FUSION PROTEIN COMPRISING CIRCOVIRIDAE CAPSID PROTEIN, AND CHIMERIC VIRUS-LIKE PARTICLES COMPOSED THEREOF

Abstract

The present invention relates to recombinantly constructed polypeptides useful for preparing vaccines, in particular for reducing one or more clinical signs caused by an infection with at least one pathogen, such as clinical signs caused by a viral infection. More particular, the present invention is directed to a polypeptide comprising a Circoviridae capsid protein linked to a heterologous protein or fragment thereof, and to chimeric virus-like particles composed of such polypeptides. In one example, a fusion protein is provided which comprises PCV2 ORF2 protein linked to an immunogenic fragment of rotavirus VP8 protein, and which is usable for reducing one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection in swine.

Claims

1. A polypeptide comprising a Circoviridae virus capsid protein linked to a heterologous protein or fragment thereof, wherein said heterologous protein or fragment thereof consists of an amino acid sequence being at least 50 amino acid residues in length.

2. A polypeptide, in particular the polypeptide of claim 1, wherein said polypeptide is a fusion protein of the formula x-y-z, wherein x consists of or comprises a Circoviridae virus capsid protein; y is a linker moiety; and z is a heterologous protein or fragment thereof, and/or wherein said heterologous protein or fragment thereof comprises or is an immunogenic fragment of a rotavirus VP8 protein.

3. The polypeptide of claim 1, wherein said Circoviridae virus capsid protein is selected from the group consisting of porcine circovirus type 2 (PCV2) ORF2 protein, bat associated circovirus 2 (BACV2) capsid protein and beak and feather disease virus (BFDV) capsid protein, and/or wherein said Circoviridae virus capsid protein comprises or consists of an amino acid sequence comprising 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:1, SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4.

4. The polypeptide of claim 2, 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 claim 2, 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 claim 2, 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 claim 2, 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 claim 2, wherein said heterologous protein or fragment thereof comprises or consists of an amino acid sequence comprising 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:7, SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10.

9. The polypeptide of claim 2, wherein said linker moiety is an amino acid sequence being 1 to 50 amino acid residues in length, and/or wherein said linker moiety preferably comprises or consists of an amino acid sequence comprising 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:11, SEQ ID NO:12 and SEQ ID NO:13.

10. The polypeptide of claim 2, wherein said polypeptide is a protein comprising or consisting of an amino acid sequence comprising 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:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20 and SEQ ID NO:21.

11. A virus-like particle comprising or composed of a plurality of the polypeptide of claim 1, preferably characterized in that the heterologous protein or fragment thereof is displayed on the exterior surface of the virus-like particle.

12. An immunogenic composition comprising the polypeptide of claim 1 or the virus-like particle of claim 11.

13. A polynucleotide comprising a nucleotide sequence which encodes the polypeptide of claim 1, and wherein said polynucleotide preferably comprises a nucleotide sequence comprising 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:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28 and SEQ ID NO:29.

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

15. The polypeptide of claim 1 or the immunogenic composition of claim 12 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 a rotavirus infection in a subject, and/or for use in a method for inducing an immune response against rotavirus in a subject.

16. The polypeptide of claim 1 or the immunogenic composition of claim 12 for use in a method for inducing an immune response against rotavirus and inducing an immune response against a Circoviridae virus, wherein the Circoviridae virus is preferably of the species encoding said Circoviridae capsid protein, in a subject.

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

18. The polypeptide or the immunogenic composition according to claim 15 or the method of claim 17, 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.

19. The polypeptide or the immunogenic composition according to claim 15, or the method of claim 17, 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.

20. A method of producing the polypeptide of claim 1 or the virus-like particle of claim 11, comprising transfecting a cell with a plasmid comprising a polynucleotide according to claim 13, or infecting a cell, preferably an insect cell, with a baculovirus comprising a polynucleotide according to claim 13.

Description

LIST OF FIGURES

[0262] FIG. 1: Negative-stained electron microscope image of PCV2 ORF2 protein VLPs.

[0263] FIG. 2: Negative-stained electron microscope image of PCV2-CVP8 protein VLPs.

