Recombinant vector

Abstract

The present invention relates to recombinant vectors, particularly recombinant vectors comprising a molecular adjuvant. The invention extends to pharmaceutical compositions and vaccines comprising the recombinant vector, to their use in therapy, and processes for making such pharmaceutical compositions. The invention also encompasses novel cell lines for producing the recombinant vectors.

Description

[0001]RECOMBINANT VECTOR The present invention relates to recombinant vectors, and particularly, although not exclusively, to recombinant vectors comprising a molecular adjuvant. The invention extends to pharmaceutical compositions and vaccines comprising the recombinant vector, to their use in therapy, for example for treating, preventing, or ameliorating an infectious disease or cancer, and processes for making such pharmaceutical compositions. The invention also encompasses novel cell lines for producing the recombinant vectors. Immunisation is the most effective public health tool to control infectious disease. Moreover, it is extremely cost-effective, given that treatment of disease is far more expensive than disease prevention. Although more than 70 vaccines have been created, only two diseases have been eradicated, namely rinderpest in cattle and smallpox in man. Terrible diseases with an enormous burden on global health such as malaria, tuberculosis, and AIDS remain uncontrolled. When vaccines alone are poorly immunogenic, immunogenicity is improved in a formulation that includes an adjuvant. Despite extensive evaluation of a large number of candidates over many years, only few adjuvants are currently approved, and some have debatable safety records. In addition, adjuvants or immune activating compounds are also used in therapeutic settings, where the promotion of immune activation is needed to disrupt immunosuppression. This is typically illustrated in the cancer field, where immunotherapy is used to counter immune suppression in the tumour environment. This can be achieved with immunocytokines and antigen-specific vaccines, many of which are limited in their immunogenic capacity. An approach that has not been explored to enhance immune activation during immunisation is the maximisation of the ability of the host cell machinery to sense a vaccine agent via its genome. Cells have evolved multiple strategies to defend from pathogen invasion, and the recognition of DNA has emerged as critical for immune activation in defensive processes, as well as inflammation, cancer, and autoimmune diseases. Although it has been known for decades that DNA activates immune responses, only recently have we started to identify the molecules in our cells that are responsible for these responses and how they work. How to therapeutically manipulate DNA sensing pathways in vaccinology, however, remains largely unexplored, in part because this goal requires a comprehensive understanding of how DNA recognition activates innate immune signalling, as well as how to engineer vaccine tools that harness DNA sensing immune potential. Cytosolic-replicating DNA viruses are a unique class of viruses capable of producing large quantities of DNA genomes in the cell cytosol. However, the immunogenic potential of this feature (e.g., cytosolic DNA accumulation) remains unexploited. Modified vaccinia Ankara (MVA) is an extremely attenuated non-replicating strain of the cytosolic-replicating DNA virus, vaccinia virus (VACV) (1,2), that is currently used as the vaccine against other pathogenic members of the orthopoxvirus (OPXV) genus, monkeypox virus (MPXV) or variola virus (VARV), due to antigenic cross-reactivity (3–5). MVA is also used as a heterologous vaccine vector carrying antigens for other pathogens, such as ebolavirus (EBOV). MVA is capable of inducing protective immunity against these diseases, but there are concerns about how immunogenic MVA actually is; one dose of the current MVA vaccine yields 78% efficacy against MPXV infection (6). This is best illustrated by the fact that despite a wide range of pre-clinical and clinical trials, MVA has only been approved as part of one vaccine regimen against a non-poxviral pathogen, where it acts as the boost to a prime by an adenoviral vector against ebolavirus (7). Thus, MVA appears to be limited in its immunogenicity compared to other viral vaccine vectors which are being developed. There are particular concerns about the generation of neutralising antibodies (nAbs) (8), which are an important correlate of protection for many infections which may limit the number of pathogens which MVA is a suitable vaccine vector against. It could be hypothesised that the retention of several immunomodulatory genes places a ceiling on the immunogenic capacity of MVA as it encodes functional copies of C6L (9), E5R (10), F17R (11), and N1L (30). There is, therefore, a need for a strategy that effectively improves the immune responses induced upon vaccination, and the immunogenicity of current and future vaccines, which utilises DNA sensing pathways, such as the cyclic GMP–AMP synthase (cGAS)-STING signalling axis. The cGAS-STING signalling axis can be activated by cytosolic DNA, including both non- self DNA and self DNA. This axis is used by the innate immune system to monitor invading pathogens and / or damage. Double-stranded DNA (dsDNA)-induced activation of cGAS can occur, for example, through pathogen infection or cellular stress. Upon binding dsDNA, cGAS dimers assemble on the dsDNA, leading to enzymatic activation of cGAS and synthesis of the second messenger, 2′3′ cyclic GMP–AMP (cGAMP). cGAMP then binds to stimulator of interferon genes (STING) dimers localised at the endoplasmic reticulum (ER) membrane, leading to conformational changes that trigger STING oligomerisation, liberation from anchoring factors, interaction with trafficking factors, and, finally, incorporation into coatomer protein complex II (COPII) vesicles. On passing through the ER–Golgi intermediate compartment (ERGIC) and Golgi, STING oligomers recruit TANK-binding kinase 1 (TBK1), which autophosphorylates, phosphorylates STING at Ser366, and phosphorylates interferon regulatory factor 3 (IRF3) when this recognises phosphorylated STING oligomers. STING oligomerisation is therefore a critical scaffold for innate immune activation. The phosphorylation of IRF3 by TBK1 enables IRF3 dimerisation and translocation to the nucleus, to thereby induce gene expression of type I interferons, interferon-stimulated genes (ISGs), and several other inflammatory mediators, pro-apoptotic genes, and chemokines. Activation of STING also leads to NF- κB activation and the formation of LC3+ vesicles (autophagosomes) by a non-canonical mechanism of autophagy. Besides activating STING in the infected or stressed cell, cGAMP also has the capacity to boost innate immune responses in surrounding non-infected cells. cGAMP diffuses through cell-to-cell junctions (31), and is exported to, and subsequently imported from, the extracellular milieu (32). cGAMP activates STING in these bystander cells spreading and boosting innate activation. The inventors have discovered a novel strategy to enhance innate immune activation, by arming a cytosolic-replicating DNA viral vector with a cyclic di-nucleotide synthetase enzyme gene. The inventors have discovered that this strategy delivers the pattern recognition receptor (PRR), e.g., cGAS, and the dsDNA to the same cell, resulting in immediate activation of the sensor, production of 2’3’-cGAMP, and induction of signalling downstream of STING. As a consequence, the viral vector according to the invention, results in higher production of interferons and immune cytokines, and enhanced immunogenicity. Thus, according to a first aspect of the invention, there is provided a recombinant vector comprising a cytosolic-replicating DNA virus encoding at least one cyclic di-nucleotide synthetase enzyme. Cyclic di-nucleotide synthetases (e.g., cGAS) are antiviral molecules, driving expression of interferons and interferon-stimulated genes (ISGs). Arming a virus with an antiviral molecule is therefore contradictory, and would be expected to result in selective pressure where the selected virus has gained mutations that inactivate the antiviral molecule, making the armed vector not possible. However, the inventors have surprisingly circumvented this limitation by successfully producing a recombinant vector armed with a cyclic di-nucleotide synthetase gene. In order to produce the recombinant vector of the invention, the inventors have also generated a producer cell line, in which the cyclic di- nucleotide synthetase gene is left intact and without affect, thus enabling the production of the armed recombinant vector, that is, the producer cell line is modified such that the cyclic di-nucleotide synthetase gene has no detrimental effect on the cell. To achieve this, the inventors have knocked out STING in the producer cell line, thus negating the possibility of cGAS to signal. As such, there is no detrimental effect of cGAS signalling on the virus. Instead, the virus, and hence vaccine vector, is stable, and there is no pressure for the virus to eventually mutate and inactivate cGAS. As such, the recombinant vector comprising the synthetase gene (e.g., cGAS) is able to drive enhanced innate immune activation when used therapeutically, as described herein. It will be appreciated by the skilled person that a cytosolic-replicating DNA virus is one which is capable of producing large quantities of DNA genomes in the cell cytosol. In one embodiment, the cytosolic-replicating DNA virus may be selected from the group of viruses consisting of: a poxvirus, an asfarvirus, and an iridovirus. The asfarvirus may be African swine fever virus (ASFV). The poxvirus may be selected from a group of poxviruses consisting of: Avipoxvirus, Capripoxvirus, Centapoxvirus, Cervidpoxvirus, Crocodylidpoxvirus, Leporipoxvirus, Macropopoxvirus, Molluscipoxvirus, Mustelpoxvirus, Orthopoxvirus, Oryzopoxvirus, Parapoxvirus, Pteropopoxvirus, Salmonpoxvirus, Sciuripoxvirus, Suipoxvirus, Vespertilionpoxvirus, Yatapoxvirus, Alphaentomopoxvirus, Betaentomopoxvirus, Deltaentomopoxvirus, Diachasmimorpha entomopoxvirus, and Gammaentomopoxvirus. In one embodiment, the poxvirus is Parapoxvirus. Typically, the poxvirus is an Orthopoxvirus. In one embodiment, the virus is an Avipoxvirus. The Avipoxvirus may be selected from a group of Avipoxviruses consisting of: fowlpox virus, pigeonpox virus, and canarypox virus. In one embodiment, the virus is an Orthopoxvirus. The Orthopoxvirus may be selected from a group of Orthopoxviruses consisting of: Camelpox virus, Cowpox virus, Ectromelia virus, Horsepox virus, Monkeypox virus, Raccoonpox virus, Skunkpox virus, Taterapox virus, Uasin Gishu virus, Vaccinia virus, Variola virus, and Volepox virus. Typically, the Orthopoxvirus is Vaccinia virus. In one embodiment, the virus is a Vaccinia virus. In another embodiment, the virus is derived from a Vaccinia virus strain. The Vaccinia virus strain may be selected from a group of Vaccinia virus strains consisting of: NYVAC, Western Reserve (WR), Lister (and derivatives LC16m0 and LC16m8), Wyeth, Bern, Ankara, Tian-Tian, Ikeda, and Modified vaccinia Ankara (MVA). Typically, however, the Vaccinia virus strain is a Modified vaccinia Ankara (MVA). In one embodiment, the virus may be replicative or non-replicative. Typically, however, the virus is non-replicative. In one embodiment, the recombinant vector may comprise a cytosolic-replicating DNA viral genome. Accordingly, it will be appreciated that the cytosolic-replicating DNA viral genome may be derived from any of the cytosolic-replicating DNA viruses as described above. It will be appreciated that cyclic di-nucleotide synthetase enzymes are mammalian pattern recognition receptors (PRRs), which detect double stranded DNA (dsDNA) in the cytoplasm and induce antiviral signalling via production of the secondary messenger 2’3’-cyclic GMP-AMP (2’3’-cGAMP). In one embodiment, the at least one cyclic di-nucleotide synthetase enzyme may be derived from an animal, bacteria, fungus, or virus. The cyclic di-nucleotide synthetase enzyme may not be derived from a bacterium. Typically, however, the cyclic di- nucleotide synthetase enzyme is derived from an animal. More typically, the cyclic di- nucleotide synthetase enzyme is derived from a vertebrate. More typically, the cyclic di- nucleotide synthetase enzyme is derived from a mammal. Yet more typically, the cyclic di-nucleotide synthetase enzyme is derived from a human. It will be appreciated that the product of mammalian cGAS (i.e., 2’3’-cGAMP) is more potent than those of bacterial cyclases (e.g., c-di-GMP and c-di-AMP) because the affinity of mammalian STING to 2’3’-cGAMP is higher. It will be appreciated that if the recombinant vector of the invention is to be used as human therapeutic, the cyclic di-nucleotide synthetase enzyme is derived from a human. It will also be appreciated that if the recombinant vector of the invention is to be used as a non-human therapeutic, the cyclic di-nucleotide synthetase enzyme is derived from the same species for which the therapeutic is intended for use in treating. In one embodiment, the at least one cyclic di-nucleotide synthetase enzyme may be selected from the group of cyclic di-nucleotide synthetase enzymes consisting of: cyclic GTP-ATP synthase (cGAS), deadenylate cyclase (DAC), DncV, Hypr-GGDEF, DisA, and diguanylate cyclase (DGC). In one embodiment, the at least one cyclic di-nucleotide synthetase enzyme is cyclic GTP-ATP synthase (cGAS). Typically, the at least one cyclic di-nucleotide synthetase enzyme is human cyclic GTP-ATP synthase (cGAS). The inventors have generated embodiments of the vector of the invention comprising a copy of the cGAS gene; this vector may be referred to herein as “self-adjuvanting” Modified vaccinia Ankara (saMVA) wild-type (WT), and the WT cGAS enzyme may be referred to herein as cGAS. In one embodiment, cGAS may comprise the amino acid sequence represented herein as SEQ ID No: 1, as follows: MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPS DATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKG VVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRK IIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWR LSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTY FLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF [SEQ ID No: 1] In one embodiment, cGAS may be encoded by the nucleotide sequence represented herein as SEQ ID No: 2, as follows: ATGCAGCCTTGGCACGGAAAGGCCATGCAGAGAGCTTCCGAGGCCGGAGCCACTGCCCCCAAGGCTTCCGCACGGAATGCCAGGGGCGCCCCGA TGGATCCCACCGAGTCTCCGGCTGCCCCCGAGGCCGCCCTGCCTAAGGCGGGAAAGTTCGGCCCCGCCAGGAAGTCGGGATCCCGGCAGAAAAA GAGCGCCCCGGACACCCAGGAGAGGCCGCCCGTCCGCGCAACTGGGGCCCGCGCCAAAAAGGCCCCTCAGCGCGCCCAGGACACGCAGCCGTCT GACGCCACCAGCGCCCCTGGGGCAGAGGGGCTGGAGCCTCCTGCGGCTCGGGAGCCGGCTCTTTCCAGGGCTGGTTCTTGCCGCCAGAGGGGCG CGCGCTGCTCCACGAAGCCAAGACCTCCGCCCGGGCCCTGGGACGTGCCCAGCCCCGGCCTGCCGGTCTCGGCCCCCATTCTCGTACGGAGGGA TGCGGCGCCTGGGGCCTCGAAGCTCCGGGCGGTTTTGGAGAAGTTGAAGCTCAGCCGCGATGATATCTCCACGGCGGCGGGGATGGTGAAAGGG GTTGTGGACCACCTGCTGCTCAGACTGAAGTGCGACTCCGCGTTCAGAGGCGTCGGGCTGCTGAACACCGGGAGCTACTATGAGCACGTGAAGA TTTCTGCACCTAATGAATTTGATGTCATGTTTAAACTGGAAGTCCCCAGAATTCAACTAGAAGAATATTCCAACACTCGTGCATATTACTTTGT GAAATTTAAAAGAAATCCGAAAGAAAATCCTCTGAGTCAGTTTTTAGAAGGTGAAATATTATCAGCTTCTAAGATGCTGTCAAAGTTTAGGAAA ATCATTAAGGAAGAAATTAACGACATTAAAGATACAGATGTCATCATGAAGAGGAAAAGAGGAGGGAGCCCTGCTGTAACACTTCTTATTAGTG AAAAAATATCTGTGGATATAACCCTGGCTTTGGAATCAAAAAGTAGCTGGCCTGCTAGCACCCAAGAAGGCCTGCGCATTCAAAACTGGCTTTC AGCAAAAGTTAGGAAGCAACTACGACTAAAGCCATTTTACCTTGTACCCAAGCATGCAAAGGAAGGAAATGGTTTCCAAGAAGAAACATGGCGG CTATCCTTCTCTCACATCGAAAAGGAAATTTTGAACAATCATGGAAAATCTAAAACGTGCTGTGAAAACAAAGAAGAGAAATGTTGCAGGAAAG ATTGTTTAAAACTAATGAAATACCTTTTAGAACAGCTGAAAGAAAGGTTTAAAGACAAAAAACATCTGGATAAATTCTCTTCTTATCATGTGAA AACTGCCTTCTTTCACGTATGTACCCAGAACCCTCAAGACAGTCAGTGGGACCGCAAAGACCTGGGCCTCTGCTTTGATAACTGCGTGACATAC TTTCTTCAGTGCCTCAGGACAGAAAAACTTGAGAATTATTTTATTCCTGAATTCAATCTATTCTCTAGCAACTTAATTGACAAAAGAAGTAAGG AATTTCTGACAAAGCAAATTGAATATGAAAGAAACAATGAGTTTCCAGTTTTTGATGAATTT [SEQ ID No: 2] It will be appreciated that the nucleotide sequence of SEQ ID No: 2 represents the wild- type nucleotide sequence encoding cGAS. In another embodiment, cGAS may be encoded by the nucleotide sequence represented herein as SEQ ID No: 5, as follows: ATGCAACCATGGCATGGAAAGGCTATGCAAAGAGCTTCTGAAGCGGGAGCTACAGCTCCAAAAGCTTCTGCTAGAAATGCTAGAGGTGCTCCAA TGGACCCAACAGAATCTCCAGCTGCTCCAGAAGCTGCTTTACCAAAAGCGGGAAAATTTGGACCGGCGAGAAAGTCTGGATCGAGACAAAAAAA GTCTGCGCCGGACACACAAGAAAGACCACCAGTTAGAGCTACAGGTGCCAGAGCTAAAAAAGCTCCACAAAGAGCGCAAGATACCCAACCATCT GATGCTACATCTGCTCCAGGTGCTGAAGGATTAGAACCACCAGCTGCTAGAGAACCAGCTCTATCAAGAGCTGGATCTTGCAGACAAAGAGGTG CTAGATGTTCCACAAAACCTAGACCACCACCAGGACCATGGGATGTACCAAGTCCAGGATTACCAGTATCTGCGCCGATCCTAGTTAGAAGAGA TGCTGCTCCTGGTGCCTCTAAACTAAGAGCGGTACTAGAGAAGCTAAAGCTATCCAGAGATGACATCTCCACAGCTGCCGGAATGGTTAAGGGT GTAGTAGACCACCTACTACTAAGATTGAAGTGCGACTCTGCGTTCAGAGGTGTCGGACTATTGAACACCGGATCTTACTACGAGCACGTCAAAA TCTCTGCCCCGAACGAATTCGACGTCATGTTCAAACTAGAGGTCCCGAGAATCCAGCTAGAGGAATACTCTAACACCAGAGCGTACTACTTCGT CAAGTTCAAGAGAAACCCGAAAGAGAACCCGCTATCGCAATTTTTGGAGGGAGAAATCCTATCCGCGTCCAAGATGCTATCCAAGTTCAGAAAG ATCATCAAAGAAGAGATCAACGACATCAAGGACACCGACGTCATCATGAAGAGAAAGAGAGGTGGAAGTCCGGCGGTCACACTACTAATCTCTG AAAAGATCTCCGTCGACATCACCCTAGCGTTGGAGTCTAAATCTTCTTGGCCAGCGTCTACCCAAGAGGGACTAAGAATCCAAAATTGGCTATC CGCGAAAGTCAGAAAGCAGTTGAGATTGAAGCCGTTCTACTTGGTCCCGAAGCACGCTAAAGAAGGAAACGGATTCCAAGAAGAGACTTGGAGA [SEQ ID No: 5] It will be appreciated that the nucleotide sequence of SEQ ID No: 5 represents a nucleotide sequence encoding cGAS which has been codon-optimised for Vaccinia virus. In one embodiment, therefore, the at least one cyclic di-nucleotide synthetase enzyme may comprise an amino acid sequence substantially as set out in SEQ ID No: 1, or a fragment or variant thereof. