotide comprising a nucleotide sequence which encodes the polypeptide of any one of clauses 1 to 48, [0432] 57. The polynucleotide of clause 56, wherein said polynucleotide comprises a nucleotide sequence having at least 70%, preferably at least 80%, more preferably at least 90%, still more preferably at least 95% or in particular 100% sequence identity with a sequence selected from the group consisting of SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20 and SEQ ID NO:21. [0433] 58. A plasmid, preferably an expression vector, which comprises a polynucleotide comprising a sequence which encodes the polypeptide of any one of clauses 1 to 48. [0434] 59. A cell comprising a plasmid, preferably an expression vector, which comprises a polynucleotide comprising a sequence which encodes the polypeptide of any one of clauses 1 to 48. [0435] 60. A baculovirus containing a polynucleotide comprising a sequence which encodes the polypeptide of any one of clauses 1 to 48. [0436] 61. A cell, preferably an insect cell, comprising a baculovirus which contains a polynucleotide comprising a sequence which encodes the polypeptide of any one of clauses 1 to 48. [0437] 62. Use of: [0438] the polypeptide of any one of clauses 1 to 48, [0439] the multimer of clause 49, [0440] the immunogenic composition of any one of clauses 50 to 55, [0441] the polynucleotide of clause 56 or 57, [0442] the plasmid of clause 58, [0443] the baculovirus of clause 60, and/or [0444] the cell of clause 59 or 61 [0445] for the preparation of a medicament, preferably of a vaccine. [0446] 63. The polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 for use as a medicament. [0447] 64. The polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 for use as a vaccine. [0448] 65. The polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 for use in a method for inducing an immune response against rotavirus in a subject. [0449] 66. The polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 for use in a method of reducing or preventing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in a subject or for use in a method of treating or preventing an infection with rotavirus in a subject. [0450] 67. The polypeptide or the immunogenic composition according to clause 65 or 66, wherein the subject is a mammal or a bird, and wherein the bird is preferably a chicken. [0451] 68. The polypeptide or the immunogenic composition according to any one of clauses 65 to 67, wherein the subject is a mammal, and wherein the mammal is preferably a swine or a bovine. [0452] 69. The polypeptide or the immunogenic composition according to any one of clauses 65 to 68, wherein the subject is a pig, and wherein the pig is preferably a piglet or a sow. [0453] 70. The polypeptide or the immunogenic composition according to clause 65, wherein the subject is a pregnant sow. [0454] 71. The polypeptide or the immunogenic composition according to clause 66, wherein the subject is a piglet. [0455] 72. The polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 for use in a method of reducing or preventing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in a piglet, wherein the piglet is to be suckled by a sow to which the immunogenic composition has been administered. [0456] 73. The polypeptide or the immunogenic composition according to clause 72, wherein said sow to which the immunogenic composition has been administered is a sow to which the immunogenic composition has been administered while said sow has been pregnant, in particular with said piglet. [0457] 74. A method for the treatment or prevention of a rotavirus infection, the reduction, prevention or treatment of one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection, or the prevention or treatment of a disease caused by a rotavirus infection, comprising administering the polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 to a subject. [0458] 75. A method for inducing the production of antibodies specific for rotavirus in a sow, wherein said method comprises administering the polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 to said sow. [0459] 76. A method of reducing or preventing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in a piglet, wherein said method comprises [0460] administering the polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 to a sow, and [0461] allowing said piglet to be suckled by said sow. [0462] 77. The method of clause 76, wherein said sow is a sow being pregnant, in particular with said piglet. [0463] 78. The method of clause 76 or 77, comprising the steps of [0464] administering the polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 to a sow being pregnant with said piglet, [0465] allowing said sow to give birth to said piglet, and [0466] allowing said piglet to be suckled by said sow. [0467] 79. A method of reducing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in a piglet, wherein the piglet is to be suckled by a sow to which