VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases
2. Application of the Use of VLPs in the Development of New Vaccines
3. Vaccines to Control Diseases Caused by Trypanosomatids: What Do We Need and Where Are We?
4. Development of Vaccines Based on VLPs: A Checklist
- Should the chosen virus be enveloped or not? Enveloped VLPs are inherited from structured viral proteins, thus generating a particle with target antigens integrated on the external surface, whereas non-enveloped VLPs are based on the expression of one or more necessary viral proteins without inheriting them from a host . Both have the additional possibility to integrate antigens  and additional adjuvants  in vaccine formulations.
- Which expression system is ideal? It should be noted that, depending on the system, there will be limitations such as cost and difficulty in scheduling , as well as a higher level of purification when faced with contamination from cells . Some systems differ from mammalian cells mainly in the protein glycosylation phase  and do not give rise to a eukaryotic expression environment. The insect cell system has come to solve some problems in the production of particulates, as it has characteristics such as a eukaryotic environment, which is required for the glycosylation of proteins: this post-translational characteristic is also found in human cells, but the cost of their application is higher . In addition, there is malleability in large-scale cultivation and the possibility of using it for the simultaneous expression of many proteins that facilitate the assembly of VLPs, which requires a structure with a high level of safety and a special culture system .
- The structural modification of the conformational and immunological characteristics of the VLP can adjust the relative degree of the immune response for a balanced induction of humoral and cellular immunity , thereby generating an improved candidate capable of redirecting the immune response against specific targets when combined with antigens . Thus, this modulates the balance of Th1 and Th2 immune responses to increase the specificity and affinity towards the parasite . Therefore, conformational changes and the aggregation of antigens are necessary to analyze changes in stability that can compromise the effectiveness of VLP vaccines .
- Before choosing the antigens, it is necessary to assess the immunological challenges found in the parasites that cause Chagas disease, leishmaniasis, and sleeping sickness. They have specific mechanisms of escape from the immune system that end up reducing the specific response of the immune system. Based on this assessment, one can then envision a single vaccine for three diseases or specific vaccines for each one, as VLPs will act as transporters of antigens, with greater security than using soluble antigens . The applicability of antigens presented in various evolutionary forms of the protozoan, as well as the attempt to administer immunizations with more than one antigen to cover all forms of life and increase the antigenic repertoire, must be considered in studies on T. cruzi, given the genetic variability of this parasite . In addition, the use of the same antigens for both prophylactic and therapeutic strategies should be considered, taking into account that prophylactic and therapeutic vaccines can prevent infection and interfere with the progression of infection, respectively. For an infected person, a therapeutic vaccine with or without an association with available drugs can have a significant impact on preventing complications, as has already been reported for Chagas disease .
- After the production and necessary testing of these particles in isolation and in association with antigens, in vitro and in vivo tests need to be performed, for example, endotoxin evaluation . In addition, a basic toxicity assessment must be performed, according to the WHO guidelines for non-clinical evaluation of vaccines . This step can also assist in understanding the humoral and cellular immunogenicity of the isolated particles without antigen association. The choice of adjuvant must include consideration of the cost–benefit trade-off of co-stimulation, as VLPs can assume the role of self-adjuvant due to their particulate and multivalent nature, causing efficient incorporation by antigen-presenting cells (APCs) [69,70].
- In vivo tests on immunization strategies with these specific antigens and/or with a chimeric VLP should be performed by firstly establishing the animal model, time, and doses, characterizing the humoral and cellular immune responses, and importantly, considering different routes of administration to understand whether this influences the stability of VLPs .
- Viral challenges in animals (experimental infection) used in experiments are necessary to understand, for example, whether the formulation of specific antigens with VLP technology helps or not in the survival of those infected. After pre-clinical trials proceed as expected, clinical trials have a significant step in producing results that confirm a specific, lasting, and harmless response in humans.
5. Final Considerations and Conclusions
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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Queiroz, A.M.V.; Oliveira, J.W.d.F.; Moreno, C.J.; Guérin, D.M.A.; Silva, M.S. VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases. Vaccines 2021, 9, 220. https://doi.org/10.3390/vaccines9030220
Queiroz AMV, Oliveira JWdF, Moreno CJ, Guérin DMA, Silva MS. VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases. Vaccines. 2021; 9(3):220. https://doi.org/10.3390/vaccines9030220Chicago/Turabian Style
Queiroz, Aline Maria Vasconcelos, Johny Wysllas de Freitas Oliveira, Cláudia Jassica Moreno, Diego M. A. Guérin, and Marcelo Sousa Silva. 2021. "VLP-Based Vaccines as a Suitable Technology to Target Trypanosomatid Diseases" Vaccines 9, no. 3: 220. https://doi.org/10.3390/vaccines9030220