Estudo pré clínico de candidatos vacinais contra o vírus Zika, utilizando a proteína do envelope viral, recombinante, funcionalizada ou não em nanobastões de ouro

Abstract

Among the several known arboviruses with considerable global spread, the Zika virus (ZIKV) originated on the African continent, spreading to other continents over the years with increasing international travel. Causing mild symptoms, predominantly in tropical countries, the disease continues to emerge silently with worrying consequences. Its connection with Guillain-Barré Syndrome and Congenital Zika Syndrome denotes the seriousness of a neglected disease with no available vaccination coverage. With scientific advances in the development of vaccine technology as a result of the recent SARS-CoV-2 pandemic, new vaccine platforms have been created and old ones have been improved. Among improved technologies, recombinant subunit vaccines plus the use of nanocarriers for antigen delivery and among the highlighted materials, gold nanoparticles, have been studied. With physical-chemical properties that allow it to bind to organic molecules such as proteins, the choice appears promising. In previous work, the research group observed the potential application of nanoparticles in biomedical sciences with positive results, demonstrating the capacity for heterologous expression of a recombinant protein (produced in Escherichia coli, BL21) of the ZIKV viral envelope (ZIKV-E), functionalized in commercial gold nanorods (GNR) to increase its immunogenicity and bioavailability. The work also found that the adjuvant formed by monophosphoryl lipid A (MPLA) combined with 7DW8-5 (a potent analogue of α-GalCer) has a better response induction among the other formulations tested. The main objective of the present work was to evaluate the immune response developed by experimental vaccines in the C57BL/6 model, in addition to the pre-clinical study of the experimental vaccines described in the face of a challenge with ZIKV with previously immunized pregnant female C57BL/6 mice, in order to observe possible changes in the prenatal neurodevelopment of fetuses, verifying vertical transmission as reported in the literature. After immunization of the mice, high levels of anti-ZIKV neutralizing antibodies were detected. Furthermore, experimental vaccines were able to induce the activation of immune system cells in C57BL/6 mice, the activation of memory cells, and a tendency to increase IFN-γ secreted by CD4+ and CD8+ lymphocytes. These results were observed mainly in the group immunized with the complete experimental vaccine. Fetal viability has been shown to be affected in an infection scenario without the vaccine candidate, with a greater number of reabsorptions compared to the number of fetuses that would exist in the offspring in a scenario without the challenge. Still in this data, the immunized and subsequently challenged animals had a significant statistical value compared to the animal that received the saline solution (PBS) or just pure GNR, data similar to the animals in the unchallenged group, suggesting that the experimental vaccines were satisfactorily protective.