Vaccine for preventing and treating Merkel cell carcinoma
The present invention provides a novel vaccine for preventing and treating Merkel cell carcinoma. The present invention constructs a therapeutic vaccine based on a Merkel cell polyomavirus capsid protein VP1 by taking the Merkel cell polyomavirus capsid protein VP1 as an antigen, in combination with a TLR agonist. The present invention effectively solves the problem of prevention and treatment of the Merkel cell carcinoma and has great application value and application prospects.
1 . A vaccine composition against Merkel cell carcinoma comprising: (a) Merkel cell polyomavirus capsid protein VP1 or a nucleic acid comprising a nucleotide sequence encoding the Merkel cell polyomavirus capsid protein VP1; and (b) a TLR agonist comprising one or more of CpG, R848, and MPL;
wherein the nucleotide sequence encoding the Merkel cell polyomavirus capsid protein VP1 is 71.9%-74.7% identical to SEQ ID No. 6.
2 . The vaccine composition according to claim 1 , wherein the TLR agonist is a combination of CpG and R848.
3 . The vaccine composition according to claim 1 , wherein the vaccine composition further comprises an aluminum-based adjuvant.
4 . The vaccine composition according to claim 3 , wherein the vaccine composition comprises 5-500 parts by weight of the Merkel cell polyomavirus capsid protein VP1 or the nucleic acid encoding the Merkel cell polyomavirus capsid protein VP1, 2.5-250 parts by weight of the TLR agonist, and 10-1000 parts by weight of the aluminum-based adjuvant.
5 . The vaccine composition according to claim 4 , wherein the vaccine composition comprises 10-100 parts by weight of the Merkel cell polyomavirus capsid protein VP1 or the nucleic acid encoding the Merkel cell polyomavirus capsid protein VP1, 5-100 parts by weight of the TLR agonist, and 50-500 parts by weight of the aluminum-based adjuvant.
6 . The vaccine composition according to claim 1 , wherein the nucleotide sequence encoding the Merkel cell polyomavirus capsid protein VP1 is set forth in SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, or SEQ ID No. 4.
7 . A nucleic acid encoding Merkel cell polyomavirus capsid protein VP1, wherein the nucleic acid comprising a nucleotide sequence 71.9%-74.7% identical to SEQ ID No. 6; and wherein the nucleotide sequence encodes the VP1.
8 . The nucleic acid according to claim 7 , wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, or SEQ ID No. 4.
9 . A method for preparing a vaccine composition against Merkel cell carcinoma, the method comprising mixing the nucleic acid according to claim 7 or the VP1 protein encoded thereby with an adjuvant to form the vaccine composition.
10 . The method according to claim 9 , wherein the nucleic acid comprises the nucleotide sequence set forth in SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, or SEQ ID No. 4.
11 . A vaccine composition against Merkel cell carcinoma, wherein the vaccine composition comprises the nucleic acid according to claim 7 , or the VP1 protein encoded thereby.
12 . The vaccine composition according to claim 11 , wherein the vaccine composition comprises the nucleic acid comprising the nucleotide sequence set forth in SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, or SEQ ID No. 4, or the VP1 protein encoded thereby.
13 . The vaccine according to claim 12 , wherein the vaccine composition further comprises an adjuvant comprising a TLR agonist and an aluminum-based adjuvant, the TLR agonist being one or more of CpG, R848, and MPL.
14 . A method for treating or reducing the risk for Merkel cell carcinoma in a subject, the method comprising administering to a subject in need thereof the vaccine composition according to claim 11 .
15 . The method according to claim 14 , wherein the vaccine composition comprises the nucleic acid comprising the nucleotide sequence set forth in SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3, or SEQ ID No. 4, or the VP1 protein encoded thereby.
16 . The method according to claim 14 , wherein the vaccine composition further comprises an adjuvant comprising a TLR agonist and an aluminum-based adjuvant, and wherein the TLR agonist comprises one or more of CpG, R848, and MPL.
17 . The method according to claim 14 , wherein the subject has Merkel cell carcinoma or is at risk for developing Merkel cell carcinoma.
18 . The vaccine composition of claim 1 , wherein the nucleic acid is a DNA plasmid.
19 . The nucleic acid of claim 7 , which is a DNA plasmid.
20 . The vaccine composition of claim 11 , wherein the nucleic acid is a DNA plasmid.