[0264] FIG. 3: Serum IgG response of pigs, either vaccinated with PCV2-AVP8 protein formulated with Emulsigen D (results represented in the line chart by the (upper) line starting at study day −1) or with Placebo (results represented in the line chart by the (bottom) line starting at study day 1).

[0265] FIG. 4: 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 PCV2-AVP8 protein formulated with Emulsigen D (termed “PCV2 ORF2 VLP Carrier AVP8” in the labelling) or with Placebo (“non-relevant vaccine control”).

[0266] FIG. 5: 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 T02, 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).

[0267] FIG. 6: Group median log rotavirus A RNA genomic copies (gc)/mL in feces by study day.

[0268] FIG. 7: Group median anti-PCV2 titer in serum (bar=range) by study day.

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

[0269] SEQ ID NO:1 corresponds to the sequence of a PCV2 ORF2 protein,

[0270] SEQ ID NO:2 corresponds to the sequence of a PCV2 ORF2 protein,

[0271] SEQ ID NO:3 corresponds to the sequence of a BACV2 capsid protein,

[0272] SEQ ID NO:4 corresponds to the sequence of a BFDV capsid protein,

[0273] SEQ ID NO:5 corresponds to the sequence of a (genotype P[7]) rotavirus VP8 protein, sourced from a farm in North Carolina, USA,

[0274] SEQ ID NO:6 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,

[0275] SEQ ID NO:7 corresponds to the sequence of an immunogenic fragment of a (genotype P[7]) rotavirus VP8 protein, sourced from a farm in North Carolina, USA,

[0276] SEQ ID NO:8 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])),

[0277] SEQ ID NO:9 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]),

[0278] SEQ ID NO:10 corresponds to the sequence of an immunogenic fragment of a rotavirus C VP8 protein,

[0279] SEQ ID NO:11 corresponds to the sequence of a linker moiety,

[0280] SEQ ID NO:12 corresponds to the sequence of a linker moiety,

[0281] SEQ ID NO:13 corresponds to the sequence of a linker moiety,

[0282] SEQ ID NO:14 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:1, SEQ ID NO:11, and SEQ ID NO:7,

[0283] SEQ ID NO:15 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:1, SEQ ID NO:11 and SEQ ID NO:8,

[0284] SEQ ID NO:16 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:1, SEQ ID NO:11, and SEQ ID NO:9,

[0285] SEQ ID NO:17 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:3, SEQ ID NO:11 and SEQ ID NO:7,

[0286] SEQ ID NO:18 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:4, SEQ ID NO:11, and SEQ ID NO:7,

[0287] SEQ ID NO:19 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:1, SEQ ID NO:11 and SEQ ID NO:10,

[0288] SEQ ID NO:20 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:3, SEQ ID NO:11 and SEQ ID NO:10,

[0289] SEQ ID NO:21 corresponds to the sequence of a polypeptide (fusion protein) which comprises the sequences of SEQ ID NO:4, SEQ ID NO:11 and SEQ ID NO:10,

[0290] SEQ ID NO:22 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:14,

[0291] SEQ ID NO:23 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:15,

[0292] SEQ ID NO:24 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:16,

[0293] SEQ ID NO:25 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:17,

[0294] SEQ ID NO:26 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:18,

[0295] SEQ ID NO:27 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:19,

[0296] SEQ ID NO:28 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:20,

[0297] SEQ ID NO:29 corresponds to the sequence of a polynucleotide encoding the polypeptide (fusion protein) of SEQ ID NO:21,

[0298] SEQ ID NOs:30-33: primer and probe sequences (Table 3).