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may be encoded by a nucleic acid sequence substantially as set out in SEQ ID Nos: 2 or 5, or a fragment or variant thereof. The inventors have generated embodiments of the vector of the invention comprising a catalytically inactive copy of the cGAS gene; this vector may be referred to herein as saMVA CI, and the inactive copy of the cGAS enzyme may be referred to herein as cGAS- CI or cGAS E225A / D227A. In one embodiment, cGAS-CI may comprise the amino acid sequence represented herein as SEQ ID No: 3, as follows: MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPS DATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKG VVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNAFAVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRK IIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWR LSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTY FLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF [SEQ ID No: 3] In one embodiment, cGAS-CI may be encoded by the nucleotide sequence represented herein as SEQ ID No: 4, as follows: ATGCAGCCTTGGCACGGAAAGGCCATGCAGAGAGCTTCCGAGGCCGGAGCCACTGCCCCCAAGGCTTCCGCACGGAATGCCAGGGGCGCCCCGA TGGATCCCACCGAGTCTCCGGCTGCCCCCGAGGCCGCCCTGCCTAAGGCGGGAAAGTTCGGCCCCGCCAGGAAGTCGGGATCCCGGCAGAAAAA GAGCGCCCCGGACACCCAGGAGAGGCCGCCCGTCCGCGCAACTGGGGCCCGCGCCAAAAAGGCCCCTCAGCGCGCCCAGGACACGCAGCCGTCT GACGCCACCAGCGCCCCTGGGGCAGAGGGGCTGGAGCCTCCTGCGGCTCGGGAGCCGGCTCTTTCCAGGGCTGGTTCTTGCCGCCAGAGGGGCG CGCGCTGCTCCACGAAGCCAAGACCTCCGCCCGGGCCCTGGGACGTGCCCAGCCCCGGCCTGCCGGTCTCGGCCCCCATTCTCGTACGGAGGGA TGCGGCGCCTGGGGCCTCGAAGCTCCGGGCGGTTTTGGAGAAGTTGAAGCTCAGCCGCGATGATATCTCCACGGCGGCGGGGATGGTGAAAGGG GTTGTGGACCACCTGCTGCTCAGACTGAAGTGCGACTCCGCGTTCAGAGGCGTCGGGCTGCTGAACACCGGGAGCTACTATGAGCACGTGAAGA TTTCTGCACCTAATGcATTTGcTGTCATGTTTAAACTGGAAGTCCCCAGAATTCAACTAGAAGAATATTCCAACACTCGTGCATATTACTTTGT GAAATTTAAAAGAAATCCGAAAGAAAATCCTCTGAGTCAGTTTTTAGAAGGTGAAATATTATCAGCTTCTAAGATGCTGTCAAAGTTTAGGAAA ATCATTAAGGAAGAAATTAACGACATTAAAGATACAGATGTCATCATGAAGAGGAAAAGAGGAGGGAGCCCTGCTGTAACACTTCTTATTAGTG AAAAAATATCTGTGGATATAACCCTGGCTTTGGAATCAAAAAGTAGCTGGCCTGCTAGCACCCAAGAAGGCCTGCGCATTCAAAACTGGCTTTC AGCAAAAGTTAGGAAGCAACTACGACTAAAGCCATTTTACCTTGTACCCAAGCATGCAAAGGAAGGAAATGGTTTCCAAGAAGAAACATGGCGG CTATCCTTCTCTCACATCGAAAAGGAAATTTTGAACAATCATGGAAAATCTAAAACGTGCTGTGAAAACAAAGAAGAGAAATGTTGCAGGAAAG ATTGTTTAAAACTAATGAAATACCTTTTAGAACAGCTGAAAGAAAGGTTTAAAGACAAAAAACATCTGGATAAATTCTCTTCTTATCATGTGAA AACTGCCTTCTTTCACGTATGTACCCAGAACCCTCAAGACAGTCAGTGGGACCGCAAAGACCTGGGCCTCTGCTTTGATAACTGCGTGACATAC TTTCTTCAGTGCCTCAGGACAGAAAAACTTGAGAATTATTTTATTCCTGAATTCAATCTATTCTCTAGCAACTTAATTGACAAAAGAAGTAAGG AATTTCTGACAAAGCAAATTGAATATGAAAGAAACAATGAGTTTCCAGTTTTTGATGAATTT [SEQ ID No: 4] It will be appreciated that the nucleotide sequence of SEQ ID No: 4 represents the wild- type nucleotide sequence encoding cGAS-CI. In another embodiment, cGAS-CI may be encoded by the nucleotide sequence represented herein as SEQ ID No: 6, as follows: ATGCAACCATGGCATGGAAAGGCTATGCAAAGAGCTTCTGAAGCGGGAGCTACAGCTCCAAAAGCTTCTGCTAGAAATGCTAGAGGTGCTCCAA TGGACCCAACAGAATCTCCAGCTGCTCCAGAAGCTGCTTTACCAAAAGCGGGAAAATTTGGACCGGCGAGAAAGTCTGGATCGAGACAAAAAAA GTCTGCGCCGGACACACAAGAAAGACCACCAGTTAGAGCTACAGGTGCCAGAGCTAAAAAAGCTCCACAAAGAGCGCAAGATACCCAACCATCT GATGCTACATCTGCTCCAGGTGCTGAAGGATTAGAACCACCAGCTGCTAGAGAACCAGCTCTATCAAGAGCTGGATCTTGCAGACAAAGAGGTG CTAGATGTTCCACAAAACCTAGACCACCACCAGGACCATGGGATGTACCAAGTCCAGGATTACCAGTATCTGCGCCGATCCTAGTTAGAAGAGA TGCTGCTCCTGGTGCCTCTAAACTAAGAGCGGTACTAGAGAAGCTAAAGCTATCCAGAGATGACATCTCCACAGCTGCCGGAATGGTTAAGGGT GTAGTAGACCACCTACTACTAAGATTGAAGTGCGACTCTGCGTTCAGAGGTGTCGGACTATTGAACACCGGATCTTACTACGAGCACGTCAAAA TCTCTGCCCCGAACGcATTCGcCGTCATGTTCAAACTAGAGGTCCCGAGAATCCAGCTAGAGGAATACTCTAACACCAGAGCGTACTACTTCGT CAAGTTCAAGAGAAACCCGAAAGAGAACCCGCTATCGCAATTTTTGGAGGGAGAAATCCTATCCGCGTCCAAGATGCTATCCAAGTTCAGAAAG ATCATCAAAGAAGAGATCAACGACATCAAGGACACCGACGTCATCATGAAGAGAAAGAGAGGTGGAAGTCCGGCGGTCACACTACTAATCTCTG AAAAGATCTCCGTCGACATCACCCTAGCGTTGGAGTCTAAATCTTCTTGGCCAGCGTCTACCCAAGAGGGACTAAGAATCCAAAATTGGCTATC CGCGAAAGTCAGAAAGCAGTTGAGATTGAAGCCGTTCTACTTGGTCCCGAAGCACGCTAAAGAAGGAAACGGATTCCAAGAAGAGACTTGGAGA CTATCGTTCTCCCACATCGAGAAAGAAATCTTGAACAACCACGGAAAGTCCAAGACCTGCTGCGAGAACAAAGAGGAAAAGTGCTGTAGAAAGG ACTGCCTAAAGCTAATGAAGTACCTACTAGAGCAGTTGAAAGAGAGATTCAAGGACAAGAAGCACCTAGACAAGTTCTCGTCCTACCACGTAAA GACCGCCTTTTTCCATGTCTGTACACAGAACCCGCAAGACTCTCAGTGGGACAGAAAAGATTTGGGACTATGCTTCGACAACTGCGTGACCTAC TTCCTACAGTGTCTAAGAACCGAGAAGTTGGAGAACTACTTCATCCCCGAGTTCAACCTATTCTCCTCCAACCTAATCGACAAGAGATCCAAAG AGTTCTTGACCAAGCAGATCGAGTACGAGAGAAACAACGAGTTCCCGGTGTTCGATGAATTT [SEQ ID No: 6] It will be appreciated that the nucleotide sequence of SEQ ID No: 6 represents a nucleotide sequence encoding cGAS-CI which has been codon-optimised for Vaccinia virus. In one embodiment, therefore, the at least one cyclic di-nucleotide synthetase enzyme may comprise an amino acid sequence substantially as set out in SEQ ID No: 3, or a fragment or variant thereof. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may be encoded by a nucleic acid sequence substantially as set out in SEQ ID Nos: 4 or 6, or a fragment or variant thereof. The inventors have also identified embodiments of the vector of the invention comprising a mutant copy of the cGAS gene; this vector may be referred to herein as saMVA-M, and inactive copies of the cGAS enzyme may be referred to herein as cGAS mutants, cGAS R255E, or cGAS NN153 / 154AA. These cGAS mutants cannot be degraded by a cell, and the inventors predict that they may, therefore, trigger stronger responses. In one embodiment, cGAS R255E may comprise the amino acid sequence represented herein as SEQ ID No: 28, as follows: MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPS DATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKG VVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKENPKENPLSQFLEGEILSASKMLSKFRK IIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWR LSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTY FLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF [SEQ ID No: 28] In one embodiment, cGAS R255E may be encoded by the nucleotide sequence represented herein as SEQ ID No: 29, as follows: ATGCAACCATGGCATGGAAAGGCTATGCAAAGAGCTTCTGAAGCGGGAGCTACAGCTCCAAAAGCTTCTGCTAGAAATGCTAGAGGTGCTCCAA TGGACCCAACAGAATCTCCAGCTGCTCCAGAAGCTGCTTTACCAAAAGCGGGAAAATTTGGACCGGCGAGAAAGTCTGGATCGAGACAAAAAAA GTCTGCGCCGGACACACAAGAAAGACCACCAGTTAGAGCTACAGGTGCCAGAGCTAAAAAAGCTCCACAAAGAGCGCAAGATACCCAACCATCT GATGCTACATCTGCTCCAGGTGCTGAAGGATTAGAACCACCAGCTGCTAGAGAACCAGCTCTATCAAGAGCTGGATCTTGCAGACAAAGAGGTG CTAGATGTTCCACAAAACCTAGACCACCACCAGGACCATGGGATGTACCAAGTCCAGGATTACCAGTATCTGCGCCGATCCTAGTTAGAAGAGA TGCTGCTCCTGGTGCCTCTAAACTAAGAGCGGTACTAGAGAAGCTAAAGCTATCCAGAGATGACATCTCCACAGCTGCCGGAATGGTTAAGGGT GTAGTAGACCACCTACTACTAAGATTGAAGTGCGACTCTGCGTTCAGAGGTGTCGGACTATTGAACACCGGATCTTACTACGAGCACGTCAAAA TCTCTGCCCCGAACGAATTCGACGTCATGTTCAAACTAGAGGTCCCGAGAATCCAGCTAGAGGAATACTCTAACACCAGAGCGTACTACTTCGT CAAGTTCAAGGAAAACCCGAAAGAGAACCCGCTATCGCAATTTTTGGAGGGAGAAATCCTATCCGCGTCCAAGATGCTATCCAAGTTCAGAAAG ATCATCAAAGAAGAGATCAACGACATCAAGGACACCGACGTCATCATGAAGAGAAAGAGAGGTGGAAGTCCGGCGGTCACACTACTAATCTCTG AAAAGATCTCCGTCGACATCACCCTAGCGTTGGAGTCTAAATCTTCTTGGCCAGCGTCTACCCAAGAGGGACTAAGAATCCAAAATTGGCTATC CGCGAAAGTCAGAAAGCAGTTGAGATTGAAGCCGTTCTACTTGGTCCCGAAGCACGCTAAAGAAGGAAACGGATTCCAAGAAGAGACTTGGAGA CTATCGTTCTCCCACATCGAGAAAGAAATCTTGAACAACCACGGAAAGTCCAAGACCTGCTGCGAGAACAAAGAGGAAAAGTGCTGTAGAAAGG ACTGCCTAAAGCTAATGAAGTACCTACTAGAGCAGTTGAAAGAGAGATTCAAGGACAAGAAGCACCTAGACAAGTTCTCGTCCTACCACGTAAA GACCGCCTTTTTCCATGTCTGTACACAGAACCCGCAAGACTCTCAGTGGGACAGAAAAGATTTGGGACTATGCTTCGACAACTGCGTGACCTAC TTCCTACAGTGTCTAAGAACCGAGAAGTTGGAGAACTACTTCATCCCCGAGTTCAACCTATTCTCCTCCAACCTAATCGACAAGAGATCCAAAG AGTTCTTGACCAAGCAGATCGAGTACGAGAGAAACAACGAGTTCCCGGTGTTCGATGAATTT [SEQ ID No: 29] It will be appreciated that the nucleotide sequence of SEQ ID No: 29 represents a nucleotide sequence encoding cGAS R255E which has been codon-optimised for Vaccinia virus. In one embodiment, therefore, the at least one cyclic di-nucleotide synthetase enzyme may comprise an amino acid sequence substantially as set out in SEQ ID No: 28, or a fragment or variant thereof. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may be encoded by a nucleic acid sequence substantially as set out in SEQ ID No: 29, or a fragment or variant thereof. In one embodiment, cGAS NN153 / 154AA may comprise the amino acid sequence represented herein as SEQ ID No: 30, as follows: MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPS DATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKG VVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRK IIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWR LSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTY FLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERAAEFPVFDEF [SEQ ID No: 30] In one embodiment, cGAS NN153 / 154AA may be encoded by the nucleotide sequence represented herein as SEQ ID No: 31, as follows: ATGCAACCATGGCATGGAAAGGCTATGCAAAGAGCTTCTGAAGCGGGAGCTACAGCTCCAAAAGCTTCTGCTAGAAATGCTAGAGGTGCTCCAA TGGACCCAACAGAATCTCCAGCTGCTCCAGAAGCTGCTTTACCAAAAGCGGGAAAATTTGGACCGGCGAGAAAGTCTGGATCGAGACAAAAAAA GTCTGCGCCGGACACACAAGAAAGACCACCAGTTAGAGCTACAGGTGCCAGAGCTAAAAAAGCTCCACAAAGAGCGCAAGATACCCAACCATCT GATGCTACATCTGCTCCAGGTGCTGAAGGATTAGAACCACCAGCTGCTAGAGAACCAGCTCTATCAAGAGCTGGATCTTGCAGACAAAGAGGTG CTAGATGTTCCACAAAACCTAGACCACCACCAGGACCATGGGATGTACCAAGTCCAGGATTACCAGTATCTGCGCCGATCCTAGTTAGAAGAGA TGCTGCTCCTGGTGCCTCTAAACTAAGAGCGGTACTAGAGAAGCTAAAGCTATCCAGAGATGACATCTCCACAGCTGCCGGAATGGTTAAGGGT GTAGTAGACCACCTACTACTAAGATTGAAGTGCGACTCTGCGTTCAGAGGTGTCGGACTATTGAACACCGGATCTTACTACGAGCACGTCAAAA TCTCTGCCCCGAACGAATTCGACGTCATGTTCAAACTAGAGGTCCCGAGAATCCAGCTAGAGGAATACTCTAACACCAGAGCGTACTACTTCGT CAAGTTCAAGAGAAACCCGAAAGAGAACCCGCTATCGCAATTTTTGGAGGGAGAAATCCTATCCGCGTCCAAGATGCTATCCAAGTTCAGAAAG ATCATCAAAGAAGAGATCAACGACATCAAGGACACCGACGTCATCATGAAGAGAAAGAGAGGTGGAAGTCCGGCGGTCACACTACTAATCTCTG AAAAGATCTCCGTCGACATCACCCTAGCGTTGGAGTCTAAATCTTCTTGGCCAGCGTCTACCCAAGAGGGACTAAGAATCCAAAATTGGCTATC CGCGAAAGTCAGAAAGCAGTTGAGATTGAAGCCGTTCTACTTGGTCCCGAAGCACGCTAAAGAAGGAAACGGATTCCAAGAAGAGACTTGGAGA CTATCGTTCTCCCACATCGAGAAAGAAATCTTGAACAACCACGGAAAGTCCAAGACCTGCTGCGAGAACAAAGAGGAAAAGTGCTGTAGAAAGG ACTGCCTAAAGCTAATGAAGTACCTACTAGAGCAGTTGAAAGAGAGATTCAAGGACAAGAAGCACCTAGACAAGTTCTCGTCCTACCACGTAAA GACCGCCTTTTTCCATGTCTGTACACAGAACCCGCAAGACTCTCAGTGGGACAGAAAAGATTTGGGACTATGCTTCGACAACTGCGTGACCTAC TTCCTACAGTGTCTAAGAACCGAGAAGTTGGAGAACTACTTCATCCCCGAGTTCAACCTATTCTCCTCCAACCTAATCGACAAGAGATCCAAAG AGTTCTTGACCAAGCAGATCGAGTACGAGAGAGCCGCCGAGTTCCCGGTGTTCGATGAATTT [SEQ ID No: 31] It will be appreciated that the nucleotide sequence of SEQ ID No: 31 represents a nucleotide sequence encoding cGAS NN153 / 154AA which has been codon-optimised for Vaccinia virus. In one embodiment, therefore, the at least one cyclic di-nucleotide synthetase enzyme may comprise an amino acid sequence substantially as set out in SEQ ID No: 30, or a fragment or variant thereof. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may be encoded by a nucleic acid sequence substantially as set out in SEQ ID No: 31, or a fragment or variant thereof. Thus, the recombinant vector may comprise at least one gene encoding a cyclic di-nucleotide synthetase enzyme. In one embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least two, three, or four cyclic di-nucleotide synthetase enzymes. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least five, six, or seven cyclic di-nucleotide synthetase enzymes. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least eight, nine, or ten cyclic di-nucleotide synthetase enzymes. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least 11, 12, or 13 cyclic di-nucleotide synthetase enzymes. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least 14, 15, or 16 cyclic di-nucleotide synthetase enzymes. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least 17, 18, or 19 cyclic di-nucleotide synthetase enzymes. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least 20, 21, or 22 cyclic di-nucleotide synthetase enzymes. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme may comprise at least 23, 24, or 25 cyclic di-nucleotide synthetase enzymes. Typically, the at least one cyclic di-nucleotide synthetase enzyme may comprise about three or four cyclic di-nucleotide synthetase enzymes. In one embodiment, therefore, the recombinant vector may encode between two and 25 cyclic di-nucleotide synthetase enzymes. In one embodiment, therefore, the recombinant vector may comprise between two and 25 genes encoding a cyclic di-nucleotide synthetase enzyme. The at least two or more cyclic di-nucleotide synthetase enzymes may comprise the same cyclic di-nucleotide synthetase enzyme or different cyclic di-nucleotide synthetase enzymes. The at least two or more genes encoding a cyclic di-nucleotide synthetase enzyme may encode the same cyclic di-nucleotide synthetase enzyme or different cyclic di-nucleotide synthetase enzymes. In one embodiment, the at least two or more genes encoding cyclic di-nucleotide synthetase enzymes may be in tandem. It will be appreciated that in tandem means the at least two or more genes encoding the cyclic di-nucleotide synthetase enzymes are consecutive, and / or are under the control of one promoter. In one embodiment, the recombinant vector may encode at least three or four cyclic di- nucleotide synthetase enzymes, or it may comprise at least three or four genes encoding cyclic di-nucleotide synthetase enzymes. Referring to Figure 1, the inventors have designed embodiments of a MVA-cGAS vector design. In vectors saMVA WT and saMVA CI, the transgene, i.e., cGAS and cGAS-CI (cGAS E225A / D227A), respectively, is under the control of a viral promoter and the tetracycline regulatory element. In one embodiment, the gene encoding the at least one cyclic di-nucleotide synthetase enzyme may be operatively linked to a transcriptional and / or translational regulatory sequence. The transcriptional and / or translational regulatory sequence may comprise a promoter, enhancer, silencer, operator, 5’ untranslated region (UTR), and / or 3’ UTR. Typically, the transcriptional and / or translational regulatory sequence comprises a viral promoter and / or the operator (e.g. a tetracycline regulatory element). More typically, the transcriptional and / or translational regulatory sequence comprises a viral promoter and the operator (e.g. a tetracycline regulatory element). Accordingly, in one embodiment, the recombinant vector further comprises a viral promoter. In one embodiment, the recombinant vector comprises two viral promoters. The viral promoter may be selected from a group of viral promoters consisting of: p7.5 promoter, pE / L, mH5, pF13L, and p4b. Typically, the viral promotor is a p7.5 promoter. In some embodiments, the vector comprises a p7.5 promoter and a pF13L promoter. In one embodiment, the p7.5 promoter may comprise the nucleotide sequence represented herein as SEQ ID No: 7, as follows: TCCAAACCCACCCGCTTTTTATAGTAAGTTTTTCACCCATAAATAATAAATACAATAATTAATTTCTCGTAAAAGTAGAAAATATATTCTAATT TATTGCACGGTAAGGAAGTAGA [SEQ ID No: 7] In one embodiment, the pF13L promoter may comprise the nucleotide sequence represented herein as SEQ ID No: 8, as follows: GTTTTTATGTTAACTAA [SEQ ID No: 8] In one embodiment, therefore, the promoter may comprise a nucleotide sequence substantially as set out in SEQ ID Nos: 7 or 8, or a fragment or variant thereof. In another embodiment, the recombinant vector further comprises an operator. In one embodiment, the recombinant vector comprises two copies of the operator. The operator may be selected from a group of operators consisting of: TetO, CuO, tamoxifen operators, light-switchable operators, and bacterial riboswitches. The operator may also comprise any transcriptional element that provides inducible transcriptional control. Typically, the operator is TetO. In some embodiments, the recombinant vector comprises two copies of TetO. In one embodiment, the vector may comprise a nucleotide sequence encoding at least one cyclic di-nucleotide synthetase enzyme and / or a transcriptional and / or translational regulatory sequence inserted into a viral genome. In another embodiment, the vector may comprise a nucleotide sequence encoding at least one cyclic di-nucleotide synthetase enzyme and / or a transcriptional and / or translational regulatory sequence inserted into a viral genome at a specified locus. Accordingly, in one embodiment, the vector further comprises a locus comprising flanking genomic regions and / or genomic regions that allow recombination of foreign genetic material, e.g., a nucleotide sequence encoding a cyclic di-nucleotide synthetase enzyme, into the viral genome. The locus may be selected from a group of loci consisting of: gene F13L, gene K1L, viral thymidine kinase gene (TK), and viral ribonucleotide reductase gene (RR). Typically, however, the locus is gene F13L. Accordingly, in one embodiment, the vector further comprises gene F13L. In one embodiment, gene F13L may encode the amino acid sequence represented herein as SEQ ID No: 9, as follows: MWPFAPVPAGAKCRLVETLPENMDFRSDHLTTFECFNEIITLAKKYIYIASFCCNPLSTTRGALIFDKLKEASEKGIKIIVLLDERGKRNLGEL QSHCPDINFITVNIDKKNNVGLLLGCFWVSDNERCYVGNASFTGGSIHTIKTLGVYSDYPPLATDLRRRFDTFKAFNSAKNSWLNLCSAACCLP VSTAYHIKNPIGGVFFTDSPEHLLGYSRDLDTDVVIDKLKSAKTSIDIEHLAIVPTTRVDGNSYYWPDIYNSIIEAAINRGVKIRLLVGNWDKN DVYSMATARSLDALCVQNDLSVKVFTIQNNTKLLIVDDEYVHITSANFDGTHYQNHGFVSFNSIDKQLVSEAKKIFERDWVSSHSKSLKI* [SEQ ID No: 9] In one embodiment, therefore, gene F13L may encode an amino acid sequence substantially as set out in SEQ ID No: 9, or a fragment or variant thereof. In one embodiment, gene F13L may comprise the nucleotide sequence represented herein as SEQ ID No: 10, as follows: ATGTGGCCATTTGCACCGGTACCTGCGGGAGCAAAATGTAGGCTGGTAGAAACACTACCAGAAAATATGGATTTTAGATCCGATCATTTAACAA CATTTGAATGTTTTAACGAAATTATCACTCTAGCTAAGAAATATATATACATAGCATCTTTTTGTTGTAATCCTCTGAGTACGACTAGGGGAGC GCTTATTTTTGATAAACTAAAAGAGGCATCTGAAAAAGGGATTAAAATAATAGTTTTGCTAGATGAACGAGGGAAAAGAAATCTGGGAGAGCTA CAAAGTCACTGCCCGGATATAAATTTTATAACCGTTAATATAGATAAAAAAAATAATGTGGGACTACTACTCGGTTGTTTTTGGGTGTCAGATA ATGAAAGATGTTATGTAGGAAACGCGTCATTTACTGGAGGATCTATACATACGATTAAAACGTTAGGTGTATATTCTGATTATCCCCCGCTGGC CACAGATCTTCGTAGAAGATTTGATACTTTTAAAGCCTTTAATAGCGCAAAAAATTCATGGTTGAATTTATGCTCTGCGGCTTGTTGTCTGCCA GTTAGCACTGCGTATCATATTAAGAATCCTATAGGTGGAGTGTTCTTTACTGATTCTCCGGAACACCTATTGGGATATTCTAGAGATCTAGACA CTGATGTAGTTATTGATAAACTCAAGTCGGCTAAGACTAGTATAGATATTGAACATTTGGCCATAGTTCCCACTACACGTGTCGACGGTAATAG CTACTATTGGCCCGACATTTACAACTCCATTATAGAAGCAGCCATTAATAGAGGAGTTAAGATCAGACTTCTAGTTGGTAATTGGGATAAGAAC GACGTATATTCTATGGCAACCGCCAGAAGTCTAGACGCGTTGTGTGTTCAAAATGATCTATCTGTGAAGGTTTTCACTATTCAGAATAATACAA AATTGTTGATAGTCGACGACGAATATGTTCATATCACTTCGGCAAATTTCGACGGAACCCATTACCAAAATCACGGATTCGTCAGTTTTAATAG TATAGATAAACAGCTTGTAAGCGAGGCTAAAAAAATATTTGAGAGAGATTGGGTATCTAGCCACAGTAAATCGTTAAAAATTTAA [SEQ ID No: 10] In one embodiment, therefore, gene F13L may comprise a nucleotide sequence substantially as set out in SEQ ID No: 10, or a fragment or variant thereof. The inventors have generated embodiments of the vector of the invention comprising the exemplar green fluorescent protein (GFP) gene, as shown in Figure 1. As discussed in Example 1 and as shown in Figure 2, GFP was successfully expressed, allowing for picking of infected cells. As such, the inventors have demonstrated that the vector of the invention can comprise a foreign gene, which encodes a biomolecule other than a cyclic di-nucleotide synthetase enzyme, which may be successfully expressed in an infected host cell. The skilled person would readily appreciate that the GFP is representative of a non-cyclic di-nucleotide synthetase enzyme foreign gene, such as a gene encoding an antigen, because it proves that the vector is able to express, in vitro, another gene harboured on the vector of the invention. As such, the GFP provides robust evidence of the proof of concept that the vector of the invention can be used to express any gene encoding a biomolecule, such as an antigen, in addition to a gene encoding a cyclic di-nucleotide synthetase enzyme. In one embodiment, therefore, the vector may comprise at least one nucleic acid sequence which does not encode a cyclic di-nucleotide synthetase enzyme. Typically, the at least one nucleic acid sequence which does not encode a cyclic di-nucleotide synthetase enzyme encodes at least one biomolecule. Typically, the at least one biomolecule is a therapeutic biomolecule. The at least one therapeutic biomolecule may comprise a therapeutic protein. The skilled person would understand that a therapeutic protein relates to any protein that has therapeutic application, typically in a human. In one embodiment, the therapeutic protein that can be encoded by the at least one nucleic acid sequence may comprise a protein or peptide derived from a pathogen, such as a bacteria, virus, fungus, protozoa, or parasite. The protein or peptide may be an antigen, and therefore one which may stimulate or trigger an immune response in the host. Typically, the protein is an antigen. The protein or peptide derived from a virus may be a viral antigen. The viral antigen may be derived from a virus selected from the group consisting of: Orthomyxoviruses; Paramyxoviridae viruses; Metapneumovirus and Morbilliviruses; Pneumoviruses; Paramyxoviruses; Poxviridae; Metapneumoviruses; Morbilliviruses; Picornaviruses; Enteroviruseses; Bunyaviruses; Phlebovirus; Nairovirus; Heparnaviruses; Togaviruses; Alphavirus; Arterivirus; Flaviviruses; Pestiviruses; Hepadnaviruses; Rhabdoviruses; Caliciviridae; Coronaviruses; Retroviruses; Reoviruses; Parvoviruses; Delta hepatitis virus (HDV); Hepatitis E virus (HEV); Human Herpesviruses and Papovaviruses. The Orthomyxoviruses may be Influenza A, B and C. The Paramyxoviridae virus may be Pneumoviruses (RSV), Paramyxoviruses (PIV). The Metapneumovirus may be Morbilliviruses (e.g., measles). The Pneumovirus may be Respiratory syncytial virus (RSV), Bovine respiratory syncytial virus, Pneumonia virus of mice, or Turkey rhinotracheitis virus. The Paramyxovirus may be Parainfluenza virus types 1 - 4 (PIV), Mumps, Sendai viruses, Simian virus 5, Bovine parainfluenza virus, Nipahvirus, Henipavirus or Newcastle disease virus. The Poxviridae may be Variola vera, for example Variola major and Variola minor. The Metapneumovirus may be human metapneumovirus (hMPV) or avian metapneumoviruses (aMPV). The Morbillivirus may be measles. The Picornaviruses may be Enteroviruses, Rhinoviruses, Heparnavirus, Parechovirus, Cardioviruses and Aphthoviruses. The Enteroviruses may be Poliovirus types 1, 2 or 3, Coxsackie A virus types 1 to 22 and 24, Coxsackie B virus types 1 to 6, Echovirus (ECHO) virus) types 1 to 9, 11 to 27 and 29 to 34 or Enterovirus 68 to 71. The Bunyavirus may be California encephalitis virus. The Phlebovirus may be Rift Valley Fever virus. The Nairovirus may be Crimean-Congo hemorrhagic fever virus. The Heparnaviruses may be Hepatitis A virus (HAV). The Togaviruses may be Rubivirus. The Flavivirus may be Tick-borne encephalitis (TBE) virus, Dengue (types 1, 2, 3 or 4) virus, Yellow Fever virus, Japanese encephalitis virus, Kyasanur Forest Virus, West Nile encephalitis virus, St. Louis encephalitis virus, Russian spring- summer encephalitis virus or Powassan encephalitis virus. The Pestivirus may be Bovine viral diarrhea (BVDV), Classical swine fever (CSFV) or Border disease (BDV). The Hepadnavirus may be Hepatitis B virus or Hepatitis C virus. The Rhabdovirus may be Lyssavirus (Rabies virus) or Vesiculovirus (VSV). The Caliciviridae may be Norwalk virus, or Norwalk-like Viruses, such as Hawaii Virus and Snow Mountain Virus. The Coronavirus may be SARS CoV-1, SARS-CoV-2, MERS, Human respiratory coronavirus, Avian infectious bronchitis (IBV), Mouse hepatitis virus (MHV), or Porcine transmissible gastroenteritis virus (TGEV). The Retrovirus may be Oncovirus, a Lentivirus or a Spumavirus. The Reovirus may be an Orthoreo virus, a Rotavirus, an Orbivirus, or a Coltivirus. The Parvovirus may be Parvovirus B 19. The Human Herpesvirus may be Herpes Simplex Viruses (HSV), Varicella-zoster virus (VZV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Human Herpesvirus 6 (HHV6), Human Herpesvirus 7 (HHV7), or Human Herpesvirus 8 (HHV8). The Papovavirus may be Papilloma viruses, Polyomaviruses, Adenoviruess or Arenaviruses. The protein or peptide derived from bacteria may be a bacterial antigen. The bacterial antigen may derived from a bacterium selected from the group consisting of: Neisseria meningitides, Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, Bordetella pertussis, Burkholderia sp. (e.g., Burkholderia mallei, Burkholderia pseudomallei and Burkholderia cepacia), Staphylococcus aureus, Haemophilus influenzae, Clostridium tetani (Tetanus), Clostridium perfringens, Clostridium botulinums, Cornynebacterium diphtheriae (Diphtheria), Pseudomonas aeruginosa, Legionella pneumophila, Coxiella burnetii, Brucella sp. (e.g., B. abortus, B. canis, B. melitensis, B. neotomae, B. ovis, B. suis and B. pinnipediae, Francisella sp. (e.g., F. novicida, F. philomiragia and F. tularensis), Streptococcus agalactiae, Neiserria gonorrhoeae, Chlamydia trachomatis, Treponema pallidum (Syphilis), Haemophilus ducreyi, Enterococcus faecalis, Enterococcus faecium, Helicobacter pylori, Staphylococcus saprophyticus, Yersinia enter ocolitica, E. coli, Bacillus anthracis (anthrax), Yersinia pestis (plague), Mycobacterium tuberculosis, Rickettsia, Listeria, Chlamydia pneumoniae, Vibrio cholerae, Salmonella typhi (typhoid fever), Borrelia burgdorfer, Porphyromonas s, and Klebsiella sp. The protein or peptide derived from a fungus may be a fungal antigen. The fungal antigen may be derived from a fungus selected from the group consisting of Dermatophytres, including: Epidermophyton koccusum, Microsporum audouini, Microsporum canis, Microsporum distortum, Microsporum equinum, Microsporum gypsum, Microsporum nanum, Trichophyton concentricum, Trichophyton equinum, Trichophyton gallinae, Trichophyton gypseum, Trichophyton megnini, Trichophyton mentagrophytes, Trichophyton quinckeanum, Trichophyton rubrum, Trichophyton schoenleini, Trichophyton tonsurans, Trichophyton verrucosum, T verrucosum var. album, var. discoides, var. ochraceum, Trichophyton violaceum, and / or Trichophyton faviforme; or from Aspergillus fumigatus, Aspergillus kavus, Aspergillus niger, Aspergillus nidulans, Aspergillus terreus, Aspergillus sydowi, Aspergillus kavatus, Aspergillus glaucus, Blastoschizomyces capitatus, Candida albicans, Candida enolase, Candida tropicalis, Candida glabrata, Candida krusei, Candida parapsilosis, Candida stellatoidea, Candida kusei, Candida parakwsei, Candida lusitaniae, Candida pseudotropicalis, Candida guilliermondi, Cladosporium carrionii, Coccidioides immitis, Blastomyces dermatidis, Cryptococcus neoformans, Geotrichum clavatum, Histoplasma capsulatum, Klebsiella pneumoniae, Microsporidia, Encephalitozoon spp., Septata intestinalis and Enterocytozoon bieneusi; Brachiola spp, Microsporidium spp., Nosema spp., Pleistophora spp.,Trachipleistophora spp., Vittaforma spp Paracoccidioides brasiliensis, Pneumocystis carinii, Pythiumn insidiosum, Pityrosporum ovale, Sacharomyces cerevisiae, Saccharomyces boulardii, Saccharomyces pombe, Scedosporium apiosperum, Sporothrix schenckii, Trichosporon beigelii, Toxoplasma gondii, Penicillium marneffei, Malassezia spp., Fonsecaea spp., Wangiella spp., Sporothrix spp., Basidiobolus spp., Conidiobolus spp., Rhizopus spp, Mucor spp, Absidia spp, Mortierella spp, Cunninghamella spp, Saksenaea spp., Alternaria spp, Curvularia spp, Helminthosporium spp, Fusarium spp, Aspergillus spp, Penicillium spp, Monolinia spp, Rhizoctonia spp, Paecilomyces spp, Pithomyces spp, and Cladosporium spp. The protein or peptide derived from a protozoan may be a protozoan antigen. The protozoan antigen may be derived from a protozoan selected from the group consisting of: Entamoeba histolytica, Giardia lambli, Cryptosporidium parvum, Cyclospora cayatanensis and Toxoplasma. The therapeutic biomolecule may be a protein or peptide derived from a plant. Typically, the protein or peptide is a plant antigen. For example, the plant antigen may be derived from Ricinus communis. In another embodiment, the therapeutic biomolecule may be an immunogen or an antigen. Typically, the immunogen or antigen is a tumour immunogen or antigen, or cancer immunogen or antigen. The tumour immunogens and antigens may be peptide- containing tumour antigens, such as a polypeptide tumour antigen or glycoprotein tumour antigens. The tumour antigens may be (a) full length molecules associated with cancer cells, (b) homologs and modified forms of the same, including molecules with deleted, added, and / or substituted portions, and (c) fragments of the same. Suitable tumour immunogens include: class I-restricted antigens recognised by CD8+ lymphocytes or class II-restricted antigens recognised by CD4+ lymphocytes. The tumour antigen may be an antigen that is associated with a cancer selected from the group consisting of: a testis cancer, melanoma, lung cancer, head and neck cancer, NSCLC, breast cancer, gastrointestinal cancer, bladder cancer, colorectal cancer, pancreatic cancer, lymphoma, leukaemia, renal cancer, hepatoma, ovarian cancer, gastric cancer, and prostate cancer. The tumour antigen may be selected from: (a) cancer-testis antigens, such as NY-ESO-I, SSX2, SCP-1, as well as RAGE, BAGE, GAGE and MAGE family polypeptides, for example, GAGE-I, GAGE-2, MAGE-I, MAGE-2, MAGE-3, MAGE-4, MAGE-5, MAGE-6, and MAGE- 12 (which can be used, for example, to address melanoma, lung, head and neck, NSCLC, breast, gastrointestinal, and bladder tumours); (b) mutated antigens, for example, p53 (associated with various solid tumours, e.g., colorectal, lung, head and neck cancer), p21 / Ras (associated with, e.g., melanoma, pancreatic cancer and colorectal cancer), CDK4 (associated with, e.g., melanoma), MUM-1 (associated with, e.g., melanoma), caspase-8 (associated with, e.g., head and neck cancer), CIA 0205 (associated with, e.g., bladder cancer), HLA-A2-R1701, beta catenin (associated with, e.g., melanoma), TCR (associated with, e.g., T- cell non-Hodgkins lymphoma), BCR-abl (associated with, e.g., chronic myelogenous leukemia), triosephosphate isomerase, KIA 0205, CDC-27, and LDLR-FUT; (c) over-expressed antigens, for example, Galectin 4 (associated with, e.g., colorectal cancer), Galectin 9 (associated with, e.g., Hodgkin's disease), proteinase 3 (associated with, e.g., chronic myelogenous leukemia), WT 1 (associated with, e.g., various leukaemias), carbonic anhydrase (associated with, e.g., renal cancer), aldolase A (associated with, e.g., lung cancer), PRAME (associated with, e.g., melanoma), HER-2 / neu (associated with, e.g., breast, colon, lung and ovarian cancer), alpha-fetoprotein (associated with, e.g., hepatoma), KSA (associated with, e.g., colorectal cancer), gastrin (associated with, e.g., pancreatic and gastric cancer), telomerase catalytic protein, MUC-I (associated with, e.g., breast and ovarian cancer), G-250 (associated with, e.g., renal cell carcinoma), p53 (associated with, e.g., breast, colon cancer), and carcinoembryonic antigen (associated with, e.g., breast cancer, lung cancer, and cancers of the gastrointestinal tract such as colorectal cancer); (d) shared antigens, for example, melanoma-melanocyte differentiation antigens, such as MART-1 / Melan A, gp100, MClR, melanocyte-stimulating hormone receptor, tyrosinase, tyrosinase related protein- 1 / TRPl and tyrosinase related protein-2 / TRP2 (associated with, e.g., melanoma); (e) prostate-associated antigens, such as PAP, PSA, PSMA, PSH-Pl, PSM-Pl, PSM-P2, associated with e.g., prostate cancer; and / or (f) immunoglobulin idiotypes (associated with myeloma and B cell lymphomas, for example). As discussed, the inventors have generated various embodiments of the vector of the invention, one of which comprises a copy of the WT cGAS gene (saMVA WT), and another which comprises a catalytically inactive copy of the cGAS gene (cGAS-CI) (saMVA CI). The inventors have also generated a control vector comprising an empty locus (FMVA-Ctrl). In one embodiment, the self-adjuvanting MVA (saMVA WT) vector may comprise the nucleotide sequence represented herein as SEQ ID No: 11, as follows: ctgcagGGCGATGATCTTAATTTTGTGCAATGAGTCGTCAATCCTATAACTTCTAATATTGTAATATTCATCATCGACATAACACTATCTATGT TATCATCGTATATTAGTATACCATGACCTTCTTCATTTCGTGCCAAAATGATATACAGTCTTAAATAGTTACGCAATATCTCAATAGTTTCATA ATTGTTAGCTGTTTTCATCAAGGTTTGTATCCTGTTTAACATGATGGCGTTCTATACGTTTCTATTTTTTAAATTTTTAACGATTTACTGTGGC TAGATACCCAATCTCTCTCAAATATTTTTTTAGCCTCGCTTACAAGCTGTTTATCTATACTATTAAAACTGACGAATCCGTGATTTTGGTAATG GGTTCCGTCGAAATTTGCCGAAGTGATATGAACATATTCGTCGTCGACTATCAACAATTTTGTATTATTCTGAATAGTGAAAACCTTCACAGAT AGATCATTTTGAACACACAACGCGTCTAGACTTCTGGCGGTTGCCATAGAATATACGTCGTTCTTATCCCAATTACCAACTAGAAGTCTGATCT TAACTCCTCTATTAATGGCTGCTTCTATAATGGAGTTGTAAATGTCGGGCCAATAGTAGCTATTACCGTCGACACGTGTAGTGGGAACTATGGC CAAATGTTCAATATCTATACTAGTCTTAGCCGACTTGAGTTTATCAATAACTACATCAGTGTCTAGATCTCTAGAATATCCCAATAGGTGTTCC GGAGAATCAGTAAAGAACACTCCACCTATAGGATTCTTAATATGATACGCAGTGCTAACTGGCAGACAACAAGCCGCAGAGCATAAATTCAACC ATGAATTTTTTGCGCTATTAAAGGCTTTAAAAGTATCAAATCTTCTACGAAGATCTGTGGCCAGCGGGGGATAATCAGAATATACACCTAACGT TTTAATCGTATGTATAGATCCTCCAGTAAATGACGCGTTTCCTACATAACATCTTTCATTATCTGACACCCAAAAACAACCGAGTAGTAGTCCC ACATTATTTTTTTTATCTATATTAACGGTTATAAAATTTATATCCGGGCAGTGACTTTGTAGCTCTCCCAGATTTCTTTTCCCTCGTTCATCTA GCAAAACTATTATTTTAATCCCTTTTTCAGATGCCTCTTTTAGTTTATCAAAAATAAGCGCTCCCCTAGTCGTACTCAGAGGATTACAACAAAA AGATGCTATGTATATATATTTCTTAGCTAGAGTGATAATTTCGTTAAAACATTCAAATGTTGTTAAATGATCGGATCTAAAATCCATATTTTCT GGTAGTGTTTCTACCAGCCTACATTTTGCTCCCGCAGGTACCGGTGCAAATGGCCACATTTAGTTAACATAAAAACTCCAAACCCACCCGCTTT TTATAGTAAGTTTTTCACCCATAAATAATAAATACAATAATTAATTTCTCGTAAAAGTAGAAAATATATTCTAATTTATTGCACGGTAAGGAAG TAGATCCCTATCAGTGATAGAGAATTCCCTATCAGTGATAGAGAGGATCCATGCAACCATGGCATGGAAAGGCTATGCAAAGAGCTTCTGAAGC GGGAGCTACAGCTCCAAAAGCTTCTGCTAGAAATGCTAGAGGTGCTCCAATGGACCCAACAGAATCTCCAGCTGCTCCAGAAGCTGCTTTACCA AAAGCGGGAAAATTTGGACCGGCGAGAAAGTCTGGATCGAGACAAAAAAAGTCTGCGCCGGACACACAAGAAAGACCACCAGTTAGAGCTACAG GTGCCAGAGCTAAAAAAGCTCCACAAAGAGCGCAAGATACCCAACCATCTGATGCTACATCTGCTCCAGGTGCTGAAGGATTAGAACCACCAGC TGCTAGAGAACCAGCTCTATCAAGAGCTGGATCTTGCAGACAAAGAGGTGCTAGATGTTCCACAAAACCTAGACCACCACCAGGACCATGGGAT GTACCAAGTCCAGGATTACCAGTATCTGCGCCGATCCTAGTTAGAAGAGATGCTGCTCCTGGTGCCTCTAAACTAAGAGCGGTACTAGAGAAGC TAAAGCTATCCAGAGATGACATCTCCACAGCTGCCGGAATGGTTAAGGGTGTAGTAGACCACCTACTACTAAGATTGAAGTGCGACTCTGCGTT CAGAGGTGTCGGACTATTGAACACCGGATCTTACTACGAGCACGTCAAAATCTCTGCCCCGAACGAATTCGACGTCATGTTCAAACTAGAGGTC CCGAGAATCCAGCTAGAGGAATACTCTAACACCAGAGCGTACTACTTCGTCAAGTTCAAGAGAAACCCGAAAGAGAACCCGCTATCGCAATTTT TGGAGGGAGAAATCCTATCCGCGTCCAAGATGCTATCCAAGTTCAGAAAGATCATCAAAGAAGAGATCAACGACATCAAGGACACCGACGTCAT CATGAAGAGAAAGAGAGGTGGAAGTCCGGCGGTCACACTACTAATCTCTGAAAAGATCTCCGTCGACATCACCCTAGCGTTGGAGTCTAAATCT TCTTGGCCAGCGTCTACCCAAGAGGGACTAAGAATCCAAAATTGGCTATCCGCGAAAGTCAGAAAGCAGTTGAGATTGAAGCCGTTCTACTTGG TCCCGAAGCACGCTAAAGAAGGAAACGGATTCCAAGAAGAGACTTGGAGACTATCGTTCTCCCACATCGAGAAAGAAATCTTGAACAACCACGG AAAGTCCAAGACCTGCTGCGAGAACAAAGAGGAAAAGTGCTGTAGAAAGGACTGCCTAAAGCTAATGAAGTACCTACTAGAGCAGTTGAAAGAG AGATTCAAGGACAAGAAGCACCTAGACAAGTTCTCGTCCTACCACGTAAAGACCGCCTTTTTCCATGTCTGTACACAGAACCCGCAAGACTCTC AGTGGGACAGAAAAGATTTGGGACTATGCTTCGACAACTGCGTGACCTACTTCCTACAGTGTCTAAGAACCGAGAAGTTGGAGAACTACTTCAT CCCCGAGTTCAACCTATTCTCCTCCAACCTAATCGACAAGAGATCCAAAGAGTTCTTGACCAAGCAGATCGAGTACGAGAGAAACAACGAGTTC CCGGTGTTCGATGAATTTGCGGCCGCAGATTACAAGGATGATGACGACAAGGACTACAAGGACGACGATGATAAGGATTATAAGGACGATGATG ACAAATAGTCTAGACTCGAGTTACCCGATTGTAGTTAAGTTTTGAATAAAATTTTTTATAATAAATGGTGAGCAAaGGCGAGGAGCTtTTCACC GGGGTGGTGCCgATCCTGGTCGAaCTGGACGGCGACGTgAACGGCCACAAGTTtAGCGTGTCCGGaGAGGGCGAGGGCGAcGCCACCTACGGCA AaCTGACCCTtAAGTTCATCTGCACCACgGGCAAGCTGCCCGTtCCCTGGCCCACCCTgGTGACCACCCTGACCTAtGGCGTGCAGTGCTTtAG CCGCTACCCCGACCAtATGAAGCAaCACGACTTCTTCAAaTCCGCCATGCCCGAgGGCTACGTCCAGGAGCGgACCATCTTCTTCAAaGACGAC GGCAAtTACAAGACCCGCGCgGAGGTGAAGTTCGAGGGgGACACCCTGGTGAACCGgATCGAGCTGAAGGGgATCGACTTCAAGGAGGACGGgA ACATCCTGGGcCACAAGCTGGAGTACAACTAtAACAGCCACAACGTCTAcATCATGGCCGACAAGCAaAAGAACGGCATCAAGGTcAACTTCAA GATCCGgCACAACATCGAGGACGGgAGCGTGCAGCTCGCgGACCACTACCAaCAGAACACCCCgATCGGCGACGGCCCgGTGCTGCTGCCgGAC AACCACTACCTcAGCACCCAGTCCGCgCTGAGCAAAGACCCgAACGAGAAGCGCGAcCACATGGTCCTGCTGGAaTTCGTGACCGCgGCCGGGA TCACgCTCGGCATGGAtGAGCTGTACAAGTAgAAAATATTAAAAAAAAATACTTTTTTTATTAAgatatcTTAGTTAACATAAAAACTTATACA TCCTGTTCTATCAACGATTCTAGAATATCATCGGCTATATCGCTAAAATTTTCATCAAAGTCGACATCACAACCTAACTCAGTCAATATATTAA GAAGTTCCATGATGTCATCTTCGTCTATTTCTATATCCGTATCCATTGTAGATTGTTGACCGATTATCGAGTTTAAATCATTACTAATACTCAA TCCTTCAGAATACAATCTGTGTTTCATTGTAAATTTATgagctc [SEQ ID No: 11] In one embodiment, therefore, the recombinant vector may comprise a nucleic acid sequence substantially as set out in SEQ ID No: 11, or a fragment or variant thereof. In one embodiment, the catalytically inactive self-adjuvanting MVA (saMVA CI) vector may comprise the nucleotide sequence represented herein as SEQ ID No: 12, as follows: ctgcagGGCGATGATCTTAATTTTGTGCAATGAGTCGTCAATCCTATAACTTCTAATATTGTAATATTCATCATCGACATAACACTATCTATGT TATCATCGTATATTAGTATACCATGACCTTCTTCATTTCGTGCCAAAATGATATACAGTCTTAAATAGTTACGCAATATCTCAATAGTTTCATA ATTGTTAGCTGTTTTCATCAAGGTTTGTATCCTGTTTAACATGATGGCGTTCTATACGTTTCTATTTTTTAAATTTTTAACGATTTACTGTGGC TAGATACCCAATCTCTCTCAAATATTTTTTTAGCCTCGCTTACAAGCTGTTTATCTATACTATTAAAACTGACGAATCCGTGATTTTGGTAATG GGTTCCGTCGAAATTTGCCGAAGTGATATGAACATATTCGTCGTCGACTATCAACAATTTTGTATTATTCTGAATAGTGAAAACCTTCACAGAT AGATCATTTTGAACACACAACGCGTCTAGACTTCTGGCGGTTGCCATAGAATATACGTCGTTCTTATCCCAATTACCAACTAGAAGTCTGATCT TAACTCCTCTATTAATGGCTGCTTCTATAATGGAGTTGTAAATGTCGGGCCAATAGTAGCTATTACCGTCGACACGTGTAGTGGGAACTATGGC CAAATGTTCAATATCTATACTAGTCTTAGCCGACTTGAGTTTATCAATAACTACATCAGTGTCTAGATCTCTAGAATATCCCAATAGGTGTTCC GGAGAATCAGTAAAGAACACTCCACCTATAGGATTCTTAATATGATACGCAGTGCTAACTGGCAGACAACAAGCCGCAGAGCATAAATTCAACC ATGAATTTTTTGCGCTATTAAAGGCTTTAAAAGTATCAAATCTTCTACGAAGATCTGTGGCCAGCGGGGGATAATCAGAATATACACCTAACGT TTTAATCGTATGTATAGATCCTCCAGTAAATGACGCGTTTCCTACATAACATCTTTCATTATCTGACACCCAAAAACAACCGAGTAGTAGTCCC ACATTATTTTTTTTATCTATATTAACGGTTATAAAATTTATATCCGGGCAGTGACTTTGTAGCTCTCCCAGATTTCTTTTCCCTCGTTCATCTA GCAAAACTATTATTTTAATCCCTTTTTCAGATGCCTCTTTTAGTTTATCAAAAATAAGCGCTCCCCTAGTCGTACTCAGAGGATTACAACAAAA AGATGCTATGTATATATATTTCTTAGCTAGAGTGATAATTTCGTTAAAACATTCAAATGTTGTTAAATGATCGGATCTAAAATCCATATTTTCT GGTAGTGTTTCTACCAGCCTACATTTTGCTCCCGCAGGTACCGGTGCAAATGGCCACATTTAGTTAACATAAAAACTCCAAACCCACCCGCTTT TTATAGTAAGTTTTTCACCCATAAATAATAAATACAATAATTAATTTCTCGTAAAAGTAGAAAATATATTCTAATTTATTGCACGGTAAGGAAG TAGATCCCTATCAGTGATAGAGAATTCCCTATCAGTGATAGAGAGGATCCATGCAACCATGGCATGGAAAGGCTATGCAAAGAGCTTCTGAAGC GGGAGCTACAGCTCCAAAAGCTTCTGCTAGAAATGCTAGAGGTGCTCCAATGGACCCAACAGAATCTCCAGCTGCTCCAGAAGCTGCTTTACCA AAAGCGGGAAAATTTGGACCGGCGAGAAAGTCTGGATCGAGACAAAAAAAGTCTGCGCCGGACACACAAGAAAGACCACCAGTTAGAGCTACAG GTGCCAGAGCTAAAAAAGCTCCACAAAGAGCGCAAGATACCCAACCATCTGATGCTACATCTGCTCCAGGTGCTGAAGGATTAGAACCACCAGC TGCTAGAGAACCAGCTCTATCAAGAGCTGGATCTTGCAGACAAAGAGGTGCTAGATGTTCCACAAAACCTAGACCACCACCAGGACCATGGGAT GTACCAAGTCCAGGATTACCAGTATCTGCGCCGATCCTAGTTAGAAGAGATGCTGCTCCTGGTGCCTCTAAACTAAGAGCGGTACTAGAGAAGC TAAAGCTATCCAGAGATGACATCTCCACAGCTGCCGGAATGGTTAAGGGTGTAGTAGACCACCTACTACTAAGATTGAAGTGCGACTCTGCGTT CAGAGGTGTCGGACTATTGAACACCGGATCTTACTACGAGCACGTCAAAATCTCTGCCCCGAACGcATTCGcCGTCATGTTCAAACTAGAGGTC CCGAGAATCCAGCTAGAGGAATACTCTAACACCAGAGCGTACTACTTCGTCAAGTTCAAGAGAAACCCGAAAGAGAACCCGCTATCGCAATTTT TGGAGGGAGAAATCCTATCCGCGTCCAAGATGCTATCCAAGTTCAGAAAGATCATCAAAGAAGAGATCAACGACATCAAGGACACCGACGTCAT CATGAAGAGAAAGAGAGGTGGAAGTCCGGCGGTCACACTACTAATCTCTGAAAAGATCTCCGTCGACATCACCCTAGCGTTGGAGTCTAAATCT TCTTGGCCAGCGTCTACCCAAGAGGGACTAAGAATCCAAAATTGGCTATCCGCGAAAGTCAGAAAGCAGTTGAGATTGAAGCCGTTCTACTTGG TCCCGAAGCACGCTAAAGAAGGAAACGGATTCCAAGAAGAGACTTGGAGACTATCGTTCTCCCACATCGAGAAAGAAATCTTGAACAACCACGG AAAGTCCAAGACCTGCTGCGAGAACAAAGAGGAAAAGTGCTGTAGAAAGGACTGCCTAAAGCTAATGAAGTACCTACTAGAGCAGTTGAAAGAG AGATTCAAGGACAAGAAGCACCTAGACAAGTTCTCGTCCTACCACGTAAAGACCGCCTTTTTCCATGTCTGTACACAGAACCCGCAAGACTCTC AGTGGGACAGAAAAGATTTGGGACTATGCTTCGACAACTGCGTGACCTACTTCCTACAGTGTCTAAGAACCGAGAAGTTGGAGAACTACTTCAT CCCCGAGTTCAACCTATTCTCCTCCAACCTAATCGACAAGAGATCCAAAGAGTTCTTGACCAAGCAGATCGAGTACGAGAGAAACAACGAGTTC CCGGTGTTCGATGAATTTGCGGCCGCAGATTACAAGGATGATGACGACAAGGACTACAAGGACGACGATGATAAGGATTATAAGGACGATGATG ACAAATAGTCTAGACTCGAGTTACCCGATTGTAGTTAAGTTTTGAATAAAATTTTTTATAATAAATGGTGAGCAAaGGCGAGGAGCTtTTCACC GGGGTGGTGCCgATCCTGGTCGAaCTGGACGGCGACGTgAACGGCCACAAGTTtAGCGTGTCCGGaGAGGGCGAGGGCGAcGCCACCTACGGCA AaCTGACCCTtAAGTTCATCTGCACCACgGGCAAGCTGCCCGTtCCCTGGCCCACCCTgGTGACCACCCTGACCTAtGGCGTGCAGTGCTTtAG CCGCTACCCCGACCAtATGAAGCAaCACGACTTCTTCAAaTCCGCCATGCCCGAgGGCTACGTCCAGGAGCGgACCATCTTCTTCAAaGACGAC GGCAAtTACAAGACCCGCGCgGAGGTGAAGTTCGAGGGgGACACCCTGGTGAACCGgATCGAGCTGAAGGGgATCGACTTCAAGGAGGACGGgA ACATCCTGGGcCACAAGCTGGAGTACAACTAtAACAGCCACAACGTCTAcATCATGGCCGACAAGCAaAAGAACGGCATCAAGGTcAACTTCAA GATCCGgCACAACATCGAGGACGGgAGCGTGCAGCTCGCgGACCACTACCAaCAGAACACCCCgATCGGCGACGGCCCgGTGCTGCTGCCgGAC AACCACTACCTcAGCACCCAGTCCGCgCTGAGCAAAGACCCgAACGAGAAGCGCGAcCACATGGTCCTGCTGGAaTTCGTGACCGCgGCCGGGA TCACgCTCGGCATGGAtGAGCTGTACAAGTAgAAAATATTAAAAAAAAATACTTTTTTTATTAAgatatcTTAGTTAACATAAAAACTTATACA TCCTGTTCTATCAACGATTCTAGAATATCATCGGCTATATCGCTAAAATTTTCATCAAAGTCGACATCACAACCTAACTCAGTCAATATATTAA GAAGTTCCATGATGTCATCTTCGTCTATTTCTATATCCGTATCCATTGTAGATTGTTGACCGATTATCGAGTTTAAATCATTACTAATACTCAA TCCTTCAGAATACAATCTGTGTTTCATTGTAAATTTATgagctc [SEQ ID No: 12] In one embodiment, therefore, the recombinant vector may comprise a nucleic acid sequence substantially as set out in SEQ ID No: 12, or a fragment or variant thereof. In one embodiment, the control MVA (FMVA-Ctrl) vector may comprise the nucleotide sequence represented herein as SEQ ID No: 13, as follows: ctgcagGGCGATGATCTTAATTTTGTGCAATGAGTCGTCAATCCTATAACTTCTAATATTGTAATATTCATCATCGACATAACACTATCTATGT