RESUMO
BACKGROUND: The arboviruses Zika virus (ZIKV) and Dengue virus (DENV) have important epidemiological impact in Brazil and other tropical regions of the world. Recently, it was shown that previous humoral immunity to DENV enhances ZIKV replication in vitro, which may lead to more severe forms of the disease. Thus, traditional approaches of vaccine development aiming to control viral infection through neutralizing antibodies may induce cross-reactive enhancing antibodies. In contrast, cellular immune response was shown to be capable of controlling DENV infection independently of antibodies. The aim of the present study was to design a flavivirus NS5 protein capable of inducing a cellular immune response against DENV and ZIKV. METHODS: A consensus sequence of ZIKV NS5 protein was designed among isolates from various continents. Epitopes were predicted for the most prevalent alleles of class I and II HLA in the Brazilian population. Then, this epitopes were analyzed with regard to their conservation, population coverage and distribution along the whole antigen. RESULTS: Nineteen epitopes predicted to be more reactive (percentile rank <1) and 100% conserved among ZIKV and DENV serotypes were selected. The distribution of such epitopes along the protein was shown on a three-dimensional model and population coverage was calculated for different regions of the world. The designed protein was predicted to be stable and the distribution of selected epitopes was shown to be homogeneous along domains. The population coverage of selected epitopes was higher than 50% for most of tropical areas of the world. CONCLUSION: Such results indicate that the proposed antigen has the potential to induce protective cellular immune response to ZIKV and DENV in different human populations of the world.
Assuntos
Vírus da Dengue/imunologia , Dengue/terapia , Imunidade Celular , Proteínas não Estruturais Virais/imunologia , Vacinas Virais/imunologia , Infecção por Zika virus/terapia , Zika virus/imunologia , Brasil , Simulação por Computador , Epitopos/imunologia , HumanosRESUMO
IMPORTANCE: Several additional COVID-19 vaccine doses were administered in the Brazilian population to prevent the disease caused by the B.1.1.529 (Omicron) variant. The efficacy of a third dose as a booster is already well described. However, it is important to clarify the humoral immune response gain induced by a fourth dose. In this study, we evaluate the effect of the fourth COVID-19 vaccine dose in a diverse Brazilian population, considering a real-life context. Our study reveals that the fourth dose of the COVID-19 vaccine increased the neutralizing antibody response against SARS-CoV-2 Omicron and significantly contributed in the reduction of the disease caused by this variant.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , SARS-CoV-2/genética , Brasil , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
BACKGROUND: Sexual dimorphism in animals has been studied from different perspectives for decades. In 1874 Darwin hypothesized that it was related to sexual selection, and even after nearly 140 years, when additional empirical data has become available and the subject has been investigated from a contemporary viewpoint, this idea is still supported. Although mosquito (Culicidae) wings are of great importance as they play a sex-specific role, little is known about wing sexual dimorphism in these pathogen-vector insects. Detection and characterization of wing sexual dimorphism in culicids may indirectly enhance our knowledge of their epidemiology or reveal sex-linked genes, aspects that have been discussed by vector control initiatives and developers of genetically modified mosquitoes. METHODS: Using geometric morphometrics, we carried out a comparative assessment of wing sexual dimorphism in ten culicid species of medical/veterinary importance from genera Culex, Aedes, Anopheles and Ochlerotatus collected in Brazil. RESULTS: Discriminant analysis revealed significant sexual dimorphism in all the species studied, indicating that phenotypic expression of wing shape in mosquitoes is indeed sex-specific. A cross-validated test performed to reclassify the sexes with and without allometry yielded very similar results. Mahalanobis distances among the ten species showed that the species had different patterns of shape sexual dimorphism and that females are larger than males in some species. CONCLUSION: Wing morphology differed significantly between species. The finding of sexual dimorphism in all the species would suggest that the wing geometry of Culicidae is canalized. Although sexual dimorphism is prevalent, species-specific patterns occur. Allometry was not the main determinant of sexual dimorphism, which suggests that sexual selection or other evolutionary mechanisms underlie wing sexual dimorphism in these insects.