Polyvalent chimeric rubella virus-based vaccines
A chimeric viral particle that comprises a RV fusion gene is disclosed. The RV fusion gene comprises a first nucleotide sequence encoding a RV that is devoid of RV E1 protein, and a second nucleotide sequence that linked in translation frame to the first nucleotide sequence and encodes a humoral immunogenic viral protein. The chimeric viral particle is free of RV E1 protein-encoding gene. A virus packaging cell that generates the chimeric viral particle comprising a RV fusion gene and an isolated expression vector comprising a RV fusion gene linked in translation frame to a promoter are also disclosed.
1. A chimeric viral particle whose genome comprises:
a) a first nucleotide sequence encoding rubella virus (RV) proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of RV E1 protein; and
b) a second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encoding respiratory syncytial virus (RSV) F protein;
wherein the chimeric viral particle is free of RV E1 protein-encoding gene.
2. The chimeric viral particle of claim 1 , further comprising:
c) a third nucleotide sequence, linked in translation frame to the first or the second nucleotide sequence, encoding hemaagglutinin-neuramindase (HN) of human Parainfluenza Virus Type 3 (hPIV-3).
3. The chimeric viral particle of claim 1 , wherein the first nucleotide sequence comprises:
i) a first polynucleotide sequence encoding RV nonstructural proteins;
ii) a second polynucleotide sequence encoding RV capsid (C) protein; and
iii) a third polynucleotide sequence encoding RV E2 protein.
4. A viral vaccine comprising a nontoxic, physiologically acceptable carrier and an immunogenic amount of the chimeric viral particle of claim 1 .
5. A viral vaccine comprising a nontoxic, physiologically acceptable carrier and an immunogenic amount of the chimeric viral particle of claim 2 .
6. A virus packaging cell which generates the chimeric viral particle of claim 1 , wherein the virus packaging cell's genome comprises:
a) a nucleotide sequence encoding RV structural proteins C, E2 and E1; and
b) an expression vector comprising:
i) a promoter;
ii) a first nucleotide sequence, linked in translation frame to the promoter, encoding RV proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of RV E1 protein; and
iii) a second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encoding RSV F protein;
wherein the expression vector is devoid of RV E1 protein-encoding nucleotide sequence.
7. A virus packaging cell which generates the chimeric viral particle of claim 2 , wherein the virus packaging cell's genome comprises:
a) a nucleotide sequence encoding RV structural proteins C, E2 and E1; and
b) an expression vector comprising:
i) a promoter;
ii) a first nucleotide sequence, linked in translation frame to the promoter, encoding RV proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of E1 protein;
iii) a second nucleotide sequence, linked in translation frame with the first nucleotide sequence, encoding respiratory syncytial virus (RSV) F protein; and
iv) a third nucleotide sequence, linked in translation frame to the first or the second nucleotide sequence, encoding hemaagglutinin-neuramindase (HN) of human Parainfluenza Virus Type 3 (hPIV-3);
wherein the expression vector is devoid of RV E1 protein-encoding nucleotide sequence.
8. A method of eliciting a humoral immune response against RV and RSV in a mammal, comprising administering to the mammal the viral vaccine of claim 4 , thereby eliciting the humoral immune response against RV and RSV in the mammal.
9. A method of eliciting a humoral immune response against RV, RSV and hPIV-3 in a mammal, comprising administering to the mammal the viral vaccine of claim 5 , thereby eliciting the humoral immune response against RV, RSV and hPIV-3 in the mammal.
10. A chimeric viral particle whose genome comprises:
a) a first nucleotide sequence encoding RV proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of RV E1 protein; and
b) a second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encoding an immunogenic foreign viral protein;
wherein the chimeric viral particle is free of RV E1 protein-encoding gene.
11. The chimeric viral particle of claim 10 , wherein the second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encodes hemaagglutinin-neuramindase (HN) of human Parainfluenza Virus Type 3 ihPIV-3).
12. The chimeric viral particle of claim 11 , whose genome further comprises:
c) a third nucleotide sequence, linked in translation frame to the second nucleotide sequence, encoding RSV F protein.
13. A viral vaccine comprising a nontoxic, physiologically acceptable carrier and an immunogenic amount of the chimeric viral particle of claim 11 .
14. A viral vaccine comprising a nontoxic, physiologically acceptable carrier and an immunogenic amount of the chimeric viral particle of claim 12 .
15. A virus packaging cell which generates the chimeric viral particle of claim 11 , wherein the virus packaging cell's genome comprises:
a) a nucleotide sequence encoding RV structural proteins C, E2 and E1; and
b) an expression vector comprising:
i) a promoter;
ii) a first nucleotide sequence, linked in translation frame to the promoter, encoding RV proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of E1 protein; and
iii) a second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encoding hemaagglutinin-neuramindase (HN) of human Parainfluenza Virus Type 3 (hPIV-3);
wherein the expression vector is devoid of RV E1 protein-encoding nucleotide sequence.
16. A virus packaging cell which generates the chimeric viral particle of claim 12 , wherein the virus packaging cell's genome comprises:
a) a nucleotide sequence encoding RV structural proteins C, E2 and E1; and
b) an expression vector comprising
i) a promoter;
ii) a first nucleotide sequence, linked in translation frame to the promoter, encoding RV proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of E1 protein;
iii) a second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encoding hemaagglutinin-neuramindase (HN) of human Parainfluenza Virus Type 3 (hPIV-3); and
iv) a third nucleotide sequence, linked in translation frame to the second nucleotide sequence, encoding RSV F protein;
wherein the expression vector is devoid of RV E1 protein-encoding nucleotide sequence.
17. A virus packaging cell which generates the chimeric viral particle of claim 10 , wherein the virus packaging cell's genome comprises:
a) a nucleotide sequence encoding RV structural proteins C, E2 and E1; and
b) an expression vector comprising:
i) a promoter;
ii) a first nucleotide sequence, linked in translation frame to the promoter, encoding RV proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of E1 protein; and
iii) a second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encoding an immunogenic foreign viral protein;
wherein the expression vector is devoid of RV E1 protein-encoding nucleotide sequence.
18. An isolated expression vector comprising:
i) a promoter;
ii) a first nucleotide sequence, linked in translation frame to the promoter, encoding RV proteins, wherein the proteins encoded by the first nucleotide sequence are devoid of E1 protein; and
iii) a second nucleotide sequence, linked in translation frame to the first nucleotide sequence, encoding an immunogenic foreign viral protein;
wherein the expression vector is devoid of RV E1 protein-encoding nucleotide sequence.
19. The isolated expression vector of claim 18 , wherein immunogenic foreign viral protein is selected from the group consisting of RSV F protein and HN protein of hPIV-3.
20. The isolated expression vector of claim 19 , further comprising a third nucleotide sequence, linked in translation frame to the first or the second nucleotide sequence, encoding HN of hPIV-3.