[0299] The following clauses are also disclosed herein. Thus, the present disclosure further includes aspects as featured by the following clauses: [0300] 1. A polypeptide comprising a Circoviridae virus capsid protein linked to a heterologous protein or fragment thereof. [0301] 2. The polypeptide of clause 1, wherein the C-terminal amino acid residue of said Circoviridae virus capsid protein is linked to the N-terminal amino acid residue of said heterologous protein or fragment thereof. [0302] 3. The polypeptide of clause 1 or 2, [0303] wherein said Circoviridae virus capsid protein is linked to said heterologous protein or fragment thereof via a linker moiety, [0304] or wherein said Circoviridae virus capsid protein is linked to said heterologous protein or fragment thereof via a peptide bond between the C-terminal amino acid residue of said Circoviridae virus capsid protein and the N-terminal amino acid residue of said heterologous protein or fragment thereof. [0305] 4. The polypeptide of any one of clauses 1 to 3, wherein said polypeptide is a fusion protein. [0306] 5. A polypeptide, in particular the polypeptide of any one of clauses 1 to 4, wherein said polypeptide is a fusion protein of the formula x-y-z, wherein [0307] x consists of or comprises a Circoviridae virus capsid protein; [0308] y is a linker moiety; and [0309] z is a heterologous protein or fragment thereof. [0310] 6. The polypeptide of any one of clauses 1 to 5, wherein said heterologous protein or fragment thereof consists of an amino acid sequence being at least 50 amino acid residues in length, preferably at least 100 amino acid residues in length, most preferably at least 150 amino acid residues in length. [0311] 7. The polypeptide of any one of clauses 1 to 6, wherein said heterologous protein or fragment thereof comprises or consists of an amino acid sequence being 50 to 1000 amino acid residues in length, preferably 100 to 500 amino acid residues in length, most preferably 150 to 250 amino acid residues in length. [0312] 8. The polypeptide of any one of clauses 1 to 7, wherein said heterologous protein or fragment thereof comprises or consists of a protein domain, and wherein said protein domain is preferably at least 50 amino acid residues in length, more preferably at least 100 amino acid residues in length, most preferably at least 150 amino acid residues in length. [0313] 9. The polypeptide of any one of clauses 1 to 8, wherein said heterologous protein or fragment thereof is a non-Circoviridae protein or a fragment thereof and/or wherein said heterologous protein or fragment thereof is a protein or fragment thereof encoded by the genome of a pathogen other than a Circoviridae virus. [0314] 10. The polypeptide of any one of clauses 1 to 9, wherein said heterologous protein or fragment thereof is a protein or fragment thereof encoded by the genome of a virus other than a Circoviridae virus. [0315] 11. The polypeptide of any one of clauses 1 to 10, wherein said Circoviridae virus is selected from the group consisting of porcine circovirus type 2 (PCV2), bat associated circovirus 2 (BACV2) and beak and feather disease virus (BFDV). [0316] 12. The polypeptide of any one of clauses 1 to 11, wherein said Circoviridae virus is PCV2, and wherein said PCV2 is preferably selected from the group consisting of PCV2 subtype a (PCV2a) and PCV2 subtype d (PCV2d). [0317] 13. The polypeptide of any one of clauses 1 to 12, wherein said Circoviridae virus capsid protein is selected from the group consisting of PCV2 ORF2 protein, BACV2 capsid protein and BFDV capsid protein. [0318] 14. The polypeptide of any one of clauses 1 to 13, wherein said Circoviridae virus capsid protein is a PCV2 ORF2 protein, and wherein said PCV2 ORF2 protein is preferably selected from the group consisting of [0319] PCV2 subtype a (PCV2a) ORF2 protein and PCV2 subtype d (PCV2d) ORF2 protein. [0320] 15. The polypeptide of any one of clauses 1 to 14, wherein said Circoviridae virus capsid 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 NO:1, SEQ ID NO:2, SEQ ID NO:3 and SEQ ID NO:4. [0321] 16. The polypeptide of any one of clauses 1 to 15, wherein said heterologous protein or fragment thereof is a rotavirus protein or fragment thereof. [0322] 17. The polypeptide of any one of clauses 1 to 16, wherein said heterologous protein or fragment thereof is a rotavirus VP8 protein or fragment thereof. [0323] 18. The polypeptide of any one of clauses 1 to 17, wherein said heterologous protein or fragment thereof comprises or is an immunogenic fragment of a rotavirus VP8 protein. [0324] 19. The polypeptide of any one of clauses 1 to 18, wherein said heterologous protein or fragment thereof is an immunogenic fragment of a rotavirus VP8 protein. [0325] 20. The polypeptide of clause 18 or 19, 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. [0326] 21. The polypeptide of any one of clauses 18 to 21, wherein said immunogenic fragment of a rotavirus VP8 protein is 50 to 200, preferably 140 to 190 amino acid residues, in length. [0327] 22. The polypeptide of any one of clauses 16 to 21, wherein said rotavirus is porcine