RESUMEN
The development of vaccines against a wide range of infectious diseases and pathogens often relies on multi-epitope strategies that can effectively stimulate both humoral and cellular immunity. Immunoinformatics tools play a pivotal role in designing such vaccines, enhancing immune response potential, and minimizing the risk of failure. This review presents a comprehensive overview of practical tools for epitope prediction and the associated immune responses. These immunoinformatics tools facilitate the selection of epitopes based on parameters such as antigenicity, absence of toxic and allergenic sequences, secondary and tertiary structures, sequence conservation, and population coverage. The chosen epitopes can be tailored for B-cells or T-cells, both of which require further assessments covered in this study. We offer a range of suitable linkers that effectively separate cytotoxic T lymphocyte and helper T lymphocyte epitopes while preserving their functionality. Additionally, we identify various adjuvants for specific purposes. We delve into the evaluation of MHC-epitope interactions, MHC clusters, and the simulation of final constructs through molecular docking techniques. We provide diverse linkers and adjuvants optimized for epitope functions to bolster immune responses through epitope attachment. By leveraging these comprehensive tools, the development of multi-epitope vaccines holds the promise of robust immunity and a significant reduction in experimental costs.
Asunto(s)
Biología Computacional , Epítopos de Linfocito T , Vacunas , Humanos , Biología Computacional/métodos , Vacunas/inmunología , Epítopos de Linfocito T/inmunología , Animales , Simulación por Computador , Adyuvantes Inmunológicos , Simulación del Acoplamiento Molecular , Epítopos de Linfocito B/inmunología , Epítopos/inmunología , Desarrollo de VacunasRESUMEN
Zika virus (ZIKV) is an emerging virus from the Flaviviridae family and Flavivirus genus that has caused important outbreaks around the world. ZIKV infection is associated with severe neuropathology in newborns and adults. Until now, there is no licensed vaccine available for ZIKV infection. Therefore, the development of a safe and effective vaccine against ZIKV is an urgent need. Recently, we designed an in silico multi-epitope vaccine for ZIKV based on immunoinformatics tools. To construct this in silico ZIKV vaccine, we used a consensus sequence generated from ZIKV sequences available in databank. Then, we selected CD4+ and CD8+ T cell epitopes from all ZIKV proteins based on the binding prediction to class II and class I human leukocyte antigen (HLA) molecules, promiscuity, and immunogenicity. ZIKV Envelope protein domain III (EDIII) was added to the construct and B cell epitopes were identified. Adjuvants were associated to increase immunogenicity. Distinct linkers were used for connecting the CD4+ and CD8+ T cell epitopes, EDIII, and adjuvants. Several analyses, such as antigenicity, population coverage, allergenicity, autoimmunity, and secondary and tertiary structures of the vaccine, were evaluated using various immunoinformatics tools and online web servers. In this chapter, we present the protocols with the rationale and detailed steps needed for this in silico multi-epitope ZIKV vaccine design.
Asunto(s)
Infección por el Virus Zika , Virus Zika , Recién Nacido , Humanos , Virus Zika/genética , Infección por el Virus Zika/prevención & control , Epítopos de Linfocito T , Epítopos de Linfocito B , Proteínas del Envoltorio Viral , Biología Computacional/métodos , Simulación del Acoplamiento MolecularRESUMEN
Human papillomaviruses (HPV)-16 and 18 are the most prevalent types associated with cervical cancer. HPV L1 and L2 capsid proteins and E7 oncoprotein play crucial roles in HPV-related diseases. Hence, these proteins were proposed as target antigens for preventive and therapeutic vaccines. In this study, two multiepitope DNA-based HPV vaccine candidates were designed using in silico analysis including the immunogenic and conserved epitopes of HPV16/18 L1, L2 and E7 proteins (the L1-L2-E7 fusion DNA), and of heat shock protein 70 (HSP70) linked to the L1-L2-E7 DNA construct (the HSP70-L1-L2-E7 fusion DNA). Next, the expression of the L1-L2-E7 and HSP70-L1-L2-E7 multiepitope DNA constructs was evaluated in a mammalian cell line. Finally, immunological responses and antitumor effects of the DNA constructs were investigated in C57BL/6 mice. Our data indicated high expression rates of the designed multiepitope L1-L2-E7 DNA (~ 56.16%) and HSP70-L1-L2-E7 DNA (~ 80.45%) constructs in vitro. The linkage of HSP70 epitopes to the L1-L2-E7 DNA construct significantly increased the gene expression. Moreover, the HSP70-L1-L2-E7 DNA construct could significantly increase immune responses toward Th1 response and CTL activity, and induce stronger antitumor effects in mouse model. Thus, the designed HSP70-L1-L2-E7 DNA construct represents promising results for development of HPV DNA vaccine candidates.