RESUMO
Human papillomavirus (HPV) represents the most prevalent sexually transmitted infectious agent worldwide. Vaccination has been an approach successfully used as a prophylactic measure against this infectious agent in patients without previous contact with the genotypes present in the vaccine. In this work, we use a computational approach to predict CD8 T cell epitopes from HPV proteins to promote cell-mediated immunity. We evaluated immunogenicity, conservation, toxicity, stability and population coverage of epitopes. Finally, a molecular docking analysis was performed to confirm the stability of the complexes formed. We identified 17 epitopes with affinity for several HLA alleles, covering 5 binding supermotifs (A2, A3, A24, B62 and B57). The analyses showed that these epitopes have a high population coverage and are highly conserved among several HPV genotypes. Seven of them (NWKNFFSTTWE1594-603, KVSAFQYRVFRVL163-74, LQFIFQLCKL1372-380, RVFRVQLPDPNKL170-81, FNKPYWLHRL1307-315, FITCVDTTRL1330-338 and HLRREQIFARL1248-257) were 100% conserved. Finally, molecular docking confirmed the stability of the complexes by means of a large network of hydrogen bonds formed and the calculated low bonding energy. The epitopes identified in this study are potential candidates as components of therapeutic vaccines and we suggest that these epitopes can be used in future studies aiming to activate antigen-specific CD8 T cells.
Assuntos
Epitopos de Linfócito T , Infecções por Papillomavirus , Linfócitos T CD8-Positivos , Biologia Computacional , Epitopos de Linfócito B , Humanos , Imunidade Celular , Simulação de Acoplamento Molecular , Infecções por Papillomavirus/prevenção & controleRESUMO
Vaccines against bovine babesiosis must, ideally, induce a humoral immune response characterized by neutralizing antibodies against conserved epitopes and a cellular Th1 immune response. In Babesia bovis, proteins such as AMA-1, MSA-2c, and RAP-1 have been characterized and antibodies against these proteins have shown a neutralizing effect, demonstrating the implication of B and T-cell epitopes in the immune response. There is evidence of the existence of B and T-cell epitopes in these proteins, however, it remains to be defined, the presence of conserved peptides in strains from around the world containing B and T-cell epitopes, and their role in the generation of a long-lasting immunity. The aim in this paper was to identify peptides of Babesia bovis AMA-1, MSA-2c, and RAP-1 that elicit a neutralizing and long-lasting Th1 immune response. Peptides containing B-cell epitopes of AMA-1, MSA-2c and RAP-1, were identified. The immune response generated by each peptide was characterized in cattle. All peptides tested induced antibodies that recognized intraerythrocytic parasites, however, only 5 peptides generated neutralizing antibodies in vitro: P2AMA-1 (6.28%), P3MSA-2c (10.27%), P4MSA-2c (10.42%), P1RAP-1 (32.45%), and P4RAP-1 (36.98%). When these neutralizing antibodies were evaluated as a pool, the inhibition percentage of invasion increased to 52.37%. When the T cellular response was evaluated, two peptides: P3MSA2c and P2AMA1 induced a higher percentage (>70%) of activated CD4 +/CD45RO+ T cells than unstimulated cells. Additionally, both peptides induced the production of gamma interferon (IFN-) in PBMCs from vaccinated cattle after one year proving the implication of a long-lasting Th1 immune response. In conclusion, we identified conserved peptides containing B and T-cell epitopes in antigens of B. bovis that elicit a Th1 immune response and showed evidence that peptides from the same protein elicit different immune responses, which has implication for vaccine development in bovine babesiosis.
Assuntos
Babesia bovis , Babesiose , Doenças dos Bovinos , Animais , Anticorpos Neutralizantes , Antígenos de Protozoários , Babesiose/prevenção & controle , Bovinos , Epitopos de Linfócito T , Imunidade Humoral , Proteínas de ProtozoáriosRESUMO
Leishmaniosis, caused by intracellular parasites of the genus Leishmania, has become a serious public health problem around the world, and for which there are currently extensive limitations. In this work, a theoretical model was proposed for the development of a multi-epitope vaccine. The protein GP63 of the parasite was selected for epitopes prediction, due to its important biological role for the infection process and abundance. IEDB tools were used to determine epitopes B and T in Leishmania braziliensis; besides, other conserved epitopes in three species were selected. To improve immunogenicity, 50S ribosomal protein L7 / L12 (ID: P9WHE3) was used as a domain of adjuvant in the assembly process. The folding arrangement of the vaccine was obtained through homologous modeling multi-template with MODELLER v9.21, and a Ramachandran plot analysis was done. Furthermore, physicochemical properties were described with the ProtParam tool and secondary structure prediction combining GOR-IV and SOPMA tools. Finally, a molecular dynamics simulation (50â¯ns) was performed to establish flexibility and conformational changes. The analysis of the results indicates high conservancy in the epitopes predicted among the four species. Moreover, Ramachandran plot, physicochemical parameters, and secondary structure prediction suggest a stable conformation of the vaccine, after a minimum conformational change that was evaluated with the free energy landscape. The conformational change does not drive any substantial change for epitope exposition on the surface. The vaccine proposed could be tested experimentally to guide new approaches in the development of pan-vaccines; vaccines with regions conserved in multiple species.
Assuntos
Leishmania/imunologia , Metaloendopeptidases/imunologia , Simulação de Dinâmica Molecular , Vacinas/imunologia , Epitopos/química , Epitopos/imunologia , Metaloendopeptidases/química , Conformação Proteica , Especificidade da EspécieRESUMO
Like other helminths, Trichinella spiralis has evolved strategies to allow it to survive in the host organism, including the expression of epitopes similar to those present in either expressed or hidden host antigens. To identify T. spiralis-derived antigens that are evolutionarily conserved in the parasite and its host and that could be responsible for its evasion of the host immune response, we examined the reactivity of six different types of autoantibodies to T. spiralis larvae from muscle. T. spiralis antigens that share epitopes with human autoantigens were identified by assessing the cross-reactivity of autoantibody-containing serum samples with T. spiralis antigens in the absence of specific anti-parasite antibodies. Of the 55 autoantibody-containing human serum samples that we analysed by immunohistological screening, 24 (43.6%) recognised T. spiralis muscle larvae structures such as the subcuticular region, the genital primordium or the midgut. Using Western blots, we demonstrated that the same sera reacted with 24 protein components of T. spiralis muscle larvae excretory-secretory L1 antigens. We found that the human autoantibodies predominantly bound antigens belonging to the TSL1 group; more specifically, the autoantibody-containing sera reacted most frequently with the 53-kDa component. Thus, this protein is a good candidate for further studies of the mechanisms of T. spiralis-mediated immunomodulation.