rotavirus. [0328] 23. The polypeptide of any one of clauses 16 to 22, wherein said rotavirus is selected from the group consisting of rotavirus A and rotavirus C. [0329] 24. The polypeptide of clause of any one of clauses 16 to 23, wherein said rotavirus is rotavirus A. [0330] 25. The polypeptide of any one of clauses 16 to 24, wherein said immunogenic fragment of a rotavirus VP8 protein comprises the lectin-like domain of a rotavirus VP8 protein. [0331] 26. The polypeptide of any one of clauses 16 to 25, 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. [0332] 27. The polypeptide of clause 25 or 26, 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. [0333] 28. The polypeptide of clause 26 or 27, 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. [0334] 29. The polypeptide of any one of clauses 16 to 28, wherein said immunogenic fragment of a rotavirus VP8 protein consists of the amino acid sequence of [0335] 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, [0336] of a rotavirus VP8 protein. [0337] 30. The polypeptide of any one of clauses 16 to 29, 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. [0338] 31. The polypeptide of any one of clauses 27 to 30, 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 protein is preferably the protein set forth in SEQ ID NO:5. [0339] 32. The polypeptide of any one of clauses 16 to 31, wherein said rotavirus is selected from the group consisting of genotype P[7] rotavirus, genotype P[6] rotavirus and genotype P[13] rotavirus. [0340] 33. The polypeptide of any one of clauses 16 to 32, 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:5. [0341] 34. The polypeptide of any one of clauses 25 to 33, 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:6. [0342] 35. The polypeptide of any one of clauses 16 to 34, 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:7. [0343] 36. The polypeptide of any one of clauses 16 to 35, 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, [0344] and wherein said consensus sequence of a portion of a rotavirus VP8 protein is preferably obtainable by a method comprising the steps of: [0345] translating a plurality of nucleotide sequences encoding a portion of a rotavirus VP8 protein into amino acid sequences, [0346] aligning said amino acid sequences to known rotavirus VP8 proteins, preferably by using MUSCLE sequence alignment software UPGMB clustering and default gap penalty parameters, [0347] 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, [0348] computing the optimal tree using the Poisson correction method with bootstrap test of phylogeny (n=100), [0349] 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, [0350] considering nodes where bootstrap cluster association is greater than 70% as significant, [0351] designating nodes with approximately 10% distance and bootstrap cluster associations greater than 70% as clusters, and [0352] selecting a cluster and generating the consensus sequences by identifying the greatest frequency per aligned position within the cluster, [0353] 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. [0354] 37. The polypeptide of any one of clauses 16 to 36, 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:8 and SEQ ID NO:9. [0355] 38. The polypeptide of any one of clauses 16 to 23, wherein said rotavirus is rotavirus C. [0356] 39. The polypeptide of any one of clauses 16 to 23 and 38, 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:10. [0357] 40. The polypeptide of any one of clauses 1 to 39, wherein said heterologous protein or fragment thereof consists of or is [0358] an immunogenic fragment of a rotavirus A VP8 protein, as specified in any one or more of clauses 24 to 35, or [0359] 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 clause 36 or 37, or [0360] an immunogenic fragment of a rotavirus C VP8 protein, as specified in clause 38 or 39. [0361] 41. The polypeptide of any one of clauses 1 to 40, wherein said heterologous protein or fragment thereof 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 NO:7, SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10. [0362] 42. The polypeptide of any one of clauses 3 to 41, wherein said linker moiety is an amino acid sequence being 1 to 50 amino acid residues in length. [0363] 43. The polypeptide of any one of clauses 3 to 42, 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:11, SEQ ID NO:12 and SEQ ID NO:13. [0364] 44. The polypeptide of any one of clauses 1 to 43, 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:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20 and SEQ ID NO:21. [0365] 45. The polypeptide of any one of clauses 1 to 44, wherein said polypeptide is a recombinant protein, preferably a recombinant baculovirus expressed protein. [0366] 46. The polypeptide of any one of clauses 1 to 45, wherein said polypeptide is capable to assemble with a plurality of the same polypeptide to form a virus-like particle. [0367] 47. The polypeptide of clause 46, wherein the heterologous protein or fragment thereof is displayed on the exterior surface of the virus-like particle. [0368] 48. A virus-like particle comprising or