TATCATCGTATATTAGTATACCATGACCTTCTTCATTTCGTGCCAAAATGATATACAGTCTTAAATAGTTACGCAATATCTCAATAGTTTCATA ATTGTTAGCTGTTTTCATCAAGGTTTGTATCCTGTTTAACATGATGGCGTTCTATACGTTTCTATTTTTTAAATTTTTAACGATTTACTGTGGC TAGATACCCAATCTCTCTCAAATATTTTTTTAGCCTCGCTTACAAGCTGTTTATCTATACTATTAAAACTGACGAATCCGTGATTTTGGTAATG GGTTCCGTCGAAATTTGCCGAAGTGATATGAACATATTCGTCGTCGACTATCAACAATTTTGTATTATTCTGAATAGTGAAAACCTTCACAGAT AGATCATTTTGAACACACAACGCGTCTAGACTTCTGGCGGTTGCCATAGAATATACGTCGTTCTTATCCCAATTACCAACTAGAAGTCTGATCT TAACTCCTCTATTAATGGCTGCTTCTATAATGGAGTTGTAAATGTCGGGCCAATAGTAGCTATTACCGTCGACACGTGTAGTGGGAACTATGGC CAAATGTTCAATATCTATACTAGTCTTAGCCGACTTGAGTTTATCAATAACTACATCAGTGTCTAGATCTCTAGAATATCCCAATAGGTGTTCC GGAGAATCAGTAAAGAACACTCCACCTATAGGATTCTTAATATGATACGCAGTGCTAACTGGCAGACAACAAGCCGCAGAGCATAAATTCAACC ATGAATTTTTTGCGCTATTAAAGGCTTTAAAAGTATCAAATCTTCTACGAAGATCTGTGGCCAGCGGGGGATAATCAGAATATACACCTAACGT TTTAATCGTATGTATAGATCCTCCAGTAAATGACGCGTTTCCTACATAACATCTTTCATTATCTGACACCCAAAAACAACCGAGTAGTAGTCCC ACATTATTTTTTTTATCTATATTAACGGTTATAAAATTTATATCCGGGCAGTGACTTTGTAGCTCTCCCAGATTTCTTTTCCCTCGTTCATCTA GCAAAACTATTATTTTAATCCCTTTTTCAGATGCCTCTTTTAGTTTATCAAAAATAAGCGCTCCCCTAGTCGTACTCAGAGGATTACAACAAAA AGATGCTATGTATATATATTTCTTAGCTAGAGTGATAATTTCGTTAAAACATTCAAATGTTGTTAAATGATCGGATCTAAAATCCATATTTTCT GGTAGTGTTTCTACCAGCCTACATTTTGCTCCCGCAGGTACCGGTGCAAATGGCCACATTTAGTTAACATAAAAACTCCAAACCCACCCGCTTT TTATAGTAAGTTTTTCACCCATAAATAATAAATACAATAATTAATTTCTCGTAAAAGTAGAAAATATATTCTAATTTATTGCACGGTAAGGAAG TAGATCCCTATCAGTGATAGAGAATTCCCTATCAGTGATAGAGAGGATCCATCGTGCACTCGAGTTACCCGATTGTAGTTAAGTTTTGAATAAA ATTTTTTATAATAAATGGTGAGCAAaGGCGAGGAGCTtTTCACCGGGGTGGTGCCgATCCTGGTCGAaCTGGACGGCGACGTgAACGGCCACAA GTTtAGCGTGTCCGGaGAGGGCGAGGGCGAcGCCACCTACGGCAAaCTGACCCTtAAGTTCATCTGCACCACgGGCAAGCTGCCCGTtCCCTGG CCCACCCTgGTGACCACCCTGACCTAtGGCGTGCAGTGCTTtAGCCGCTACCCCGACCAtATGAAGCAaCACGACTTCTTCAAaTCCGCCATGC CCGAgGGCTACGTCCAGGAGCGgACCATCTTCTTCAAaGACGACGGCAAtTACAAGACCCGCGCgGAGGTGAAGTTCGAGGGgGACACCCTGGT GAACCGgATCGAGCTGAAGGGgATCGACTTCAAGGAGGACGGgAACATCCTGGGcCACAAGCTGGAGTACAACTAtAACAGCCACAACGTCTAc ATCATGGCCGACAAGCAaAAGAACGGCATCAAGGTcAACTTCAAGATCCGgCACAACATCGAGGACGGgAGCGTGCAGCTCGCgGACCACTACC AaCAGAACACCCCgATCGGCGACGGCCCgGTGCTGCTGCCgGACAACCACTACCTcAGCACCCAGTCCGCgCTGAGCAAAGACCCgAACGAGAA GCGCGAcCACATGGTCCTGCTGGAaTTCGTGACCGCgGCCGGGATCACgCTCGGCATGGAtGAGCTGTACAAGTAgAAAATATTAAAAAAAAAT ACTTTTTTTATTAAgatatcTTAGTTAACATAAAAACTTATACATCCTGTTCTATCAACGATTCTAGAATATCATCGGCTATATCGCTAAAATT TTCATCAAAGTCGACATCACAACCTAACTCAGTCAATATATTAAGAAGTTCCATGATGTCATCTTCGTCTATTTCTATATCCGTATCCATTGTA GATTGTTGACCGATTATCGAGTTTAAATCATTACTAATACTCAATCCTTCAGAATACAATCTGTGTTTCATTGTAAATTTATgagctc [SEQ ID No: 13] In one embodiment, therefore, the control vector may comprise a nucleic acid sequence substantially as set out in SEQ ID No: 13, or a fragment or variant thereof. The mammalian pattern recognition receptor (PRR) (e.g., cyclic GTP-ATP synthase (cGAS)) detects double stranded DNA (dsDNA) in the cytoplasm and induces antiviral signalling via production of the secondary messenger 2’3’-cyclic GMP-AMP (2’3’-cGAMP). Activation of cGAS thus depends on the presence of dsDNA in the cytosol. However, this is a limitation, because in resting eukaryotic cells dsDNA is not in the cytosol, but is instead contained within the nucleus and, to a much lower extent, other organelles. The present disclosure provides a strategy of delivering the PRR (e.g., cGAS) and the dsDNA (i.e., viral genome) to the same cell to result in immediate activation of the sensor, production of endogenous natural adjuvants (e.g., 2’3’-cGAMP), and induction of signalling downstream of STING. As a consequence, the vector according to the invention results in higher production of interferons and immune cytokines and enhanced immunogenicity. Accordingly, in one embodiment, the at least one cyclic di-nucleotide synthetase enzyme detects and / or binds DNA. In one embodiment, the at least one cyclic di-nucleotide synthetase enzyme detects and / or binds double stranded DNA (dsDNA). In one embodiment, the dsDNA may be located in the cytoplasm and / or nucleus. Typically, however, the dsDNA is located in the cytoplasm. In one embodiment, therefore, the at least one cyclic di-nucleotide synthetase enzyme detects and / or binds dsDNA in the cytoplasm. In one embodiment, the dsDNA may originate from the vector of the invention. In another embodiment, the dsDNA may originate from the host cell. The dsDNA originating from the host cell may originate from the nucleus or an organelle of the host cell. Accordingly, the dsDNA may comprise mitochondrial DNA (mtDNA). It will be appreciated that cells release nuclear and / or organelle DNA as part of a stress response, for example a stress response to infection. Typically, however, the dsDNA is located in the cytoplasm. Typically, the dsDNA is delivered by the vector. In one embodiment, therefore, the at least one cyclic di- nucleotide synthetase enzyme detects and / or binds dsDNA in the cytoplasm. In another embodiment, the at least one cyclic di-nucleotide synthetase enzyme produces a second messenger upon binding to dsDNA. In one embodiment, the vector may increase the production of a second messenger. The second messenger may be immunogenic. The second messenger may have adjuvanting properties. It will be appreciated that the term “adjuvanting properties” can mean that the second messenger increases the efficacy and / or potency of an immune response. In one embodiment, the second messenger may be selected from a group consisting of: 2′3′ cyclic GMP–AMP (cGAMP), cyclic AMP, cyclic GMP, inositol triphosphate, diacylglycerol, and calcium. In one embodiment, however, the second messenger is 2′3′ cyclic GMP–AMP (cGAMP). In another embodiment, the vector may activate a signalling pathway. The signalling pathway may comprise the cGAS-STING signalling pathway, the JAK-STAT signalling pathway, the RIG-I like receptor signalling pathway, and / or the TNF signalling pathway. The inventors have shown that embodiments of the vector of the invention induce an enhanced T cell response in vivo compared to a control vector which doesn’t comprise a molecular adjuvant. In addition, the inventors have shown that an embodiment of the vector of the invention induces greater transcription of type I and type III interferon compared to a control vector which doesn’t comprise a molecular adjuvant. In another embodiment, therefore, the vector may increase the production of an immune mediator. It will be appreciated that the term “immune mediator” can mean any molecule, cell, or component of the immune system that plays a role in regulating or mediating an immune response. The immune mediator may comprise a cytokine, chemokine, interferon, or interleukin. Typically, however, the cytokine, chemokine, interferon, interleukin, or innate signalling factor comprises type I, type II, or type III interferons, interferon-stimulated genes (ISGs) such as IFIT1, JAKs, IRFs, OA, and cytokines such as CXCL10, CCL5, IL-12, TNF, IL-8, and CXCL8. In another embodiment, the vector may increase a T cell response. In another embodiment, the protein product may induce antiviral signalling. The antiviral signalling may comprise STING, MAVS, IRFs, IKKs, MAPKs, JAKs, and / or STATs. The protein product may induce antiviral signalling via the production of a second messenger. Typically, however, the protein product induces antiviral signalling via production of 2’3’-cyclic GMP-AMP (2’3’-cGAMP). The inventors discovered that embodiments of the vector of the invention induce signalling not only directly infected cells, but also in bystander cells, via transport of 2’3’- cGAMP. In one embodiment, therefore, the vector may increase the production of a second messenger, activate a signalling pathway, increase the production of an immune mediator, and / or increase a T cell response, in a directly infected cell and / or in a bystander cell. It will be appreciated that the term “directly infected cell” can mean a cell which is infected by the viral vector. It will also be appreciated that the term “bystander cell” can mean a cell which is not infected by the viral vector. The bystander cell may be adjacent to or surround the directly infected cell. It will be appreciated that the second messenger, activate a signalling pathway, increase the production of an immune mediator, and / or increase a T cell response may be further defined as disclosed above. The inventors believe that their recombinant vector provides a platform to effectively improve an immune response induced upon vaccination. As such, the inventors envisage the use of their vector in a vaccine. Accordingly, in a second aspect of the invention, there is provided a vaccine comprising the recombinant vector according to the first aspect. According to a third aspect of the invention, there is provided the recombinant vector according to the first aspect, or the vaccine according to the second aspect, for use in therapy. In a fourth aspect of the invention, there is provided the recombinant vector according to the first aspect, or the vaccine according to the second aspect, for use in inducing or enhancing an immune response in a subject. In a fifth aspect, there is provided a method of inducing or enhancing an immune response in a subject, the method comprising administering, or having administered, to the subject in need of such treatment, a therapeutically effective amount of the recombinant vector according to the first aspect, or the vaccine according to the second aspect. In a sixth aspect of the invention, there is provided the recombinant vector according to the first aspect, or the vaccine according to the second aspect, for use in treating, preventing, or ameliorating an infectious disease or cancer. According to a seventh aspect of the invention, there is provided a method of treating, preventing, or ameliorating an infectious disease or cancer in a subject, the method comprising administering, or having administered, to the subject in need of such treatment, a therapeutically effective amount of the recombinant vector according to the first aspect, or the vaccine according to the second aspect. The infectious disease may be a viral, bacterial, fungal, or protozoan infectious disease. The viral infectious disease may be caused by a pathogenic member of the orthopoxvirus (OXPV) genus, monkeypox virus (MPXV), vanilla virus (VARV), or ebolavirus (EBOV). The viral infectious disease may be selected from a group of viral infectious diseases consisting of: gastroenteritis, keratoconjunctivitis, pharyngitis, pharyngoconjunctival fever, hand, foot and mouth disease, pleurodynia, aseptic meningitis, pericarditis, myocarditis, infectious mononucleosis, cytomegalic inclusion disease, liver, lung and spleen disease, infectious mononucleosis, Burkitt's lymphoma, Hodgkin's lymphoma nasopharyngeal carcinoma, acute hepatitis, chronic hepatitis, hepatic cirrhosis, hepatocellular carcinoma, herpes labialis, cold sores, gingivostomatitis, tonsillitis, pharyngitis, keratoconjunctivitis, skin vesicles, mucosal ulcers, AIDS, common cold, pneumonia, bronchiolitis, rhinitis, bronchitis, croup, Kaposi sarcoma, multicentric Castleman disease, primary effusion lymphoma, common, flat, plantar and anogenital warts, laryngeal papillomas, epidermodysplasia verruciformis, cervical carcinoma, squamous cell carcinomas, influenza, Reye syndrome, measles, postinfectious encephalomyelitis, Middle East respiratory syndrome (MERS), mumps, poliomyelitis, rabies, influenza-like syndrome, congenital rubella, German measles, severe acute respiratory syndrome (SARS), coronavirus disease 2019 (COVID-19), chickenpox, herpes zoster, and Congenital varicella syndrome. The bacterial infectious disease may be selected from a group of bacterial infectious diseases consisting of: Meningitis, Tuberculosis, Chlamydia, Leptospirosis, Pneumonia, Tetanus, Cellulitis, Cholera, Pseudomonas infection, Strep throat, urinary tract infection, Legionnaires’ disease, Q fever, whooping cough (pertussis), Anthrax, Leptospirosis, Botulism, Diptheria, Gonorrhea, Lyme diseae, Syphilis, and Salmonella. The fungal infectious disease may be selected from a group of fungal infectious diseases consisting of: Aspergillosis, Basidiobolomycosis, Blastomycosis, Candidosis, Chromoblastomycosis, Coccidioidomycosis, Conidiobolomycosis, Cryptococcosis, Dermatophytosis, Eumycetoma, Histoplasmosis, Lobomycosis, Mucormycosis, Non- dermatophyte superficial dermatomycoses, Paracoccidioidomycosis, Phaeohyphomycosis, Pneumocystosis, Scedosporiosis, Sporotrichosis, Talaromycosis, and Emmonsiosis. The cancer may be selected from a group of cancers consisting of: testis cancer, melanoma, lung cancer, head and neck cancer, lung cancer, breast cancer, gastrointestinal cancer, bladder cancer, colorectal cancer, pancreatic cancer, lymphoma, leukaemia, multiple myeloma, renal cancer, hepatic cancer, ovarian cancer, gastric cancer, brain cancer, and prostate cancer. In one embodiment, the immune response may comprise the innate immune response, the adaptive immune response, or the humoral immune response. Typically, the immune response comprises the innate immune response and / or the adaptive immune response. More typically, however, the immune response comprises the innate immune response and the adaptive immune response. In another embodiment, the recombinant vector according to the first aspect, or the vaccine according to the second aspect, increases levels of a second messenger in the subject. In another embodiment, the recombinant vector according to the first aspect, or the vaccine according to the second aspect, increases levels of cytokines and / or chemokines in the subject. In an eighth aspect of the invention, there is provided a pharmaceutical composition comprising the recombinant vector according to the first aspect, or the vaccine according to the second aspect, and a pharmaceutically acceptable excipient. The invention also provides, in a ninth aspect, a process for making the pharmaceutical composition according to the eighth aspect, the process comprising combining a therapeutically effective amount of the vector according to the first aspect, or the vaccine according to the second aspect, and a pharmaceutically acceptable vehicle. It will be appreciated that the vector, pharmaceutical composition, or vaccine according to the invention may be used in a monotherapy (e.g., the use of the vector, pharmaceutical composition, or vaccine alone), for therapy, typically for use in immunotherapy; or in combination with known immunotherapies, i.e., in a combined therapy. For example, the inventors believe that the vector, pharmaceutical composition, or vaccine of the invention may be used in conjunction with other therapeutic modalities, such as anti-inflammatories, corticosteroids, or immunosuppressants, to promote and / or enhance immune activation. The vector, pharmaceutical composition, or vaccine according to the invention may comprise a number of different forms depending, in particular, on the manner in which the composition is to be used. Thus, for example, the composition may be in the form of a liquid, typically delivered intravenously to a person in need of treatment. It will be appreciated that the vehicle of medicaments according to the invention should be one which is well-tolerated by the subject to whom it is given. Medicaments comprising the vector of the invention may be used in a number of ways. For instance, oral administration may be required, in which case the agents may be contained within a composition that may, for example, be ingested orally in the form of a tablet, capsule or liquid. Compositions comprising agents and medicaments of the invention may be administered by inhalation (e.g., intranasally). Compositions may also be formulated for topical use. For instance, creams or ointments may be applied to the skin. The recombinant vector of the invention may also be incorporated within a slow- or delayed-release device. Such devices may, for example, be inserted on or under the skin, and the medicament may be released over weeks or even months. The device may be located at least adjacent the treatment site. Such devices may be particularly advantageous when long-term treatment with the recombinant vector is required, and which would normally require frequent administration (e.g., at least daily injection). In one embodiment, agents and medicaments according to the invention may be administered to a subject by injection into the blood stream or directly into a site requiring treatment. Injections may be intravenous (bolus or infusion) or subcutaneous (bolus or infusion), or intradermal (bolus or infusion). It will be appreciated that the amount of the vector, pharmaceutical composition, or vaccine that is required is determined by its biological activity and bioavailability, which in turn depends on the mode of administration, the physiochemical properties of the agent, and whether it is being used as a monotherapy or in a combined therapy. The frequency of administration will also be influenced by the in vivo persistence of the vector, pharmaceutical composition, or vaccine within the subject being treated. Optimal dosages to be administered may be determined by those skilled in the art, and will vary with the particular agent in use, the strength of the pharmaceutical composition or vaccine, the mode of administration, and the advancement of the disease being treated. Additional factors depending on the particular subject being treated will result in a need to adjust dosages, including subject age, weight, gender, diet, and time of administration. Generally, a daily dose of between 0.001µg / kg of body weight and 100mg / kg of body weight of the recombinant vector of the invention may be used for the immunisation, depending upon the agent used. In some embodiments, the daily dose of agent is between 1µg / kg of body weight and 100mg / kg of body weight, or between 10µg / kg and 10mg / kg body weight, or between approximately 100µg / kg and 10mg / kg body weight. Daily doses may be given as a single administration (e.g., a single daily injection). Alternatively, the recombinant vector may require administration twice or more times during a day. As an example, the recombinant vector may be administered as an initial primer and a subsequent boost(s), or two boosts administered at between a week or monthly intervals. In some embodiments, the recombinant vector may be administered as an initial primer and a subsequent boost, administered between two to six weeks apart. Known procedures, such as those conventionally employed by the pharmaceutical industry (e.g., in vivo experimentation, clinical trials, etc.), may be used to form specific formulations of the recombinant vector according to the invention and precise therapeutic regimes (such as daily doses of the agents and the frequency of administration). A “subject” may be a vertebrate, mammal, or domestic animal. Hence, compositions and medicaments according to the invention may be used to treat any mammal, for example livestock (e.g., a horse), pets, or may be used in other veterinary applications. Most typically, the subject is a human being. A “therapeutically effective amount” of the vector, pharmaceutical composition, or vaccine is any amount which, when administered to a subject, is the amount of agent that is needed to treat the disease being treated, or produce the desired effect. For example, the therapeutically effective amount of the vector used may be at least 5 × 101, 5 × 102, or 5 × 103vectors. Typically, at least 5 × 104, or at least 5 × 105, or at least 5 × 106, or at least 5 x 107vectors are used. A “pharmaceutically acceptable vehicle” as referred to herein, is any known compound or combination of known compounds that are known to those skilled in the art to be useful in formulating pharmaceutical compositions. Typically, for a successful therapy, the