Efeito adjuvante de nanopartículas de albumina sérica bovina contendo Poli (I:C) em camundongos imunizados com o domínio III da proteína do envelope do Zika virus

Abstract

Zika virus (ZIKV) is considered an emerging Flavivirus associated with epidemics on islands in the Pacific Ocean region and in several countries in the Americas. Severe manifestations such as congenital Zika syndrome and Guillain-Barré syndrome had their incidence increased during these outbreaks and contributed to the establishment of a state of emergency by the World Health Organization (WHO). Since then, the development of an effective vaccine to prevent infections caused by ZIKV has become a priority, since there are few vaccines for ZIKV in advanced stages of development, increasing the need to test alternative platforms. Nanoparticles (NPs) are particulate materials that have sizes ranging from 10 to 1000 nm. NPs are colloidal systems formed by complex structures, which have the potential to prevent enzymatic degradation of the drug or antigen of interest and thus prolong exposure to the active ingredient through controlled release. Polymeric NPs are being widely explored as new vaccine platforms due to the ability of these NPs to stimulate the immune system, thus providing the controlled release of the antigen after its administration. Albumin is a natural, biocompatible, biodegradable, non-toxic polymer and, due to these characteristics, NPs made from bovine serum albumin (NPs-BSA) are promising drug or antigen delivery systems. Therefore, this work aimed to evaluate whether the formulation prepared from nanoparticles composed of bovine serum albumin and polyinosinic-polycytidyl acid (NPPI) when added to a solution containing domain III of the ZIKV envelope protein (zEDIII) are capable of inducing neutralizing antibodies. For this, female mice were immunized subcutaneously with nanoparticles containing polyinosinic-polycytidyl acid (NPPI) with or without addition of domain III of the ZIKV envelope protein (zEDIII) on days 0, 7 and 14. -zEDIII were evaluated by ELISA. Sera from previously immunized animals were passively transferred to one-day-old neonate mice after one hour of ZIKV infection. The neonates were followed up and evaluated for weight, clinical and neurological signs for 28 days or until the day of their death. The brains of these animals were collected for viral load quantification assays. The results showed that NPPI+zEDIII immunized mice produced significant titers of anti-zEDIII IgG antibodies. This immunization was also able to induce the production of neutralizing antibodies, capable of potentially neutralizing ZIKV infection in vitro. Furthermore, the serum of animals immunized with NPPI+zEDIII was able to prevent clinical and neurological signs in a model of passive transfer of antibodies to neonatal animals, in addition to reducing viral load, expression of pro-inflammatory cytokines and inflammation in the brain of these animals. Therefore, our results show that NPPI+zEDIII is a promising vaccine candidate to fight infections caused by ZIKV.