composed of a plurality of the polypeptide of any one of clauses 1 to 47. [0369] 49. The virus-like particle of clause 48, wherein the heterologous protein or fragment thereof is displayed on the exterior surface of the virus-like particle. [0370] 50. An immunogenic composition comprising the polypeptide of any one of clauses 1 to 47 and/or the virus-like particle of clause 48 or 49. [0371] 51. The immunogenic composition of clause 50, wherein the immunogenic composition further comprises a pharmaceutical- or veterinary-acceptable carrier or excipient. [0372] 52. The immunogenic composition of clause 50 or 51, wherein the immunogenic composition further comprises an adjuvant. [0373] 53. An immunogenic composition comprising or consisting of [0374] the polypeptide of any one of clauses 1 to 47 and/or the virus-like particle of clause 48 or 49, and [0375] a pharmaceutical- or veterinary-acceptable carrier or excipient, [0376] and optionally an adjuvant. [0377] 54. The immunogenic composition of clause 52 or 53, wherein the adjuvant is an emulsified oil-in-water adjuvant. [0378] 55. The immunogenic composition of clause 52 or 53, wherein the adjuvant is a carbomer. [0379] 56. A polynucleotide comprising a nucleotide sequence which encodes the polypeptide of any one of clauses 1 to 47, 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:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28 and SEQ ID NO:29. [0380] 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 47. [0381] 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 47. [0382] 60. A baculovirus containing a polynucleotide comprising a sequence which encodes the polypeptide of any one of clauses 1 to 47. [0383] 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 47. [0384] 62. Use of: [0385] the polypeptide of any one of clauses 1 to 47, [0386] the virus-like particle of clause 48 or 49, [0387] the immunogenic composition of any one of clauses 50 to 55, [0388] the polynucleotide of clause 56 or 57, [0389] the plasmid of clause 58, [0390] the cell of clause 59 or 61, [0391] and/or [0392] the baculovirus of clause 60, [0393] for the preparation of a medicament, preferably of a vaccine. [0394] 63. The polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 for use as a medicament. [0395] 64. The polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 for use as a vaccine. [0396] 65. The polypeptide of any one of clauses 1 to 47 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 or disease caused by an infection with a pathogen. [0397] 66. The polypeptide or the immunogenic composition according to clause 65, wherein the pathogen is a pathogen of the species having a genome encoding said heterologous protein or fragment thereof. [0398] 67. The polypeptide of any one of clauses 1 to 47 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 a rotavirus infection in a subject. [0399] 68. The polypeptide of any one of clauses 1 to 47 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. [0400] 69. The polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 for use in a method for [0401] inducing an immune response against a pathogen of the species having a genome encoding the heterologous protein or fragment thereof [0402] and [0403] inducing an immune response against a Circoviridae virus, wherein the Circoviridae virus is preferably of the species encoding said Circoviridae capsid protein, [0404] in a subject. [0405] 70. The polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 for use in a method for inducing an immune response against rotavirus and PCV2 in a subject. [0406] 71. The polypeptide or the immunogenic composition according to any one of clauses 67 to 70, wherein the subject is a mammal or a bird, and wherein the bird is preferably a chicken. [0407] 72. The polypeptide or the immunogenic composition according to any one of clauses 67 to 71, wherein the subject is a mammal, and wherein the mammal is preferably a swine or a bovine. [0408] 73. The polypeptide or the immunogenic composition according to any one of clauses 67 to 72, wherein the subject is a pig, and wherein the pig is preferably a piglet or a sow. [0409] 74. The polypeptide or the immunogenic composition according to clause 67, wherein the subject is a piglet. [0410] 75. The polypeptide or the immunogenic composition according to any one of clause 68 to 70, wherein the subject is a pregnant sow. [0411] 76. The polypeptide of any one of clauses 1 to 47 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. [0412] 77. The polypeptide or the immunogenic composition according to clause 76, 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. [0413] 78. The polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 for use in a method of reducing or preventing [0414] one or more clinical signs caused by an infection with a pathogen of the species having a genome encoding the heterologous protein or fragment thereof [0415] and [0416] one or more clinical signs caused by an infection with a Circoviridae virus, wherein the Circoviridae virus is preferably of the species encoding said Circoviridae capsid protein.