composition comprising the vector is prepared and then delivered as a vaccine, most typically via intramuscular injection. In one embodiment, the pharmaceutically acceptable vehicle may be a solid, and the composition may be in the form of a powder or tablet. A solid pharmaceutically acceptable vehicle may include one or more substances which may also act as flavouring agents, lubricants, solubilisers, suspending agents, dyes, fillers, glidants, compression aids, inert binders, sweeteners, preservatives, dyes, coatings, or tablet-disintegrating agents. The vehicle may also be an encapsulating material. In powders, the vehicle is a finely divided solid that is in admixture with the finely divided active agents according to the invention. In tablets, the active agent (e.g., recombinant vector according to the invention) may be mixed with a vehicle having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets may contain up to 99% of the active agents. Suitable solid vehicles include, for example calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins. In another embodiment, the pharmaceutical vehicle may be a gel and the composition may be in the form of a cream or the like. The pharmaceutical vehicle may be a liquid, and the pharmaceutical composition is in the form of a solution. Liquid vehicles are used in preparing solutions, suspensions, emulsions, syrups, elixirs and pressurised compositions. The active agent according to the invention may be dissolved or suspended in a pharmaceutically acceptable liquid vehicle such as water, an organic solvent, a mixture of both or pharmaceutically acceptable oils or fats. The liquid vehicle can contain other suitable pharmaceutical additives such as solubilisers, emulsifiers, buffers, preservatives, sweeteners, flavouring agents, suspending agents, thickening agents, colours, viscosity regulators, stabilisers or osmo-regulators. Suitable examples of liquid vehicles for oral and parenteral administration include water (partially containing additives as above, e.g., cellulose derivatives, typically sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols, e.g., glycols) and their derivatives, and oils (e.g., fractionated coconut oil and arachis oil). For parenteral administration, the vehicle can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid vehicles are useful in sterile liquid form compositions for parenteral administration. The liquid vehicle for pressurised compositions can be a halogenated hydrocarbon or other pharmaceutically acceptable propellant. Liquid pharmaceutical compositions, which are sterile solutions or suspensions, can be utilised by, for example, subcutaneous, intrathecal, epidural, intraperitoneal, intravenous, and particularly intramuscular injection. The agent may be prepared as a sterile solid composition that may be dissolved or suspended at the time of administration using sterile water, saline, or other appropriate sterile injectable medium. During the production of the vector according to the invention, the inventors used STING KO TetR cells. These cells are BHK21 cells, so permissive for MVA replication, but are engineered to lack the STING gene (BHK21 STING KO). Hence, these cells are unable to sense the excess of 2’3’-cGAMP produced by an MVA armed with cGAS. The inventors further modified these BHK21 STING KO cells to express the repressor of the promoter of the E. coli tetracycline operon (BHK21 STING KO TetR), with the view that constitutive expression of TetR would suppress, or limit, expression of cGAS from the saMVA and saMVA-CI, because in these viruses, the transgene, i.e., cGAS and cGAS-CI, respectively, is under the control of a viral promoter and the tetracycline regulatory element. Such BHK21 STING KO TetR cells remain unpublished. Accordingly, in a tenth aspect, there is provided a STING knockout cell line expressing a tetracycline repressor (TetR). In an eleventh aspect, there is provided use of the STING knockout cell line according to the tenth aspect for producing the vector according to the first aspect. In a twelfth aspect, there is provided a method of producing the vector according to the first aspect, the method comprising culturing the STING knockout cell line according to the tenth aspect, to thereby produce the vector of the first aspect. The use or method may be in vitro or in vivo. In one embodiment, the STING knockout cell line may be an animal STING knockout cell line. In one embodiment, the STING knockout cell line may be an avian STING knockout cell line. In one embodiment, the STING knockout cell line may be a mammalian STING knockout cell line. In one embodiment, the STING knockout cell line may be a BHK21 STING knockout cell line, a HeLa STING knockout cell line, a CHO STING knockout cell line, a HEK STING knockout cell line, a DF-1 STING knockout cell line, a LMH STING knockout cell line, or an immortalised fibroblast STING knockout cell line. Typically, however, the STING knockout cell line is a BHK21 STING knockout cell line. In one embodiment, the cell line contains at least one selectable marker. It will be appreciated that the at least one selectable marker may directly and / or indirectly allow permanent modification of the genetic content of the cell line. In one embodiment, the cell line may contain an antibiotic resistance gene and / or an antibiotic repressor gene. Typically, the cell line contains a puromycin resistance gene. In one embodiment, the cell line may comprise a cytosolic-replicating DNA viral genome, optionally wherein the viral genome replicates in the cytosol of the cell and assembles into a viral particle. The cytosolic-replicating DNA viral genome may be defined as under the first aspect. The method for producing the vector according to the first aspect may comprise growing at least one BHK21 STING KO TetR cell in cell culture vessels. The method may comprise infecting at least one BHK21 STING KO TetR cell with MVAΔF13 and subsequently transfecting the at least one cell with a transfer vector comprising human cGAS. The method may comprise incubating at least one BHK21 STING KO TetR cell until cytophatic effect (CPE) is observed and cell lysates are produced. The method may comprise recovering virus particles from the cell lysates. The method may comprise culturing progeny virus in at least one BHK21 STING KO TetR cell. The method may comprise identifying and selecting at least one individual focus of infection. It will be appreciated that a cytophatic effect (CPE) can refer to structural changes in host cells that are caused by viral invasion, and can thus indicate productive virus replication. The infecting virus causes lysis of the host cell or when the cell dies without lysis due to an inability to replicate. If a virus causes these morphological changes in the host cell, it is said to be cytopathogenic. Common examples of CPE include rounding of the infected cell, fusion with adjacent cells to form syncytia, and the appearance of nuclear or cytoplasmic inclusion bodies. In one embodiment, therefore, the cytophatic effect (CPE) may comprise cell rounding, cell swelling or shrinkage, detachment from the substrate, syncytia formation, inclusion bodies, granularity or vacuolisation, chromatin condensation or fragmentation, loss of contact inhibition, cell lysis, or apoptotic bodies. In one embodiment, the cytophatic effect (CPE) may be identified or observed by the use of light microscopy, fluorescence microscopy, histological staining, immunocytochemistry, transmission electron microscopy, scanning electron microscopy, flow cytometry, DNA laddering, plaque assay, and / or live-cell imaging. Typically, the method for producing the vector according to the first aspect comprises: (i) growing at least one BHK21 STING KO TetR cell in cell culture vessels; (ii) infecting the at least one BHK21 STING KO TetR cell with MVAΔF13 and subsequently transfecting the at least one cell with a transfer vector comprising human cGAS; (iii) incubating the at least one BHK21 STING KO TetR cell until cytophatic effect (CPE) is observed and cell lysates are produced; (iv) recovering virus particles from the cell lysates; (v) culturing progeny virus in at least one BHK21 STING KO TetR cell; and (vi) identifying and selecting at least one individual focus of infection. It will be appreciated that the invention extends to any nucleic acid or peptide or variant, derivative or analogue thereof, which comprises substantially the amino acid or nucleic acid sequences of any of the sequences referred to herein, including variants or fragments thereof. The terms “substantially the amino acid / nucleotide / peptide sequence”, “variant”, and “fragment”, can be a sequence that has at least 40% sequence identity with the amino acid / nucleotide / peptide sequences of any one of the sequences referred to herein, for example 40% identity with the sequences identified herein, and so on. Amino acid / polynucleotide / polypeptide sequences with a sequence identity which is greater than 40%, more typically greater than 50%, more typically greater than 55%, more typically greater than 65%, more typically greater than 70%, even more typically greater than 75%, and still more typically greater than 80% sequence identity to any of the sequences referred to are also envisaged. Typically, the amino acid / polynucleotide / polypeptide sequence has at least 85% identity with any of the sequences referred to, more typically at least 90% identity, even more typically at least 92% identity, even more typically at least 95% identity, even more typically at least 97% identity, even more typically at least 98% identity and, most typically at least 99% identity with any of the sequences referred to herein. The skilled technician will appreciate how to calculate the percentage identity between two amino acid / polynucleotide / polypeptide sequences. In order to calculate the percentage identity between two amino acid / polynucleotide / polypeptide sequences, an alignment of the two sequences must first be prepared, followed by calculation of the sequence identity value. The percentage identity for two sequences may take different values depending on:- (i) the method used to align the sequences, for example, ClustalW, BLAST, FASTA, Smith-Waterman (implemented in different programs), or structural alignment from 3D comparison; and (ii) the parameters used by the alignment method, for example, local vs global alignment, the pair-score matrix used (e.g., BLOSUM62, PAM250, Gonnet etc.), and gap-penalty, e.g., functional form and constants. Having made the alignment, there are many different ways of calculating percentage identity between the two sequences. For example, one may divide the number of identities by: (i) the length of shortest sequence; (ii) the length of alignment; (iii) the mean length of sequence; (iv) the number of non-gap positions; or (v) the number of equivalenced positions excluding overhangs. Furthermore, it will be appreciated that percentage identity is also strongly length dependent. Therefore, the shorter a pair of sequences is, the higher the sequence identity one may expect to occur by chance. Hence, it will be appreciated that the accurate alignment of protein or DNA sequences is a complex process. The popular multiple alignment program ClustalW (Thompson et al., 1994, Nucleic Acids Research, 22, 4673-4680; Thompson et al., 1997, Nucleic Acids Research, 24, 4876-4882) is one way for generating multiple alignments of proteins or DNA in accordance with the invention. Suitable parameters for ClustalW may be as follows: For DNA alignments: Gap Open Penalty = 15.0, Gap Extension Penalty = 6.66, and Matrix = Identity. For protein alignments: Gap Open Penalty = 10.0, Gap Extension Penalty = 0.2, and Matrix = Gonnet. For DNA and Protein alignments: ENDGAP = -1, and GAPDIST = 4. Those skilled in the art will be aware that it may be necessary to vary these and other parameters for optimal sequence alignment. Typically, calculation of percentage identities between two amino acid / polynucleotide / polypeptide sequences may then be calculated from such an alignment as (N / T)*100, where N is the number of positions at which the sequences share an identical residue, and T is the total number of positions compared including gaps and either including or excluding overhangs. Typically, overhangs are included in the calculation. Hence, a most typical method for calculating percentage identity between two sequences comprises (i) preparing a sequence alignment using the ClustalW program using a suitable set of parameters, for example, as set out above; and (ii) inserting the values of N and T into the following formula:- Sequence Identity = (N / T)*100. Alternative methods for identifying similar sequences will be known to those skilled in the art. For example, a substantially similar nucleotide sequence will be encoded by a sequence which hybridises to DNA sequences or their complements under stringent conditions. By stringent conditions, the inventors mean the nucleotide hybridises to filter-bound DNA or RNA in 3x sodium chloride / sodium citrate (SSC) at approximately 45ºC followed by at least one wash in 0.2x SSC / 0.1% SDS at approximately 20-65ºC. Alternatively, a substantially similar polypeptide may differ by at least 1, but less than 5, 10, 20, 50 or 100 amino acids from the sequences shown herein. Due to the degeneracy of the genetic code, it is clear that any nucleic acid sequence described herein could be varied or changed without substantially affecting the sequence of the protein encoded thereby, to provide a functional variant thereof. Suitable nucleotide variants are those having a sequence altered by the substitution of different codons that encode the same amino acid within the sequence, thus producing a silent (synonymous) change. Other suitable variants are those having homologous nucleotide sequences but comprising all, or portions of, sequence, which are altered by the substitution of different codons that encode an amino acid with a side chain of similar biophysical properties to the amino acid it substitutes, to produce a conservative change. For example, small non-polar, hydrophobic amino acids include glycine, alanine, leucine, isoleucine, valine, proline, and methionine. Large non-polar, hydrophobic amino acids include phenylalanine, tryptophan and tyrosine. The polar neutral amino acids include serine, threonine, cysteine, asparagine and glutamine. The positively charged (basic) amino acids include lysine, arginine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid. It will therefore be appreciated which amino acids may be replaced with an amino acid having similar biophysical properties, and the skilled technician will know the nucleotide sequences encoding these amino acids. All of the features described herein (including any accompanying claims, abstracts and drawings), and / or all of the steps of any method or process so disclosed, may be combined with any of the above aspects in any combination, except combinations where at least some features and / or steps are mutually exclusive. For a better understanding of the invention, and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example, to the accompanying Figures, in which:- Figure 1 shows an embodiment of the saMVA WT, saMVA CI and FMVA-Ctrl vector design. The vector design consists of flanking regions of 250 bp of homology to the MVA genome on either side of the F13L locus. From 5’ to 3’, the internal components of the transfer vector include the F13L gene, including promoter and terminator sequences, the p7.5 promoter, two copies of the Tet Operator sequence (TetO), a copy of human cGAS, codon optimised for poxviral expression. For saMVA CI, the catalytic site of cGAS is inactivated, and for FMVA-Ctrl, this ORF is not present. The vector then includes the GFP promoter, followed by GFP edited at the nucleotide level to reduce the risk of recombination to the pUC13 vector. Figure 2 shows the generation of “self-adjuvanting” Modified vaccinia Ankara (saMVA) wildtype (WT), saMVA catalytically inactive (CI), i.e., comprising a catalytically inactive copy of cGAS, and FMVA-Ctrl (carrying an empty locus). A) Schematic of the workflow for generation of saMVA WT, saMVA CI and FMVA-Ctrl using the F13L selection process. B) BHK21 STINGKO TetR cells were infected with candidate viruses and 48 h post- infection cells were proteinase K treated and used as template for PCR using primers sitting in F13L and GFP. The PCR product was run on a 1% agarose gel and visualised. V represents the band obtained from amplifying viral DNA and P represents the band obtained from amplifying donor plasmid DNA. Figure 3 shows that saMVA WT and saMVA CI induce cGAS expression in target cells. THP-1 cells were infected with the indicated virus at 5 PFU / cell and samples harvested at 8 hours post-infection in RIPA buffer. Samples were assessed for expression of Tubulin, Flag (cGAS) and C6 (viral protein, marker of infection) by immunoblotting. Figure 4 shows that saMVA WT and saMVA CI induce stronger innate immune activation in monocyte-derived macrophages than control MVA (FMVA-Ctrl). PMA-differentiated monocytes carrying a luciferase reporter under the control of the promoter of the immune gene IFIT1 were used to monitor innate immune activation upon infection with the indicated virus at the indicated multiplicity of infection (MOI, PFU / cell) and at 24 hours post-infection the supernatant was assessed for luciferase activity. Figure 5 shows that saMVA WT and saMVA CI induce greater phosphorylation of STING and IRF3 than FMVA-Ctrl. THP-1 IFIT1-GLuc macrophages were infected with the indicated virus at 5 PFU / cell and samples harvested at 8 hours post-infection in RIPA buffer. Samples were assessed for phosphorylated STING and IRF3 as well as total STING, total IRF3, Flag (cGAS), Tubulin and B14 (as a marker of viral infection). Figure 6 shows that saMVA WT induces stronger dimerisation of STING, which is a hallmark of STING activation, than FMVA-Ctrl. A strong band at 75 kDa, which represents the STING dimer, and a weak band at 35 kDa, which represents the STING monomer, can be seen for saMVA WT. In contrast, a weak band at 75 kDa and a strong band at 35 kDa can be seen for FMVA-Ctrl. Figure 7 shows that saMVA remains active in THP-1-IFIT1-Gluc cells lacking cGAS, demonstrating that the expression of cGAS by saMVA can induce immune activation, even if cells are deficient for cGAS. THP-1 IFIT-GLuc macrophages lacking cGAS were infected with saMVA WT, saMVA CI, or FMVA-Ctrl at the indicated multiplicity of infection (MOI, PFU / cell) and at 24 hours post-infection the supernatant was assessed for luciferase activity. A) IFIT-Gluc fold induction relative to mock was statistically significantly greater over both saMVA Cl and MVA-Ctrl in THP-1-IFIT1-Gluc cells lacking cGAS. B) A strong band at 35 kDa, which represents pSTING, can be seen for saMVA WT in both THP-1 Dual control cells, as well as those THP-1 Dual cells lacking cGAS. Figure 8 shows that saMVA WT induces higher production of type I and type III interferon than FMVA-Ctrl. THP-1 IFIT-GLuc macrophages were infected with saMVA WT or FMVA-Ctrl for 2, 4, or 6 hours prior to harvesting total RNA which was used to generate cDNA and assessed for expression of IFNB1 and IFNL1 relative to 18S RNA. Figure 9 shows that saMVA WT induces higher production of 2’3’-cGAMP than FMVA-Ctrl during infection. THP-1 IFIT-GLuc macrophages were infected with saMVA WT or FMVA- Ctrl at 5 PFU / cell for 8 hours then supernatant and cells were harvested and assessed for concentration of 2’3’-cGAMP. ^ indicates below limit of accurate quantification but above limit of detection. Figure 10 shows that saMVA WT induces signalling in bystander cells via transport of 2’3’-cGAMP. A) A