RESUMO
Dengue is a major worldwide public health problem, especially in the tropical and subtropical regions of the world. Primary infection with a single Dengue virus (DENV) serotype causes a mild, self-limiting febrile illness called dengue fever. However, a subset of patients experiencing a secondary infection with a different serotype progress to the severe form of the disease, called dengue hemorrhagic fever. In this study, the vaccine potential of three tetravalent and conserved synthetic peptides derived from DENV envelope domain I (named Pep01) and II (named Pep02 and Pep03) was evaluated. Human dengue IgM/IgG positive serum (n=16) showed reactivity against Pep01, Pep02 and Pep03 in different degrees. Mice immunization experiments showed that these peptides were able to induce a humoral response characterized by antibodies with low neutralizing activity. The spleen cells derived from mice immunized with the peptides showed a significant cytotoxic activity (only for Pep02 and Pep03), a high expression of IL-10 (P<0.01) and a reduced expression of TNF-α and IFN-gamma (P<0.001) compared to DENV-1 infected splenocytes. Thus these peptides, and specially the Pep03, can induce a humoral response characterized by antibodies with low neutralizing activities and probably a T cell response that could be beneficial to induce an effective immune response against all DENV serotypes and do not contributed to the immunopathogenesis. However, further studies in peptide sequence will be required to induce the production of neutralizing antibodies against all four DENV serotypes and also to improve immunogenicity of these peptides.
Assuntos
Vacinas contra Dengue/imunologia , Vírus da Dengue/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Testes Imunológicos de Citotoxicidade , Vacinas contra Dengue/administração & dosagem , Vacinas contra Dengue/genética , Vírus da Dengue/genética , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Camundongos , Testes de Neutralização , Linfócitos T Citotóxicos/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia , Proteínas do Envelope Viral/genéticaRESUMO
Pseudomonas aeruginosa is an important opportunistic human pathogen that causes severe infections in immunocompromised patients and also in cystic fibrosis patients. The aim of this work was to study if a bovine serum albumin nanoparticles with entrapped antigens extracted from P. aeruginosa would be able to protect mice from nasal infection by this pathogen. Mice were immunized via the subcutaneous route using P. aeruginosa antigens, empty nanoparticles or nanoparticles with entrapped P. aeruginosa antigens on days 0, 7 and 14. The total IgG antibody production and specific IgG1 and IgG2a titer were measured by ELISA. Immunized mice were challenged with live P. aeruginosa and their lungs were collected for histopathology studies. Our data showed that NPPa-vaccinated mice presented a high anti-Pseudomonas IgG1 and a low IgG2a antibody titles and decreased inflammatory signs, with significant reduction in intensity and concentration of inflammatory cells, lower hemorrhagic, edema and hyperemia signs in the lungs of challenge mice with live P. aeruginosa if compared to the other groups. Therefore, this formulation is able to induce a functional response in an animal model of infection and thereby is a promising platform for P. aeruginosa vaccines.