Laboratório de Vacinas, Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Departamento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Minas Gerais, Brazil.
Virus Res. 2014 Aug 8;188:122-7. doi: 10.1016/j.virusres.2014.04.009. Epub 2014 Apr 21.
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.
登革热是一个全球性的主要公共卫生问题，尤其是在世界的热带和亚热带地区。初次感染单一血清型登革病毒（DENV）会导致轻度、自限性发热疾病，称为登革热。然而，一部分患者会发生不同血清型的二次感染，发展为严重疾病，称为登革出血热。在这项研究中，评估了三种源自登革病毒包膜域 I（命名为 Pep01）和 II（命名为 Pep02 和 Pep03）的四价且保守的合成肽的疫苗潜力。人类登革热 IgM/IgG 阳性血清（n=16）显示出对 Pep01、Pep02 和 Pep03 的不同程度的反应性。小鼠免疫实验表明，这些肽能够诱导以低中和活性抗体为特征的体液反应。与 DENV-1 感染的脾细胞相比，用这些肽免疫的小鼠脾细胞显示出显著的细胞毒性活性（仅针对 Pep02 和 Pep03）、高水平的 IL-10（P<0.01）和低水平的 TNF-α和 IFN-γ（P<0.001）。因此，这些肽，特别是 Pep03，可以诱导以低中和活性抗体为特征的体液反应，并可能诱导 T 细胞反应，这可能有助于诱导针对所有 DENV 血清型的有效免疫反应，而不会导致免疫病理发生。然而，需要进一步研究肽序列以诱导针对所有四种 DENV 血清型的中和抗体的产生，并提高这些肽的免疫原性。