co-culture experiment was set up using HEK293T (naturally deficient for cGAS and STING). HEK293T cells (stimulator cells) were infected with saMVA WT at 2 PFU / cell for 2 h or left uninfected. HEK293T cells, transfected with an IFNB1-firefly luciferase (FLuc) reporter and a TK-Renilla luciferase (RLuc) reporter (reporter cells) were reconstituted with STING, or an empty vector, to enable recognition of cGAMP and B2 (an enzyme that degrades cGAMP) to demonstrate specificity for cGAMP. Cells were transfected for 4 h and then co-cultured with stimulator cells for 24 h. IFNB1-GLuc reporter data is presented as a ratio to TK-FLuc over uninfected cells. Signal is only observed in STING-reconstituted reporter cells co-cultured with infected stimulator cells, and this abrogated when reporter cells expressed a cGAMP nuclease. B) A cartoon which illustrates the process by which saMVA WT induces signalling in bystander cells via transport of 2’3’-cGAMP. Figure 11 shows a Volcano Plot of significantly differentially expressed genes (log 2 fold change >0) comparing saMVA WT infected human primary monocyte-derived macrophages (MDMs) to FMVA-Ctrl infected MDMs. Figure 12 shows KEGG pathway analysis of differentially enriched genes comparing saMVA WT infected MDMs to FMVA-Ctrl infected MDMs. Pathways relevant to innate immune signalling are highlighted in red. Figure 13 shows that saMVA WT induces significantly higher production of cytokines than FMVA-Ctrl. A) Heatmap of significantly differentially expressed individual genes induced by saMVA WT or FMVA-Ctrl infection relative to uninfected cells (mock)in MDM. B) As A but comparing saMVA WT infected cells to FMVA-Ctrl infected cells. C) FPKM of selected genes from saMVA WT and FMVA-Ctrl samples. D) RNA-sequencing data was analysed by performing qPCR on the same RNA assessing upregulation of IFNB1, CXCL10, and IFIT1 relative to 18S RNA. E) As in D but assessing C6L relative to 18S RNA. Data in all graphs are presented as the means ± the SD, each performed in triplicate. *, P < 0.005; **, P < 0.01 (unpaired Student t test). Figure 14 shows that saMVA WT and saMVA CI induce a greater T cell response than FMVA-Ctrl. Average percentage of IFN-γ+, CD8+ T cells present in splenocytes isolated from vaccinated C57BL / 6 mice and stimulated for 16 hours with 1 μg / mL poxviral peptide cocktail. Experimentation with animals was performed under UK project license PP2250582. Figure 15 shows that a tetracycline repressor (TetR) limits the expression of transgenes whose promoter had the TetO in BHK21-STING-KO cells. Clone 8 shows that, in the presence of doxycycline (a tetracycline-binding protein), the expression of FLAG-B2 is rescued relative to the lane where doxycycline is absent, and therefore also shows the TetO is repressed by tetracycline. Figure 16 shows the skeletal structure of 2’3’-cGAMP. Figure 17 shows that saMVA (saMVA WT) induces a stronger cellular immune response (T cell response) than MVA. Data for CD8+ T cells (positive for either CD107 or TNFα) present in splenocytes isolated from vaccinated C57BL / 6 mice and stimulated for 16 hours with 1 μg / mL a poxviral peptide, namely either B8R peptide, E9L peptide, L4R peptide, or A19L peptide. Experimentation with animals was performed under UK project license PP2250582. Figure 18 shows that saMVA (saMVA WT) induces a cellular immune response (T cell response). Data for CD8+ T cells (positive for either IFN-γ and CD107 or TNFα) present in splenocytes isolated from vaccinated C57BL / 6 mice and stimulated for 16 hours with 1 μg / mL a poxviral peptide, namely either B8R peptide, E9L peptide, L4R peptide, or A19L peptide. Experimentation with animals was performed under UK project license PP2250582. Figure 19 shows immune gene expression of IFN-β, CXCL10, and ISG15 upon delivery of MVA, saMVA, and derivatives thereof (namely R255E and NN153 / 154AA) onto human foreskin fibroblasts (multiplicity of infection of 5, 16 h post infection). Data are presented as fold increase over mock-treated cells. Examples In order to enhance the immunogenicity of MVA, the inventors have generated a MVA- based vaccine vector which encodes a functional copy of the mammalian pattern recognition receptor (PRR) cyclic GTP-ATP synthase (cGAS), which, as discussed, detects double stranded DNA (dsDNA) in the cytoplasm and induces antiviral signalling (12) via production of the secondary messenger 2’3’-cyclic GMP-AMP (2’3’-cGAMP) (13). The inventors have surprisingly discovered that the delivery of a cyclic di-nucleotide synthetase enzyme gene to target cells in a cytosolic-replicating vaccine vector is a viable strategy for enhancing the induction of innate immune signalling. As such, the inventors’ discovery offers a platform to enhance the immune activation and immunogenicity of vaccines and therapeutic vectors. Accordingly, the inventors have surprisingly discovered a novel strategy to solve the problems associated with the limited immunogenicity of the cytosolic-replicating DNA virus, MVA. The inventors have shown that, by arming a vaccine vector with its host sensor, for example, cGAS, all cells at the site of vaccination, and hence antigen production, are provided the ability to sense the vector DNA genome, thus enhancing the production of the highly immunogenic second messenger 2'3'-cGAMP, which is a natural compound with well-known adjuvanting properties, and eventually soluble immune mediators, including interferons (IFNs). Materials and Methods Cell Culture and Viruses BHK21 and HEK293T cells were passaged in Dulbecco’s Modified Eagle Medium (DMEM, Sigma) supplemented with 10% (v / v) foetal bovine serum (FBS, BioWest), 100 U / mL penicillin, and 100 µg / mL streptomycin (Life Technologies). THP-1 IFIT1-GLuc (14) cells were passaged in Roswell Park Memorial Institute Medium (RPMI, Gibco) supplemented with 10% (v / v) FBS, 100 U / mL penicillin, and 100 µg / mL streptomycin. MVAΔF13 (15) were obtained from Rafael Blasco (Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (I.N.I.A.), Madrid, Spain). saMVA WT, saMVA CI (carrying a catalytically inactive copy of cGAS), and FMVA-Ctrl (carrying an empty locus) were grown in a BHK21 STING KO TetR cell line (ref.16, see first paragraph of results), and titrated by counting fluorescent foci. Generation of saMVA WT, saMVA CI and FMVA-Ctrl A T25 of BHK21 STINGKO TetR cells at 80% confluency were infected with MVAΔF13 at 2 PFU / cell for 90 minutes, with the flask being rocked every 30 minutes to ensure even distribution of viral particles. During the 90 minute incubation, transfection complexes were prepared for the appropriate pUC13 -ecoGPT-GFP based saMVA transfer vector plasmid. Viral inoculum was removed and replaced with DMEM, supplemented with 2% (v / v) FBS, prior to adding the transfection complexes and rocking the flask to ensure even distribution. After cytopathic effect (CPE) was observed, the cells were harvested by scraping and freeze thawed 3 times, and small volumes were used to infect confluent 6-well plates of BHK21 STING KO TetR in liquid culture to allow outgrowth of the recombinant viruses expressing F13. After CPE was observed, the cells were harvested and used for plaque purification, where dilutions of these enriched stocks were used to infect 6-well plates of BHK21 STING KO TetR cells for 60-90 minutes at 37°C prior to removing inoculum and adding 2 mL of 1% (w / v) agarose overlay. The infection was monitored, and foci of cells fluorescing green with cell-to-cell spread capacity were picked and taken forward. This was repeated until 3 rounds had passed since the cell-to- cell spread incompetent red fluorescent parental virus had not been observed for 3 rounds of purification. These foci were then used to generate viral stocks. PCR to verify virus identity BHK21 STINGKO TetR cells were infected with candidate virus for 48 hours in liquid culture. The cells were detached from the plate in their media, and an aliquot of this was treated with proteinase K (QIAgen) for 15 minutes at 50°C and then inactivated for 10 minutes at 70°C. This was used as template for PCR using the GoTaq (Promega) system according to manufacturer’s instructions using saMVA-F (5’-AGGTACCGGTGCAAATGG-3’) (SEQ ID No: 14), and saMVA R (5’-TAAACTTGTGGCCGTTCACG-3’) (SEQ ID No: 15), primers. SDS-PAGE and Immunoblotting Cells were harvested by lysis in radioimmunoprecipitation assay (RIPA) buffer (50 mM Tris / HCl, 150 mM NaCl, 1% (v / v) NP40, 0.5% (w / v) sodium deoxycholate, 0.1% (v / v) SDS), which was supplemented with protease and phosphatase inhibitors (Roche) as required. Lysed cells were agitated for 20 minutes at 4°C prior to centrifugation at 17000 g for 15 minutes. The supernatant was transferred to a tube and supplemented with SDS loading buffer, and boiled for 5 minutes at 95°C. These were then run on a 12% (v / v) SDS-PAGE gel and transferred to a nitrocellulose membrane (GE Healthcare) using a semidry Trans-blot transfer unit (Bio-Rad). After transfer, the membranes were blocked for 30 minutes in 5% (w / v) milk (Sigma) dissolved in PBS; this was replaced with 5% (w / v) milk dissolved in PBS supplemented with 0.1% (v / v) Tween20 and primary antibodies including α-Tubulin (Millipore, 1:5000), α-Flag (Sigma, 1:5000), α- pIRF3 (Abcam, 1:2000), α-IRF3 (Abcam, 1:2000), α-pSTING (Cell Signalling Technology, 1:1000), α-STING (Cell Signalling Technology, 1:1000), or antisera for VACV proteins. which were received from Professor Geoff Smith (University of Oxford, Oxford, United Kingdom): α-C6 (1:500) and α-B14 (1:500). The primary antibodies were detected with secondary antibodies conjugated to IRDye (LI-COR Biosciences) and visualised using the Odyssey CLx infrared imager (LI-COR Biosciences). THP-1 Luciferase Assay THP-1 IFIT1-GLuc cells were differentiated for 48 hours in the presence of 50 ng / mL PMA. After this, the cells were infected in triplicate with the indicated virus at the indicated PFU / cell for 24 hours. The luciferase activity was then assessed with a Clariostar plate reader (BMG Biotech) using coelenterazine (NanoLight Technology) at 2 μg / mL. Quantitative PCR (qPCR) THP-1 IFIT1 Gluc cells were differentiated for 48 hours in the presence of 50 ng / mL PMA. The cells were infected with 5 PFU / cell of the indicated virus on ice for 90 minutes to synchronise infection. At the indicated time point, cells were washed once with PBS and total RNA harvested according to manufacturer’s instructions using the RNeasy kit (QIAgen) and treated with a Rnase-free Dnase I kit (Invitrogen), and used as template to synthesise cDNA using the Superscript III kit (Inivtrogen) to manufacturer’s instructions. cDNA was diluted 1:5 in nuclease-free water and used as template to perform qPCR with SYBR green reagents (Applied Biosystems) using a QuantStudio 5 (Thermo Fisher) instrument. Expression levels of IFNB1 (forward 5’- ACATCCCTGAGGAGATTAAGCA-3’ (SEQ ID No: 16); reverse 5’- GCCAGGAGGTTCTCAACAATAG-3’ (SEQ ID No: 17)), and IFNL1 (forward 5’- ACATTGGCAGGTTCAAATCTC-3’ (SEQ ID No: 18); reverse 5’-TGAGTGACTCTTCCAAGGC- 3’ (SEQ ID No: 19)) were normalised first to 18S RNA expression (forward 5’- GTAACCCGTTGAACCCCA-3’ (SEQ ID No: 20); reverse 5’-CCATCCAATCGGTAGTAGCG-3’ (SEQ ID No: 21)), and then the unstimulated mock to calculate the fold-upregulation. To validate the transcriptomic data from primary human macrophages CXCL10 (forward 5’- TGGCATTCAAGGAGTACCTC-3’ (SEQ ID No: 22); reverse 5’- TTGTAGCAATGATCTCAACACG-3’ (SEQ ID No: 23)), IFIT1 (forward 5’- CCTGAAAGGCCAGAATGAGG-3’ (SEQ ID No: 24); reverse 5’- TCCACCTTGTCCAGGTAAGT- 3’ (SEQ ID No: 25)), and C6L (forward 5’- GATTATTCCGGCAGCGAACTTG-3’ (SEQ ID No: 26); reverse 5’- GACGCGGTTAGATATTACGATGGT-3’ (SEQ ID No: 27)) primers were also used. 2’3’-cGAMP ELISA THP-1 IFIT1 GLuc cells were differentiated for 48 hours in the presence of 50 ng / mL PMA. The cells were infected with 5 PFU / cell of the indicated virus for 8 hours. At this time point, the supernatant was collected, and the cells lysed with M-PER Mammalian Protein Extraction Reagent (Thermo Scientific). Both supernatant and lysate were immediately run using a cGAMP ELISA kit (Cayman Chemical), and data analysed according to manufacturer’s instructions. HEK293T co-culture reporter HEK293T cells were seeded into 96-well and 6-well plates. The 96-well plate was transfected with IFNB1-FLuc and TK-GLuc plasmids and either empty vector, STING, or STING and VACV B2 to act as the reporter cells and left for 4 hours at 37°C. The 6-well plates were either infected with saMVA WT at 2 PFU / cell or mock infected to act as stimulator cells and incubated at 37°C for 2 hours to allow viral entry. At this point, the stimulator cells were trypsinised to detach from the plates, neutralised, and the cell suspension counted using Trypan Blue (Gibco); spare wells from the reporter cell plate were also trypsinised, neutralised, and counted. The stimulator cells were then seeded into the reporter cell plates at a ratio of 1 : 0.25 reporter : stimulator.24 hours post-co- culture, the cells were lysed with passive lysis buffer (Promgega) and assessed for luminescence with a Clariostar plate reader (BMG Biotech). Transcriptomic analysis Primary human monocyte-derived macrophages were infected with either saMVA WT or FMVA-Ctrl at 5 PFU / cell for 8 hours. RNA was purified as described above using the RNeasy mini RNA extraction kit with on-column DNase treatment, and sent for bulk RNA sequencing by Novogene. Messenger RNA was purified from total RNA using poly-T oligo- attached magnetic beads. After fragmentation, the first strand cDNA was synthesised using random hexamer primers, followed by the second strand cDNA synthesis using either dUTP for directional library or dTTP for non-directional library. The library was checked with Qubit and real-time PCR for quantification and bioanalyzer for size distribution detection. Quantified libraries were then pooled and sequenced on an Illumina platform. RNA-seq reads were aligned to the Homo Sapiens genome using HISAT2 (33), and featureCounts (34) v1.5.0-p3 was used to count the read numbers mapped to each gene, and the FPKM of each gene was calculated based on the length of the gene and reads count mapped to it. Differentially expressed genes (DEG) were calculated using DESeq2 (35). The resulting P-values from DESeq2 were adjusted using the Benjamini and Hochberg's approach for controlling the false discovery rate. Genes with an adjusted P-value <0.05 found by DESeq2 were assigned as differentially expressed. DEGs were then used for KEGG pathway enrichment analysis (36). Pathway p-values <0.05 were considered significant. Heat maps were generated using GraphPad Prism (version 10) and KEGG pathway analysis figures were generated using SRPlot. Mice studies Female C57BL / 6 mice of at least 6 weeks of age were obtained from Charles River; all maintenance and experimentation upon animals was performed in agreement with the ethical requirements of EU legislation under PROEX 025 / 16 (Mouse models of viral pathogenesis, PI A Alcami). Intracellular cytokine staining of splenocytes: 7 days post- vaccination mice were sacrificed, and the spleen of each animal was extracted and maintained in RPMI supplemented with 2% (v / v) FBS, 10 μM HEPES, and 2 mM EDTA. The spleens were disintegrated by passing the spleen through a 100 μM filter cell strainer (Falcon) until a cell suspension was created. Cells were centrifuged for 5 minutes at 1500 rpm and resuspended in 1 mL of erythrocyte lysis buffer (150 mM NH4Cl, 10 mM K¬HCO¬3, 100 μM EDTA), and erythrocytes were allowed to lyse for 5 minutes at RT. This was neutralised with RPMI supplemented with 2% (v / v) FBS, 10 μM HEPES, and 2 mM EDTA and subsequently centrifuged for 5 minutes at 1500 rpm. Splenocytes were cultured in RPMI supplemented with 10% (v / v) FBS, 3 μg / mL brefeldin A (BFA), 2 μM moenisin, and 1 : 100 α-CD107a-FITC antibody (BD Biosciences). One replicate of splenocytes was also supplemented with 1 μg / mL PepMix Pan-Poxviridae Select peptide cocktail (JPT). The cells were cultured for 16 hours, and then transferred to a v-bottom 96-well plate for staining performed on ice and in the dark. Prior to fixing, each centrifugation was performed for 3 minutes at 1500 rpm. Cells were pelleted and washed with PBS. The cells were then resuspended in PBS supplemented with 1 : 1000 Ghost Dye 780 live / dead stain (Cytek) for 20 minutes; this was neutralised with PBS supplemented with 2% (v / v) FBS and centrifuged. The cells were then resuspended in PBS supplemented with 1 : 50 Fc block (BD Biosciences) and incubated for 15 minutes. Cell surface markers were stained by adding PBS supplemented with 2% (v / v) FBS containing a final dilution of 1 : 100 α-CD3-PerCP, α-CD4-BV605, and α-CD8-PE (BD Biosciences) to each well for a further 20 minutes. This was neutralised with PBS supplemented with 2% (v / v) FBS and centrifuged. Cells were resuspended in Cytofix / cytoperm reagent (BD Bioscience) for 20 minutes. After fixing, the cells were centrifuged for 5 minutes at 2000 rpm and washed with Perm / wash solution (BD Bioscience). The plate was centrifuged and resuspended with Perm / wash solution supplemented with 1 : 50 Fc Block for 15 minutes. To stain for intracellular cytokines, perm / wash solution supplemented with a final dilution of 1 : 100 α-IFN-γ-BV421, α-IL-2- APC, and α-TNFα-PE-Cy7 (BD Biosciences) was added to the cells and incubated for a further 20 minutes. This was neutralised with Perm / wash solution and centrifuged. The cells were washed with Perm / wash solution and centrifuged. The cells were subsequently resuspended in PBS and analysed using a BD FACSCanto flow cytometer. Example 1 - Generation of saMVA WT, saMVA CI, and FMVA-Ctrl To generate the above viruses, namely saMVA WT, saMVA CI, and FMVA-Ctrl, BHK21 STING KO TetR cells were used. These cells are BHK21 cells, so permissive for MVA replication, but were engineered to lack the STING gene (BHK21 STING KO). Hence, these cells are unable to sense the excess of 2’3’-cGAMP produced by an MVA armed with cGAS. These cells were published in Hood et al., (2022) (16). BHK21 STING KO cells were further modified to express the repressor of the promoter of the E. coli tetracycline operon (BHK21 STING KO TetR), with the view that constitutive expression of TetR would suppress, or limit, expression of cGAS from the saMVA and saMVA-CI, because in these viruses, the transgene, i.e., cGAS and cGAS-CI, respectively, is under the control of a viral promoter and the tetracycline regulatory element. BHK21 STING KO TetR cells remain unpublished. Referring to Figure 2A, saMVA WT and the control viruses were generated by infecting BHK21 STING KO TetR cells with MVAΔF13 at 5 PFU / cell prior to transfecting the cells with pUC13 plasmid encoding the appropriate transfer vector. At the point of significant cytopathic effect (CPE) being observed, the progeny virus was harvested. This mixture of viral progeny was enriched for F13L positive viruses by infecting the wells of a 6-well plate of BHK21 STING KO TetR cells in liquid culture to allow the outgrowth of the fitter virus. When CPE was observed, the wells were harvested and spun down as before. These enriched viral populations were then each used to infect BHK21 STINGKO TetR cells at increasing dilution factors, and 1 hour after infection covered with 1% low-gelling agarose overlay. Around 48 – 72 hours after infection, cells were assessed for fluorescence, and large GFP positive foci were picked through the agarose and used to infect further plates of BHK21 STING KO TetR cells. This was performed until no red fluorescent cells were observed, as this was contaminant parental virus, and for three rounds of purification after that. The purified green foci were then scaled up for further analysis, as shown in Figure 