the polypeptide of any one of clauses 1 to 48 or the immunogenic composition of any one of clauses 50 to 55 has been administered. [0468] 80. The polypeptide or the immunogenic composition according to any one of clauses 66 to 73 or the method of any one of clauses 74 to 79, wherein said one or more clinical signs are selected from the group consisting of [0469] diarrhea, [0470] rotavirus colonization, [0471] lesions, in particular macroscopic lesions, [0472] decreased average daily weight gain, and [0473] gastroenteritis. [0474] 81. The polypeptide or the immunogenic composition according to clause 80 or the method of clause 80, wherein said rotavirus colonization is a rotavirus colonization of the intestine and/or wherein said lesions are enteric lesions. [0475] 82. The polypeptide or the immunogenic composition according to any one of clauses 65 to 73, 80 and 81, or the method of any one of clauses 74 to 81, wherein [0476] said rotavirus infection is an infection with genotype P[23] rotavirus and/or genotype P[7] rotavirus, [0477] said infection with a rotavirus is an infection with a genotype P[23] rotavirus and/or genotype P[7] rotavirus, [0478] said immune response against rotavirus is an immune response against genotype P[23] rotavirus and/or genotype P[7] rotavirus, or [0479] said antibodies specific for rotavirus are antibodies specific for genotype P[23] rotavirus and/or genotype P[7] rotavirus. [0480] 83. The polypeptide according to clause 82, wherein said polypeptide comprises an immunogenic fragment of a genotype P[7] rotavirus VP 8 protein, and wherein said polypeptide is preferably the polypeptide as specified in any one of clauses 21 to 26 and 29 to 48. [0481] 84. The immunogenic composition or the method according to clause 82, wherein the immunogenic composition comprises a polypeptide as specified in any one of clauses 21 to 26 and 29 to 48, wherein said immunogenic fragment of a rotavirus VP8 protein is an immunogenic fragment of a genotype P[7] rotavirus VP8 protein. [0482] 85. The polypeptide of clause 83, or the immunogenic composition or the method according to clause 84, wherein said immunogenic fragment of a genotype P[7] rotavirus VP8 protein consists of an amino acid sequence having at least 90%, preferably at least 95%, more preferably at least 98% or still more preferably at least 99% sequence identity with the sequence of SEQ ID NO:3. [0483] 86. A method of producing the polypeptide of any one of clauses 1 to 48 and/or the multimer of clause 49, comprising transfecting a cell with the plasmid of clause 58. [0484] 87. A method of producing the polypeptide of any one of clauses 1 to 48 and/or the multimer of clause 49, comprising infecting a cell, preferably an insect cell, with the baculovirus of clause 60. [0485] 88. A method of producing the immunogenic composition of any one of clauses 50 to 55, wherein the method comprises the steps of: [0486] (a) permitting infection of susceptible cells in culture with a vector comprising a nucleic acid sequence encoding a polypeptide of any one of clauses 1 to 48, wherein said polypeptide is expressed by said vector; [0487] (b) thereafter recovering said polypeptide, in particular in the cell culture supernatant, wherein preferably cell debris is separated from said polypeptide via a separation step, preferably including a micro filtration through at least one filter, preferably two filters, wherein the at least one filter preferably has a pore size of about 1 to about 20 μm and/or about 0.1 μm to about 4 μm; [0488] (c) inactivating the vector by adding binary ethylenimine (BEI) to the mixture of step (b); [0489] (d) neutralizing the BEI by adding sodium thiosulfate to the mixture resulting from step (c); and [0490] (e) concentrating the polypeptide in the mixture resulting from step (d) by removing a portion of the liquid from the mixture by a filtration step utilizing a filter with a filter membrane having a molecular weight cut off of between about 5 kDa and about 100 kDa, preferably between about 10 kDa and about 50 kDa; [0491] (f) and optionally admixing the mixture remaining after step (e) with a further component selected from the group consisting of pharmaceutically acceptable carriers, adjuvants, diluents, excipients, and combinations thereof. [0492] 89. The immunogenic composition according to any one of clauses 50 to 55, 63 to 73 and 80 to 85, the use of clause 62, or the method of any one of clauses 74 to 82, 84 and 85, wherein the immunogenic composition is obtainable by the method of clause 88. [0493] 90. A polypeptide comprising [0494] an immunogenic fragment of a rotavirus VP8 protein, and [0495] a heterologous dimerization domain, [0496] wherein said heterologous dimerization domain is linked to the C-terminus of said immunogenic fragment of a rotavirus VP8 protein. [0497] 91. The polypeptide of clause 90, wherein said heterologous dimerization domain is a coiled-coil domain, in particular a leucine zipper.