Avaliação de plataformas vacinais experimentais contra o Zika virus utilizando nanopartículas de albumina sérica bovina

Abstract

Zika virus (ZIKV) is an emerging Flavivirus that has caused epidemic outbreaks in islands in the Pacific region and several countries of the Americas. In parallel, severe manifestations such as microcephaly and Guillain-Barré syndrome have increased in incidence during the ZIKV outbreak. This scenario contributed to the establishment of a state of emergency by the World Health Organization (WHO). Therefore, finding an effective vaccine to prevent ZIKV infections is a priority, since there are no vaccines for ZIKV in advanced stages of development. This strengthens the need to test alternative vaccine platforms to prevent ZIKV infections. Preliminary studies from our group have been showed that bovine serum albumin nanoparticles are promising systems for delivery microbial antigens. Therefore, due to the lack of available vaccines for ZIKV and results previously obtained by our group, this study aims to evaluate if bovine serum albumin nanoparticles (BSA-NPs) associated to inactivated ZIKV are able to induce the production of specific antibodies against the virus. In vitro assays were performed to evaluate the cytotoxicity of the formulation and also to evaluate the uptake rate of nanoparticles by permissive cells. Finally, mice were immunized with the nanoparticles containing encapsulated ZIKV (NPZ) or immunized with BSA-NPs mixed with inactivated ZIKV (NP+ZIKV). Anti-ZIKV IgG antibodies were measured in the blood of immunized animals by ELISA. The results indicate that NPZ nanometer platform has 226.1 ± 3.4 nm in diameter and -15.9 ± 1.0 mV of surface charge. Electron Scanning Microscopy indicates that this nanoparticle has an irregular spherical morphology. Detection of the viral genome in nanoparticles suggests the presence of ZIKV in the formulation and a high percentage of encapsulation efficiency (96%). The nanoparticles are uptaken by VERO cells, without any significant cytotoxicity. Mice immunized with nanoparticles containing encapsulated ZIKV (NPZ) did not show substantial output of total IgG antibodies against ZIKV. In contrast, mice immunized with inactivated ZIKV mixed with BSA nanoparticles (NP+ZIKV) showed a significant production of anti-ZIKV antibodies (Total IgG and IgG1). The data strengths the adjuvant potential of BSA-NPs in the elaboration of an effective vaccine against ZIKV. However, Future studies should be performed to determine whether the produced antibodies have neutralizing action and if these antibodies can protect susceptible animals to ZIKV infection