2A. In order to screen the purified viral foci for the integrity of the genetic insert, BHK21 STINGKO TetR cells were seeded into a 24-well plate and infected with 50 µL of the viral stock.48 hours after infection, the cells were harvested by scraping and freeze thawed 3 times to release viral particles from the cells. These particles were then treated with proteinase K for 15 minutes, then heat inactivated for 10 minutes to disrupt the viral particles so that the viral DNA could be used as PCR template. The PCR was performed using primers specific to the 3’ end of the F13L gene and the 5’ of the GFP gene to amplify the cGAS ORF, and products were subsequently run on an agarose gel. As both primers were not present in the parental virus, the presence of a PCR product implies the integration of the transfer vector. As shown in Figure 2B, all three viruses showed amplicons of the same size as the transfer vector, which were subsequently sent for sequencing to verify absence of undesired mutations. All three viruses were fully sequenced prior to further testing. Example 2- saMVA WT and saMVA CI induce cGAS expression in target cells After stocks of the recombinant MVA vectors were generated, the ability of these viruses to induce transgene expression in target cells was assessed by infecting THP-1 IFIT1- GLuc macrophages with 5 PFU / cell of each virus.8 hours post-infection, the samples were harvested and assessed for the expression of cGAS via its Flag-tag by immunoblotting, using tubulin and C6 as controls for total protein and levels of viral infection, respectively. As shown in Figure 3, cGAS was detected in the samples infected with saMVA WT and saMVA CI, indicating that the transgene was expressed as intended; these results were validated by equivalent levels of the loading control proteins. Example 3- saMVA WT and saMVA CI induce greater activation of IRF3 signalling compared to FMVA-Ctrl The ability of saMVA WT and saMVA CI to induce the activation of innate immunity was characterised relative to FMVA-Ctrl, which phenocopies standard MVA which is being used in the clinic. This was assessed by infecting THP-1 IFIT1-GLuc cells as monocytes with all three viruses at several PFU / cell. The activation of innate immunity was measured by assessing the production of Gaussia luciferase, which is under the control of the IRF3 dependent IFIT1 promoter, at 24 hours post-infection. As shown in Figure 4, it was observed that saMVA WT induced around 5-fold greater activation of the reporter than FMVA-Ctrl, while saMVA CI induced around 2.5-fold greater activation. This indicates that the cGAS expression induced in target cells by saMVA WT and saMVA CI is capable of significantly enhancing activation of innate immune signalling compared to conventional MVA. To validate these findings, the ability of the viruses to induce phosphorylation of STING and IRF3 during infection was assessed via immunoblotting; THP-1 IFIT1-GLuc cells were differentiated into macrophages and infected with saMVA WT, saMVA CI, and FMVA-Ctrl at 5 PFU / cell, and at 8 hours post-infection the samples were harvested. These samples were assessed for phosphorylated IRF3, phosphorylated STING, total IRF3, total STING, Flag, Tubulin, and B14. As shown in Figure 5, these results demonstrated a similar trend, with saMVA WT inducing the greatest phosphorylation of STING and IRF3, while saMVA CI had an intermediate phenotype between saMVA WT and FMVA-Ctrl. These findings indicate that the copy of cGAS encoded by saMVA WT is more able to induce downstream signalling than the catalytically inactive version encoded by saMVA CI, and both are more able to activate the cGAS / STING pathway than FMVA-Ctrl. Example 4 - saMVA WT induces greater transcription of type I and type III interferon than FMVA-Ctrl The production of type I interferon has been demonstrated to be key to bridging the activation of innate immunity and the adaptive immune response. In order to verify whether saMVA WT induces higher production of these key cytokines, THP-1 IFIT1-GLuc macrophages were infected with saMVA WT or FMVA-Ctrl at 5 PFU / cell and total RNA was harvested at 2, 4, and 6 hours post-infection. This was used as template for qPCR, and the upregulation of IFNB1 and IFNL1 was assessed relative to unstimulated cells. As shown in Figure 8, upregulation of IFNB1 transcription was significantly higher in response to saMVA WT at all the time points measured, and transcripts were detectable at 2 hours post-infection, which was not observed in response to FMVA-Ctrl, thus indicating that the kinetics and magnitude of the response had been increased. A similar trend was observed with transcription of IFNL1, although there was no detectable induction of transcription at 2 hours post-infection for this cytokine. Example 5 - saMVA WT induces higher production of 2’3’-cGAMP than FMVA-Ctrl during infection A key facet of the rationale of saMVA, is the increased capacity to generate 2’3’-cGAMP, which is capable of activating STING in bystander cells and inducing the production of cytokines to activate the adaptive immune response. To assess this, THP-1 IFIT1-GLuc macrophages were infected with either saMVA WT or FMVA-Ctrl at 5 PFU / cell for 8 hours; at this time point, the supernatant was taken and the cells lysed, and both were assessed for the concentration of 2’3’-cGAMP. As shown in Figure 9, it was observed that there was around 10-fold more 2’3’-cGAMP generated in cell lysates infected with FMVA- Ctrl than the mock, but there was a 100-fold increase in the concentration present in lysates from cells infected with saMVA WT. A similar trend was observed in the supernatant, indicating that infection with saMVA WT led to increased accumulation of 2’3’-cGAMP in the extracellular medium. Example 6 - saMVA WT induces signalling in bystander cells via transport of 2’3’-cGAMP In order to demonstrate the capacity of saMVA WT to induce signalling in bystander cells, a HEK293T co-culture assay was performed, adapted from Ablasser et al., (17). This assay leverages the fact that HEK293T cells are deficient for DNA sensing, but this can be recapitulated by ectopic expression of cGAS and STING. Two pools of HEK293T cells were generated and then combined; the first pool, here referred to as stimulator cells, were infected with either saMVA WT or mock infected to reconstitute the capacity to produce cGAMP, while the second pool, referred to as reporter cells, were co- transfected with STING, and a IFNB1-Luciferase reporter plasmid which could respond to 2’3’-cGAMP but not produce it. As shown in Figure 10, when combined, luciferase activity was only observed when saMVA WT infected cells were co-cultured with reporter cells transfected with STING, and this could be abrogated by co-transfecting the reporter cells with poxin from VACV, which is an enzyme capable of linearising 2’3’-cGAMP and rendering it incapable of activating STING. Together, these data indicate that saMVA WT is capable of inducing the activation of the IFNB1 promoter in bystander cell via the action of 2’3’-cGAMP transport. Example 7 - Transcriptomic analysis indicates significantly higher cytokine production in response to saMVA WT infection In order to assess the change in global transcription in response to infection with saMVA WT compared to infection with FMVA-Ctrl, primary human monocyte-derived macrophages (MDMs) were isolated and infected with either virus ex vivo at 5 PFU / cell for 8 hours. At this point, total RNA was isolated and sent for transcriptomic analysis. The induction of cGAS expression in target cells during infection led to differential expression (p < 0.05, >log2FC 0) of over 5000 transcripts, as shown in Figure 11. As shown in Figure 12, pathway enrichment analysis (KEGG) indicated that several of the most differentially expressed pathways were involved in innate immune signalling, notably JAK-STAT signalling, RIG-I like receptor signalling, and TNF signalling pathways, indicating that saMVA leads to differential activation of several important immune signalling pathways. In order to contextualise these findings, specific genes were selected from the list of significantly upregulated differentially expressed genes ( > log2FC 0 and P < 0.05), to see whether these were more upregulated by saMVA WT than FMVA-Ctrl in comparison to the mock cells. As shown in Figure 13A, this panel included type I, type II, and type III interferons, as well as several cytokines including TNF and CCL5; the panel also included a variety of interferon-stimulated genes (ISGs) including effector proteins and those involved in innate immune signalling. With the exception of CXCL10, every gene in this panel was upregulated to a higher degree by saMVA WT, as shown in Figure 13B. This indicates that saMVA WT may be able to induce a stronger immune response in vivo, as it produces a higher level of interferons and important cytokines. The full panel of ISGs, including most members of the IFIT family and some important innate immune signalling factors, had higher differential expression in the saMVA WT infected samples than FMVA-Ctrl, indicating that the IRF3 and JAK-STAT pathways are being fully activated in these cells. These data were further investigated by confirming the fragments per kilobase per million reads (FPKM) of individual genes measured in each sample of the biological triplicate, and ensuring that these were significantly upregulated, as shown in Figure 13C. To further validate this data, the RNA used for sequencing was assessed for upregulation of selected genes by targeted qPCR; saMVA WT infection led to significantly higher expression of IFNB1, while FMVA-Ctrl led to significantly higher transcription of CXCL10, while there was no significant difference in expression of IFIT1 as assessed by qPCR, as shown in Figure 13D. Finally, to validate that the samples had been infected with equivalent amounts of the two viruses, the transcription of a viral gene C6L was assessed by qPCR and when normalised to 18S RNA; in the samples, it was observed that there was no significant difference in infection and that the PFU / cell were well matched, as shown in Figure 13E. Example 8 - saMVA WT and saMVA CI induce an enhanced T cell response in vivo compared to FMVA-Ctrl In order to determine whether the enhanced activation of innate immunity demonstrated by saMVA in vitro would translate to an increased T cell response in vivo, 6 week old female C57BL / 6 mice were inoculated with 1 x 106 pfu of saMVA WT, saMVA CI, or FMVA-Ctrl, along with a mock group inoculated with PBS. At 7 days post-inoculation, mice were sacrificed, and their spleens harvested. Splenocytes were isolated and cultured in the presence of a cocktail of poxviral peptides to stimulate activation of poxviral-specific T cell response. The cocktail of poxviral peptides used was PepMix™ Pan-Poxviridae Select, a virus-specific pool of 127 peptides (defined HLA class I & II- restricted T-cell epitopes) from selected proteins of Vaccinia virus (VACV), Variola virus (VARV), and Mpox virus (MPXV).16 hours post-stimulation, the splenocytes were fixed, stained, and analysed by flow cytometry. As shown in Figure 14, the mice inoculated with FMVA-Ctrl had around 2% IFN-γ+ CD8+ T cells after 16 hours of stimulation, while saMVA WT induced up to 10% IFN-γ+ CD8+ T cells. It was observed that saMVA CI induced a more consistent response of around 6% IFN-γ+ CD8+ T cells, which was significantly more than that induced by FMVA-Ctrl. Other cytokines, such as IL-2 and TNFα, showed a similar pattern, indicating that saMVA is capable of inducing a greater T cell response than conventional MVA in vivo. Example 9 - saMVA WT induces an enhanced T cell response in vivo compared to FMVA- Ctrl The example described above was repeated, with the exceptions that the mice were inoculated with saMVA WT only, and the splenocytes were isolated and cultured in the presence of individual poxviral peptides, namely B8R peptide, E9L peptide, L4R peptide, or A19L peptide, to stimulate activation of poxviral-specific T cell response, rather than as a combined cocktail of 127 peptides. Splenocytes were cultured in RPMI supplemented with 10% (v / v) FBS, 3 ug / ml brefeldin A (BFA), and 2uM monensin, and supplemented with 1 ug / ml of the indicated poxvirus peptides (i.e., B8R peptide, E9L peptide, L4R peptide, or A19L peptide). To stain for intracellular cytokines, perm / wash solution supplemented with anti-IFN-γ, anti-CD107a and anti-TNFα (BD Biosciences) was added to the cells. Referring to Figure 17, it is shown that the number of poxvirus-specific CD8 T cells positive for positive for CD107 or TNFα increases upon saMVA WT vaccination. Referring to Figure 18, it is similarly shown that the number of poxvirus-specific CD8 T cells positive for IFN-γ and CD107 or TNFα increases upon saMVA WT vaccination. Example 10 - Immune gene expression of IFN-β, CXCL10, and ISG15 upon delivery of saMVA and derivatives thereof onto human foreskin fibroblasts As previously discussed, the inventors have produced two additional vectors according to the invention further to saMVA WT and saMVA CI, which may be referred to herein as saMVA-M (specifically R255E and NN153 / 154AA), and tested their efficacy in human fibroblasts against that of standard MVA and saMVA. R255E and NN153 / 154AA (i.e., the saMVA-Ms) differ from saMVA WT and saMVA CI in that they comprise a mutant copy of the cGAS gene (cGAS R255E or cGAS NN153 / 154AA), which render the cGAS enzyme more stable. These cGAS mutants cannot be degraded by a cell, and the inventors predict that they may, therefore, trigger stronger responses. Furthermore, carrying such cGAS mutants render these saMVA variants more stable in cells. Referring to Figure 19, it is shown that responses to R255E and NN153 / 154AA were enhanced relative to MVA and even relative to saMVA. Notably, each of saMVA, R255E, and NN153 / 154AA showed efficacy in human fibroblasts, as indicated by the increased expression of IFN-β, CXCL10, and ISG15. Indeed, the results shown in Figure 19 again confirm the superior ability of saMVA, over standard MVA, to induce type I interferon responses. In addition, the results display how this superior ability to induce type I interferon responses is retained, and in some cases enhanced, by saMVA vectors carrying mutants of cGAS that have higher stability in cells. Discussion Taken together, the data presented in the Examples demonstrate that MVA encoding a copy of cGAS, used herein by the inventors as a proof-of-concept for a cytosolic- replicating DNA viral vector encoding a cyclic di-nucleotide synthetase enzyme, is capable of enhanced activation of innate immune sensing compared to conventional MVA, i.e., a non-self-adjuvanting vector. This validates the inventors’ rationale that delivery of a pattern recognition receptor (PRR), i.e., cGAS, during infection would enhance the sensing of the attenuated viral vector and enhance STING-dependent signalling. Both saMVA WT and saMVA CI have demonstrated enhanced activation of antiviral signalling pathways and production of interferons, which have been demonstrated to enhance recruitment of the adaptive immune response in vivo (18). Notably, the catalytically inactive cGAS encoded by saMVA CI still enhances the activation of the cGAS / STING pathway, and this is thought to be mediated by the retained ability to enhance liquid phase condensation of the endogenous cGAS in the target cell, which is an important facet of cGAS function which increases the production of 2’3’-cGAMP (19). There have been many strategies attempted to enhance the immunogenicity of MVA, and thus its suitability as a platform for vaccine development; these include strategies to delete immunomodulators to enhance sensing by endogenous innate immune factors (20–23), or encoding host immune factors to enhance immune signalling (24). However, these strategies are stymied by the lack of productive replication in mammalian cells by MVA limiting the number of cells which are infected and therefore able to respond to the vaccination, which can be seen by the greater immune response to replication competent VACV (25). The inventors’ innovative saMVA strategy, as disclosed herein, addresses this limitation by inducing production of the immunotransmitter cGAMP, which is capable of inducing production of interferon in bystander cells (17); this increases the number of cells which will produce interferons to induce an adaptive immune response instead of only increasing the magnitude of the response in directly infected cells. The viruses were tested in vivo by assessing the ability of splenocytes to respond to a cocktail of poxviral antigens 7 days post-vaccination, which is a standard time point used to assess the immunogenicity of MVA (25, 26). The splenocytes harvested from animals inoculated with saMVA WT and saMVA CI both demonstrated increased response to the poxviral peptide cocktail compared to FMVA-Ctrl. These results indicate that the inventors’ saMVA strategy is capable of inducing a greater T cell response than conventional MVA strains in vivo, and can be considered as a vaccine platform for poxviruses, among other pathogens. Conclusions Overall, the inventors have shown that delivery of a cyclic di-nucleotide synthetase enzyme gene, such as cGAS, to target cells in a cytosolic-replicating vaccine vector, such as MVA, is a viable strategy for enhancing the induction of innate immune signalling in not only directly infected cells, but also in bystander cells. This enhanced signalling has been demonstrated to lead to robust production of important cytokines, such as IFN-β and the immunotransmitter 2’3’-cGAMP, in vitro. Hence, this strategy offers a solution to enhance the immune activation and immunogenicity of vaccines and therapeutic vectors, paving the way for a new generation of vaccines. References 1. Mahnel H, Mayr A. 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One- and Two-Dose Vaccinations With Modified Vaccinia Ankara-Bavarian Nordic Induce Durable B-Cell Memory Responses Comparable to Replicating Smallpox Vaccines. J Infect Dis.2023 May 12;227(10):1203–13. 9. Unterholzner L, Sumner RP, Baran M, Ren H, Mansur DS, Bourke NM, et al. Vaccinia virus protein C6 is a virulence factor that binds TBK-1 adaptor proteins and inhibits activation of IRF3 and IRF7. PLoS Pathog. 2011 Sep;7(9):e1002247. 10. Yang N, Wang Y, Dai P, Li T, Zierhut C, Tan A, et al. Vaccinia E5 is a major inhibitor of the DNA sensor cGAS. Nat Commun [Internet].2023;14(1):2898. Available from: https: / / doi.org / 10.1038 / s41467-023-38514- 5 11. Meade N, King M, Munger J, Walsh D. mTOR Dysregulation by Vaccinia Virus F17 Controls Multiple Processes with Varying Roles in Infection. J Virol.2019 Aug;93(15). 12. Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. 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Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. PLoS One. 2012;7(2):e32220. 22. Holgado MP, Falivene J, Maeto C, Amigo M, Pascutti MF, Vecchione MB, et al. Deletion of A44L, A46R and C12L Vaccinia Virus Genes from the MVA Genome Improved the Vector Immunogenicity by Modifying the Innate Immune Response Generating Enhanced and Optimized Specific T-Cell Responses. Viruses.2016 May 23;8(5). 23. Rehm KE, Roper RL. Deletion of the A35 gene from Modified Vaccinia Virus Ankara increases immunogenicity and isotype switching. Vaccine [Internet].2011;29(17):3276–83. Available from: https: / / www.sciencedirect.com / science / article / pii / S0264410X11002362 24. Falqui M, Perdiguero B, Coloma R, Albert M, Marcos-Villar L, McGrail JP, et al. An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses. Front Cell Infect Microbiol.2023;13:1187193. 25. Russell TA, Tscharke DC. 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Claims

