The period between 2011-2020 has been designated by WHO the Decade of Vaccines . In addition to the eradication of poliomyelitis, the reduction of child mortality and other goals of prime interest, special focus is given to the development and introduction of new and improved vaccine technologies.
Since the first vaccines that contained attenuated or dead microorganisms a series of discoveries led to the concept of third generation vaccines that are safe and can induce long term protection against infections. These new insights, which also enabled development of the principles for therapeutic vaccines against cancer, were the following:
- Part of the microorganism is sufficient to generate an adequate immune response, moreover, a DNA sequence encoding the production of a protein specific to the given microorganism can also lead to the activation of the immune system. The benefit of this solution is the fast, cheap and safe production of the antigen in the form of a DNA sequence in comparison to using the whole pathogen.
- Some cancer antigens have been identified that allow for the prevention or immunotherapy of specific tumours.
- Specific auxiliary substances called adjuvants are needed to enhance the reaction of the body to antigens. Without adjuvants, antigens can be degraded and eliminated from the body or the immune response against the antigen is too weak. This is especially applicable to cancer antigens, which are recognized by the body as endogenous (like the body itself) and as result the production of killer cells against them is reduced.
- Adjuvants can be, for example, short DNA fragments of the bacterial or viral genome that are recognized as dangerous intruders. One promising type of adjuvants are CpG ODNs (OligoDeoxyNucleotides with CpG motifs) that are particularly suitable inducing strong immune responses against tumor cells and thus are used as adjuvants in cancer vaccine development.
- Small vehicles such as microparticles and even smaller nanoparticles have an intrinsic additional adjuvant effect due to their size, which is similar to the size of pathogens. This effect is independent of the material of the particles. Furthermore, small carriers can bind and transport several adjuvants and antigens on their surface presenting them together to immune cells.
- Immune cells recognize the nanoparticles as intruders, engulf them and take them up into specific organelles. As a result, the nanocarriers quickly accumulate in the immune cells and deliver the antigen and the adjuvant to their target cell, where they can launch the immune response.
Objectives
Based on this framework, our project aimed at the preparation of new type of nanoparticles that can readily bind CpG ODN adjuvants on their surface and can potentially become potent adjuvant nanocarriers for cancer vaccination. The scientific objectives were:
1. elaboration of the new nanocarriers
2. application of nuclear magnetic resonance techniques to confirm the binding of oligonucleotides at the surface of the nanocarriers and to characterize the interaction
3. preliminary evaluation of the new nanocarriers in biological assays that would tell us, if our product has an added value in comparison to the CpG ODN adjuvant alone.
