In the Reverse Vaccinology method, which we select the Immunodominant peptides based on the In slico method, and since the initial stage is working on the mouse, we must select a peptide that can efficiently be connected to the mouse MHC. If this is indeed the case and selected peptide induced an effective response in the mice. Next, if we want to enter the clinical trial phases on humans, since we have chosen the peptide specifically for mouse MHC, is that peptide also work on human MHC as an immunodominant? Or, like the mouse, can we have an effective response in this case?
Whole-genome sequencing of bacteria and advances in bioinformatics have revolutionized the vaccinology field, leading to the identification of potential vaccine candidates without the need for cultivating the pathogen. This approach, termed "reverse vaccinology", reduces the time and cost required for the identification of candidate vaccines and provides new solutions for those diseases for which conventional approaches have failed. The first example of the potential of reverse vaccinology has been the identification of novel antigens of meningococcus B as potential candidates for a novel and effective vaccine. The same approach has been successfully applied to other important human pathogens, demonstrating the feasibility to develop vaccines against any infectious disease. This review focuses on some recent advances in the identification of vaccine candidates by mining the genomic sequences of pathogenic bacteria.
Take a look in the tools NetMHC / NetMHCII por the identification of sites that might be selected by these classes of MHC in your set of proteins (eg: expected proteome). There is also other tools, such as predictors of B-Cell / T-Cell epitopes, that are also interesting. I would also suggest you take a look at the software MED (Mature Epitope Density), which is very interesting to rank proteins based on in silico-predicted immunogenicity.
This question is very interesting. Reverse vaccination is in my mind a method to understand the different events of the immunological response. Whereas retro vaccination seeks to reproduce a highly targeted immune response. In the first case, the reverse vaccination can be applied to all animal species, without restriction. In the second case, retro vaccination is, as you point out, species-specific and can not be transposed from the mouse to humans, for a whole bunch of reasons. The case of MHC I and II is indeed essential. Just as the choice of so-called dominant epitopes (I do not know what it means), so is it. For the choice of the epitope, it requires to discover an antibody of very high affinity, able to perfectly neutralize the targeted pathogen (the in silico method does not really work). It is then necessary to identify the recognized epitope, which is generally conformational. Then we must be able to reproduce it, the Aptamer method being the most effective one. This question is very interesting. Reverse vaccination is in my mind a method to understand the different events of the immunological response. Whereas retro vaccination seeks to reproduce a highly targeted immune response. In the first case, the reverse vaccination can be applied to all animal species, without restriction. In the second case, retro vaccination is, as you point out, species-specific and can not be transposed from the mouse to humans, for a whole bunch of reasons. The case of MHC I and II is indeed essential. Just as the choice of so-called dominant epitopes (I do not know what it means), so is it. For the choice of the epitope, it requires to discover an antibody of very high affinity, able to perfectly neutralize the targeted pathogen (the in silico method does not really work). It is then necessary to identify the recognized epitope, which is generally conformational. Then we must be able to reproduce it, the Aptamer method being the most effective one.
In fact, I never managed to protect an individual by vaccinating with a peptide that reproduced the sequence of a conformational epitope. The reason is that whatever the immune system does the individual repackages the peptide to present it via MHC I and then MHC II to the immunocompetent cells that are dendritic cells. I tried to extend the peptide sequence so that it can be processed by the capture DCs (lang +, DCSign +, MR + ....) so that the newly formed epitopes are presented to the TCD4 + cells and then to the B cells, via presentation DCs (DCIR +, FDFO3 +, CD21L + ...). In the end, we always get random results, which are species depend. What will work in mice, does not give the same efficiency in the rat or the dog. And even less in humans. This comes mainly from the species variability of capture molecules (eg langerin), and targeting (Ex: DCIR). And unfortunately, we have not yet been able to predict it in silico.
Im currently working on an in silico design of methicillin-resistant Staphylococcus aureus whole genome based vaccine. Using reverse vaccinology and I finished the steps of reverse vaccinology with a 27 filtered protein candidates for vaccine construction. I'm asking about that which proteins should I work on out of the 27 proteins. On what basic should I choose the candidates for bcell and t cell epitope prediction and the subsequent steps.
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biomolecules
- Peptides