Claims 1. A recombinant vector comprising a cytosolic-replicating DNA virus encoding at least one cyclic di-nucleotide synthetase enzyme.

2. The recombinant vector according to claim 1, wherein the cytosolic-replicating DNA virus is selected from the group of viruses consisting of: a poxvirus, an asfarvirus, and an iridovirus.

3. The recombinant vector according to claim 2, wherein: (i) the asfarvirus is African swine fever virus (ASFV); and / or (ii) the poxvirus is selected from a group of poxviruses consisting of: Avipoxvirus, Capripoxvirus, Centapoxvirus, Cervidpoxvirus, Crocodylidpoxvirus, Leporipoxvirus, Macropopoxvirus, Molluscipoxvirus, Mustelpoxvirus, Orthopoxvirus, Oryzopoxvirus, Parapoxvirus, Pteropopoxvirus, Salmonpoxvirus, Sciuripoxvirus, Suipoxvirus, Vespertilionpoxvirus, Yatapoxvirus, Alphaentomopoxvirus, Betaentomopoxvirus, Deltaentomopoxvirus, Diachasmimorpha entomopoxvirus, and Gammaentomopoxvirus.

4. The recombinant vector according to claim 3, wherein: (i) the Avipoxvirus is selected from a group of Avipoxviruses consisting of: fowlpox virus, pigeonpox virus, and canarypox virus; and / or (ii) the Orthopoxvirus is selected from a group of Orthopoxviruses consisting of: Camelpox virus, Cowpox virus, Ectromelia virus, Horsepox virus, Monkeypox virus, Raccoonpox virus, Skunkpox virus, Taterapox virus, Uasin Gishu virus, Vaccinia virus, Variola virus, and Volepox virus.

5. The recombinant vector according to claim 1, wherein the virus is derived from a Vaccinia virus strain, optionally wherein the Vaccinia virus strain is selected from a group of Vaccinia virus strains consisting of: NYVAC, Western Reserve (WR), Lister (and derivatives LC16m0 and LC16m8), Wyeth, Bern, Ankara, Tian-Tian, Ikeda, and Modified vaccinia Ankara (MVA).

6. The recombinant vector according to claim 1, wherein the virus is derived from a Vaccinia virus strain, wherein the Vaccinia virus strain is Modified vaccinia Ankara (MVA).

7. The recombinant vector according to any preceding claim, wherein the recombinant vector comprises a cytosolic-replicating DNA viral genome.

8. The recombinant vector according to any preceding claim, wherein the at least one cyclic di-nucleotide synthetase enzyme is derived from an animal, bacteria, fungus, or virus, optionally wherein the cyclic di-nucleotide synthetase enzyme is derived from a mammal.

9. The recombinant vector according to any preceding claim, wherein the at least one cyclic di-nucleotide synthetase enzyme is selected from the group of cyclic di- nucleotide synthetase enzymes consisting of: cyclic GTP-ATP synthase (cGAS), deadenylate cyclase (DAC), DncV, Hypr-GGDEF, DisA, and diguanylate cyclase (DGC).

10. The recombinant vector according to any preceding claim, wherein the at least one cyclic di-nucleotide synthetase enzyme is cyclic GTP-ATP synthase (cGAS).

11. The recombinant vector according to any preceding claim, wherein: (i) the at least one cyclic di-nucleotide synthetase enzyme comprises an amino acid sequence substantially as set out in SEQ ID No: 1, or a fragment or variant thereof; and / or (ii) the at least one cyclic di-nucleotide synthetase enzyme is encoded by a nucleic acid sequence substantially as set out in SEQ ID Nos: 2 or 5, or a fragment or variant thereof.

12. The recombinant vector according to any one of claims 1 to 10, wherein: (i) the at least one cyclic di-nucleotide synthetase enzyme comprises an amino acid sequence substantially as set out in SEQ ID No: 3, or a fragment or variant thereof; and / or (ii) the at least one cyclic di-nucleotide synthetase enzyme is encoded by a nucleic acid sequence substantially as set out in SEQ ID Nos: 4 or 6, or a fragment or variant thereof.

13. The recombinant vector according to any one of claims 1 to 10, wherein: (i) the at least one cyclic di-nucleotide synthetase enzyme comprises an amino acid sequence substantially as set out in SEQ ID Nos: 28 or 30, or a fragment or variant thereof; and / or(ii) the at least one cyclic di-nucleotide synthetase enzyme is encoded by a nucleic acid sequence substantially as set out in SEQ ID Nos: 29 or 31, or a fragment or variant thereof, optionally wherein the recombinant vector comprises at least one gene encoding a cyclic di-nucleotide synthetase enzyme.

14. The recombinant vector according to any preceding claim, wherein the recombinant vector encodes between two and 25 cyclic di-nucleotide synthetase enzymes, optionally wherein: (i) the cyclic di-nucleotide synthetase enzymes comprise the same cyclic di-nucleotide synthetase enzyme or different cyclic di-nucleotide synthetase enzymes; and / or (ii) the genes encoding the cyclic di-nucleotide synthetase enzymes are in tandem.

15. The recombinant vector according to any preceding claim, wherein the gene encoding the at least one cyclic di-nucleotide synthetase enzyme is operatively linked to a transcriptional and / or translational regulatory sequence, optionally wherein the transcriptional and / or translational regulatory sequence comprises a promoter, enhancer, silencer, operator, 5’ untranslated region (UTR), and / or 3’ UTR.

16. The recombinant vector according to claim 15, wherein the transcriptional and / or translational regulatory sequence comprises a viral promoter and / or an operator, optionally wherein the viral promoter is selected from a group of viral promoters consisting of: p7.5 promoter, pE / L, mH5, pF13L, and p4b.

17. The recombinant vector according to either claim 15 or claim 16, wherein the promoter comprises a nucleotide sequence substantially as set out in SEQ ID Nos: 7 or 8, or a fragment or variant thereof.

18. The recombinant vector according to any one of claims 15 to 17, wherein the operator is selected from a group of operators consisting of: TetO, CuO, tamoxifen operators, light-switchable operators, and bacterial riboswitches.

19. The recombinant vector according to any preceding claim, wherein the recombinant vector further comprises at least one nucleic acid sequence which does not encode a cyclic di-nucleotide synthetase enzyme, optionally wherein theat least one nucleic acid sequence which does not encode a cyclic di-nucleotide synthetase enzyme encodes at least one therapeutic protein.

20. The recombinant vector according to claim 19, wherein the therapeutic protein comprises a protein or peptide derived from a pathogen, optionally wherein: (i) the protein or peptide is derived from a bacteria, virus, fungus, protozoa, or parasite; and / or (ii) the protein or peptide is an antigen.

21. The recombinant vector according to either claim 19 or claim 20, wherein the therapeutic protein comprises a cancer immunogen or antigen.

22. The recombinant vector according to any preceding claim, wherein: (i) the recombinant vector comprises a nucleic acid sequence substantially as set out in SEQ ID No: 11, or a fragment or variant thereof; and / or (ii) the recombinant vector comprises a nucleic acid sequence substantially as set out in SEQ ID No: 12, or a fragment or variant thereof.

23. The recombinant vector according to any preceding claim, wherein the at least one cyclic di-nucleotide synthetase enzyme detects and / or binds DNA, optionally wherein the at least one cyclic di-nucleotide synthetase enzyme detects and / or binds double stranded DNA (dsDNA).

24. The recombinant vector according to claim 23, wherein: (i) the dsDNA is located in the cytoplasm and / or nucleus; (ii) the dsDNA originates from the vector of the invention; and / or (iii) the dsDNA originates from the host cell, optionally wherein the dsDNA originating from the host cell originates from the nucleus or an organelle of the host cell.

25. The recombinant vector according to any preceding claim, wherein the at least one cyclic di-nucleotide synthetase enzyme produces a second messenger upon binding to dsDNA, optionally wherein: (i) the second messenger is immunogenic and / or has adjuvanting properties; and / or (ii) the second messenger is selected from a group consisting of: 2′3′ cyclic GMP–AMP (cGAMP), cyclic AMP, cyclic GMP, inositol triphosphate, diacylglycerol, and calcium.

26. A vaccine comprising the recombinant vector according to any one of claims 1-25.

27. The recombinant vector according to any one of claims 1-25, or the vaccine according to claim 26, for use in therapy.

28. The recombinant vector according to any one of claims 1-25, or the vaccine according to claim 26, for use in inducing or enhancing an immune response in a subject.

29. The recombinant vector for use according to claim 28, wherein the immune response comprises the innate immune response and / or the adaptive immune response.

30. The recombinant vector according to any one of claims 1-25, or the vaccine according to claim 26, for use in treating, preventing, or ameliorating an infectious disease or cancer.

31. A pharmaceutical composition comprising the recombinant vector according to any one of claims 1-25, or the vaccine according to claim 26, and a pharmaceutically acceptable excipient.

32. A process for making the pharmaceutical composition according to claim 31, the process comprising combining a therapeutically effective amount of the vector according to any one of claims 1-25, or the vaccine according to claim 26, and a pharmaceutically acceptable vehicle.

33. A STING knockout cell line expressing a tetracycline repressor (TetR).

34. The STING knockout cell line according to claim 33, wherein the STING knockout cell line is an animal STING knockout cell line, an avian STING knockout cell line, a mammalian STING knockout cell line, a BHK21 STING knockout cell line, a HeLa STING knockout cell line, a CHO STING knockout cell line, a HEK STING knockout cell line, a DF-1 STING knockout cell line, a LMH STING knockout cell line, or an immortalised fibroblast STING knockout cell line.

35. The STING knockout cell line according to either claim 33 or claim 34, wherein the cell line is puromycin resistant.

36. Use of the STING knockout cell line according to any one of claims 33-35 for producing the vector according to any one of claims 1-25.

37. A method of producing the vector according to any one of claims 1-25, the method comprising culturing the STING knockout cell line according to any one of claims 33-35, to thereby produce the vector of any one of claims 1-25.

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