Compositions and uses therefor
The invention is directed to the use of (i) a first antigen corresponding to a target antigen of interest, together with (ii) a second antigen, corresponding to a modified form of the target antigen, whose rate of intracellular proteolytic degradation is increased, enhanced or otherwise elevated relative to the first antigen, in compositions and methods for inducing both humoral and cellular immunity in an individual. The ability to provide compositions, which are capable of inducing both host-protective antibody and cell-mediated immune responses, facilitates the generation of immunogenic compositions capable of combating, inter alia, conditions that have long latency periods and, therefore, benefit from the dual approach of prophylaxis and therapy in one delivery.
1. A method of eliciting a humoral and a cellular immune response against a target antigen, comprising contacting at least one recipient cell with a composition comprising a first antigen corresponding to the target antigen, and a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, whereby said first antigen and said second antigen are expressed together in the same recipient cell or expressed separately in different recipient cells.
2. The method of claim 1 , wherein the recipient cell(s) is selected from a dendritic cell, a macrophage or a B cell.
3. A method of eliciting a humoral and a cellular immune response against a target antigen, comprising contacting at least one recipient cell with at least one nucleic acid composition comprising a first polynucleotide encoding a first antigen corresponding to the target antigen, and a second polynucleotide encoding a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, wherein said first polynucleotide and said second polynucleotide are expressed from different constructs, whereby said first antigen and said second antigen are expressed together in the same recipient cell or expressed separately in different recipient cells.
4. The method of claim 3 , wherein the nucleic acid composition is produced by optimising the codon composition of a parent polynucleotide encoding an antigen selected from the group consisting of the first antigen and the second antigen to construct a codon optimised polynucleotide whereby expression of the antigen from the codon optimised polynucleotide in said at least one recipient cell is increased, enhanced or otherwise elevated relative to that from said parent polynucleotide.
5. The method of claim 3 , wherein said codon composition is optimised by: selecting a first codon of the parent polynucleotide for replacement with a synonymous codon, wherein the first codon is selected on the basis that it has a higher translational efficiency than said synonymous codon in said at least one recipient cell, and replacing said first codon with said synonymous codon to construct said codon optimised polynucleotide.
6. The method of claim 3 , wherein said codon composition is optimised so that the antigen is expressible at a higher level in said recipient cell than in another cell.
7. The method of claim 3 , wherein said codon composition is optimised by: selecting a first codon of the parent polynucleotide for replacement with a synonymous codon which has a higher translational efficiency in said recipient cell than in another cell; and replacing said first codon with said synonymous codon to form said codon optimised polynucleotide.
8. The method of claim 3 , wherein the recipient cell(s) is selected from a dendritic cell, a macrophage or a B cell.
9. A method for modulating an immune response, comprising administering to a patient in need of such treatment a composition comprising (a) a first antigen corresponding to a target antigen, together with a second antigen corresponding to the target antigen and comprising an intracellular degradation signal that is absent from the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen; (b) a first polynucleotide encoding a first antigen corresponding to a target antigen, a second polynucleotide encoding a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, wherein said first polynucleotide and said second polynucleotide are expressed from different constructs; or (c) antigen-presenting cells which have been contacted with a first antigen corresponding to a target antigen or with a polynucleotide from which the first antigen is expressible, and with a second antigen corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the first and second antigens are physically separated from each other, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen wherein the intracellular degradation signal is a ubiquitin or with a polynucleotide from which the second antigen is expressible, for a time and under conditions sufficient to express a processed form of said first antigen, and a processed form of said second antigen, for presentation to, and modulation of, T cells.
10. A method for treatment and/or prophylaxis of a disease or condition, comprising administering to a patient in need of such treatment an effective amount of a composition comprising (a) a first antigen corresponding to a target antigen, together with a second antigen corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other; (b) a first polynucleotide encoding a first antigen corresponding to a target antigen, a second polynucleotide encoding a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, wherein said first polynucleotide and said second polynucleotide are expressed from different constructs; or (c) antigen-presenting cells which have been contacted with a first antigen corresponding to a target antigen or with a polynucleotide from which the first antigen is expressible, and with a second antigen corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, or with a polynucleotide from which the second antigen is expressible, for a time and under conditions sufficient to express a processed form of said first antigen, and a processed form of said second antigen, for presentation to, and modulation of, T cells.
11. A method for eliciting a humoral and a cellular immune response against a target antigen, comprising co-administering to a patient:
a first antigen corresponding to the target antigen, or a polynucleotide from which the first antigen is expressible; and
a second antigen corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, or a polynucleotide from which the second antigen is expressible.
12. A method for eliciting a humoral and a cellular immune response against a target antigen, comprising co-administering to a patient: a polynucleotide from which a first antigen, corresponding to the target antigen, is expressible; and a polynucleotide from which a second antigen, corresponding to the target antigen, is expressible, wherein the second antigen comprises an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen.
13. A method for eliciting a humoral and a cellular immune response against a target antigen, comprising co-administering to a patient:
a first antigen corresponding to the target antigen; and
a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent from the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen.
14. A method for eliciting a humoral and a cellular immune response against a target antigen, comprising co-administering to a patient:
antigen-presenting cells which have been contacted with a first antigen corresponding to the target antigen, or with a polynucleotide from which the first antigen is expressible, for a time and under conditions sufficient to express a processed form of said first antigen for presentation to, and modulation of, T cells; and
antigen-presenting cells which have been contacted with a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, or with a polynucleotide from which the second antigen is expressible, for a time and under conditions sufficient to express a processed form of said second antigen for presentation to, and modulation of, T cells,
wherein the antigen-presenting cells which have been contacted with the first antigen and the antigen-presenting cells which have been contacted with the second antigen may be the same or different.
15. A method for modulating an immune response, comprising administering to a patient in need of such treatment at least one composition comprising a first polynucleotide encoding a first antigen corresponding to a target antigen, a second polynucleotide encoding a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, wherein said first polynucleotide and said second polynucleotide are expressed from different regulatory constructs.
16. A method for modulating an immune response, comprising administering to a patient in need of such treatment the composition comprising antigen-presenting cells which have been contacted with a first antigen corresponding to the target antigen or with a polynucleotide from which the first antigen is expressible, and with a second antigen corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, or with a polynucleotide from which the second antigen is expressible, for a time and under conditions sufficient to express a processed form of said first antigen, and a processed form of said second antigen, for presentation to, and modulation of, T cells.
17. A method for treatment and/or prophylaxis of a disease or condition, comprising administering to a patient in need of such treatment an effective amount of at least one composition comprising a first polynucleotide encoding a first antigen corresponding to a target antigen, a second polynucleotide encoding a second antigen, corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, wherein said first polynucleotide and said second polynucleotide are expressed from different constructs.
18. A method for treatment and/or prophylaxis of a disease or condition, comprising administering to a patient in need of such treatment an effective amount of the composition comprising antigen-presenting cells which have been contacted with a first antigen corresponding to the target antigen or with a polynucleotide from which the first antigen is expressible, and with a second antigen corresponding to the target antigen and comprising an intracellular degradation signal that is absent in the first antigen, wherein the presence of the intracellular degradation signal increases the rate of intracellular proteolytic degradation of the second antigen relative to the first antigen, wherein the intracellular degradation signal is a ubiquitin, wherein the first and second antigens are physically separated from each other, wherein the first antigen elicits a humoral immune response to the target antigen and wherein the second antigen elicits a cellular immune response to the target antigen, or with a polynucleotide from which the second antigen is expressible, for a time and under conditions sufficient to express a processed form of said first antigen, and a processed form of said second antigen, for presentation to, and modulation of, T cells.