RESUMO
The most important targets for vaccine development are the proteins that are highly expressed by the microorganisms during infection in-vivo. A number of Mycobacterium tuberculosis (Mtb) proteins are also reported to be expressed in-vivo at different phases of infection. In the present study, we analyzed multiple published databases of gene expression profiles of Mtb in-vivo at different phases of infection in animals and humans and selected 38 proteins that are highly expressed in the active, latent and reactivation phases. We predicted T- and B-cell epitopes from the selected proteins using HLAPred for T-cell epitope prediction and BCEPred combined with ABCPred for B-cell epitope prediction. For each selected proteins, regions containing both T- and B-cell epitopes were identified which might be considered as important candidates for vaccine design against tuberculosis.
Assuntos
Proteínas de Bactérias/genética , Biologia Computacional , Epitopos de Linfócito B/genética , Epitopos de Linfócito T/genética , Mycobacterium tuberculosis/genética , Tuberculose/genética , Animais , Proteínas de Bactérias/imunologia , Bases de Dados Genéticas , Desenho de Fármacos , Regulação Bacteriana da Expressão Gênica , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/patogenicidade , Redes Neurais de Computação , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/imunologiaRESUMO
BACKGROUND: Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. METHODS: The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. RESULTS: The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. CONCLUSION: The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice.
Assuntos
Terapia por Estimulação Elétrica/métodos , Neoplasias/terapia , Animais , Linhagem Celular Tumoral , Fibrossarcoma/metabolismo , Humanos , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Modelos Estatísticos , Modelos Teóricos , Neoplasias/patologia , Indução de Remissão , Fatores de TempoRESUMO
The lipopolysaccharide (LPS) of Vibrio cholerae is considered one of the most important antigens from the point of view of immunogenicity in these bacteria. We have undertaken detoxification of this LPS by basic hydrolysis and the resultant amine groups were used for their conjugation to tetanus toxoid as carrier protein using carbodiimide-mediated coupling. The resulting conjugates were inoculated in Balb/c mice for immunogenicity studies. The anti-LPS IgG and vibriocidal antibodies were measured in serum. The antigenicity of this conjugated was evaluated by ELISA, with serums of humans vaccinated with a strain genetically modified. The conjugated elicited: high titers of IgG anti-LPS, high titers of vibriocidal antibodies and there was recognition of LPS by antibodies from cholerae immunised human serum. These results show that the conjugated LPS obtained by us, could be evaluated like a potential vaccine for human use.