[0417] 79. The polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 for use in a method of reducing or preventing [0418] one or more clinical signs, mortality or fecal shedding caused by a rotavirus infection, [0419] and [0420] one or more clinical signs, mortality or nasal shedding caused by PCV2. [0421] 80. 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 47 or the immunogenic composition of any one of clauses 50 to 55 to a subject. [0422] 81. 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 47 or the immunogenic composition of any one of clauses 50 to 55 to said sow. [0423] 82. A method of reducing or preventing one ore more clinical signs, mortality or fecal shedding caused by an infection with a rotavirus in a piglet, wherein said method comprises [0424] administering the polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 to a sow, and [0425] allowing said piglet to be suckled by said sow. [0426] 83. The method of clause 82, wherein said sow is a sow being pregnant, in particular with said piglet. [0427] 84. The method of clause 82 or 83, comprising the steps of [0428] administering the polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 to a sow being pregnant with said piglet, [0429] allowing said sow to give birth to said piglet, and [0430] allowing said piglet to be suckled by said sow. [0431] 85. 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 polypeptide of any one of clauses 1 to 47 or the immunogenic composition of any one of clauses 50 to 55 has been administered. [0432] 86. The polypeptide or the immunogenic composition according to any one of clauses 65 to 79 or the method of any one of clauses 80 to 85, wherein said one or more clinical signs are selected from the group consisting of [0433] diarrhea, [0434] pathogen colonization, in particular colonization of the pathogen of the species having a genome encoding the heterologous protein or fragment thereof, wherein said pathogen colonization is preferably rotavirus colonization, [0435] lesions, in particular macroscopic lesions, [0436] decreased average daily weight gain, and [0437] gastroenteritis. [0438] 87. The polypeptide or the immunogenic composition according to clause 86 or the method of clause 86, wherein said pathogen colonization is a rotavirus colonization of the intestine and/or wherein said lesions are enteric lesions. [0439] 88. The polypeptide or the immunogenic composition according to any one of clauses 65 to 79, 86 and 87, or the method of any one of clauses 80 to 87, wherein [0440] said rotavirus infection is an infection with genotype P[23] rotavirus and/or genotype P[7] rotavirus, [0441] said infection with a rotavirus is an infection with a genotype P[23] rotavirus and/or genotype P[7] rotavirus, [0442] said immune response against rotavirus is an immune response against genotype P[23] rotavirus and/or genotype P[7] rotavirus, or [0443] said antibodies specific for rotavirus are antibodies specific for genotype P[23] rotavirus and/or genotype P[7] rotavirus. [0444] 89. The polypeptide according to clause 88, wherein said polypeptide is the polypeptide of any one of clauses 1 to 37 and 40 to 47, characterized in that said fragment of said heterologous protein is an immunogenic fragment of a genotype P[7] rotavirus VP8 protein. [0445] 90. The immunogenic composition according to clause 88, wherein the immunogenic composition comprises a polypeptide of any one of clauses 1 to 37 and 40 to 47, characterized in that said fragment of said heterologous protein is an immunogenic fragment of a genotype P[7] rotavirus VP8 protein. [0446] 91. The method according to clause 88, wherein [0447] the polypeptide of any one of clauses 1 to 37 and 40 to 47, characterized in that said fragment of said heterologous protein is an immunogenic fragment of a genotype P[7] rotavirus VP8 protein, or [0448] an immunogenic composition comprising the polypeptide of any one of clauses 1 to 37 and 40 to 47, characterized in that said fragment of said heterologous protein is an immunogenic fragment of a genotype P[7] rotavirus VP8 protein, [0449] is administered or has been administered. [0450] 92. The polypeptide according to clause 89, the immunogenic composition according to clause 90, or the method according to clause 91, wherein [0451] said fragment 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:7, and/or [0452] 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:14. [0453] 93. A method of producing the polypeptide of any one of clauses 1 to 47 and/or the virus-like particle of clause 48 or 49, comprising transfecting a cell with the plasmid of clause 58. [0454] 94. A method of producing the polypeptide of any one of clauses 1 to 47 and/or the virus-like particle of clause 48 or 49, comprising infecting a cell, preferably an insect cell, with the baculovirus of clause 60.