Chimeric DNA Vaccine Design

Creative Biolabs is a world leader in the field of cancer vaccine development. With our extensive experience and advanced platform, we are therefore confident in offering the best development services of chimeric DNA vaccines for cancer. We guarantee the finest results for our customers all over the world.

Why Use Chimeric DNA Vaccine

Several studies have demonstrated that self-reactive antibodies are better induced by autologous rather than xenogeneic vaccination, reflecting the exquisite specificity for the cognate antigen of antibodies induced by DNA vaccines. Therefore, one of the major issues concerning xenogeneic vaccination is the low-affinity antibody response generally induced against the self-homolog protein, thus limiting the anticancer efficacy of the vaccine.

Fig.1 Schematic representation of the mechanisms leading to the induction of potent cross-reactive T cell and antibody responses using chimeric proteins which combine xenogeneic and homologous domains of the self-oncoantigen.

One possible means by which to induce a combined potent cross-reactive T cell and antibody response is to use hybrid plasmids which code for chimeric proteins that include both xenogeneic and homologous oncoantigen domains. The potential efficacy of these plasmids relies on the presence of the homologous sequence which ensures the specificity of the immune response and the presence of the xenogeneic determinants which are instrumental in circumventing immune tolerance. In particular, the chimeric protein produced by transfected cells can be uptaken by DCs and also be recognized and internalized by B cells. In this way, peptides from both the xenogeneic and homologous domains of the internalized chimeric protein are presented by DCs and B cells through MHC class I (MHC I) and class II (MHC II) glycoproteins. The presentation of xenogeneic peptides by DCs is instrumental for the effective priming and the expansion of both CD8⁺ and CD4⁺ T cells which are specific for xenogeneic moieties and potentially cross-reactive against the homologous one. The interaction between the expanded CD4⁺ T cells with B cells, which recognize the xenogeneic domain of the chimeric protein, leads to the differentiation of plasma cells which produce antibodies which are specifically against the xenogeneic domain of the vaccine. By contrast, the interaction of expanded CD4⁺ T cells with B cells which recognize the homologous domain leads to the production of antibodies which are specific for the self-tolerated homologous domain of the protein, by differentiated plasma cells. The slight differences in the amino acid sequence and in the tertiary structure of the chimeric protein, encoded by the hybrid plasmids, may result in the exposition of subdominant and/or new conformational epitopes, triggering an even more efficient humoral immune response than that induced by the xenogeneic and homologous vaccines.

Chimeric DNA Vaccine Design

• Seeing as the final goal of the hybrid plasmid strategy is the translation of chimeric vaccine into clinical practice, part of the antigen sequence must be derived from the human sequence.
• In general, a good degree of homology with the self-homologous oncoantigen can range from 85 to 95%.
• As far as the choice of species from which to derive the xenogeneic sequence used as the vaccine determinant is concerned, no defined indications are readily available. In principle, this heterologous sequence has to be different enough from that of the self-tolerated antigen in order to provide the heteroclitic peptides which are necessary to overcome T cell tolerance. However, it must, at the same time, be sufficiently similar to guarantee an effective cross-reactive immune response.
• Practically, the choice of the xenogeneic part, from the several options available, can be dictated by the preclinical model that will be used to evaluate the efficacy of the chimeric vaccine.
• Moreover, other important issues to take into consideration in the generation of effective vaccines are both the location of the autologous and the xenogeneic domains in the chimeric protein and the ability of the hybrid plasmid to give rise to a protein which presents a structural conformation which is similar to the homologous one.
• Finally, it has been suggested that vaccine-encoded specific homologous sequences may actually activate the Treg population, thus limiting vaccine-induced anti-tumor immune response. Therefore, when designing a hybrid plasmid for a given oncoantigen, self-regions involved in Treg expansion should be defined and replaced with the corresponding xenogeneic sequences.

Based on all previous considerations, the design of hybrid vaccines which target oncoantigens should be theoretically performed once the critical regions for immune activation in the self and in the heterologous antigens have been clearly defined.

Creative Biolabs is a leader in the field of vaccine development and has focused on the cancer vaccines for years. We have experienced experts and advanced platforms that are able to provide excellent services. If you are interested in our services, please contact us for more details.

All of our products can only be used for research purposes. These vaccine ingredients CANNOT be used directly on humans or animals.