Zika Virus Envelope Domain III Recombinant Protein Delivered With Saponin-Based Nanoadjuvant From Quillaja brasiliensis Enhances Anti-Zika Immune Responses, Including Neutralizing Antibodies and Splenocyte Proliferation

Abstract

Nanoadjuvants that combine immunostimulatory properties and delivery systems reportedly bestow major improvements on the efficacy of recombinant, protein-based vaccines. Among these, self-assembled micellar formulations named ISCOMs (immune stimulating complexes) show a great ability to trigger powerful immunological responses against infectious pathogens. Here, a nanoadjuvant preparation, based on saponins from Quillaja brasiliensis, was evaluated together with an experimental Zika virus (ZIKV) vaccine (IQB80-zEDIII) and compared to an equivalent vaccine with alum as the standard adjuvant. The preparations were administered to mice in two doses (on days zero and 14) and immune responses were evaluated on day 28 post-priming. Serum levels of anti-Zika virus IgG, IgG1, IgG2b, IgG2c, IgG3 were significantly increased by the nanoadjuvant vaccine, compared to the mice that received the alum-adjuvanted vaccine or the unadjuvanted vaccine. In addition, a robust production of neutralizing antibodies and in vitro splenocyte proliferative responses were observed in mice immunized with IQB80-zEDIII nanoformulated vaccine. Therefore, the IQB80-zEDIII recombinant preparation seems to be a suitable candidate vaccine for ZIKV. Overall, this study identified saponin-based delivery systems as an adequate adjuvant for recombinant ZIKV vaccines and has important implications for recombinant protein-based vaccine formulations against other flaviviruses and possibly enveloped viruses.

Silk Fibroin-Coated Nano-MOFs Enhance the Thermal Stability and Immunogenicity of HBsAg

“…Splenocyte proliferation is another method used to assess the efficacy of vaccine immunity. Effector lymphocytes are rapidly activated to mount an immune response, and immune memory cells can proliferate rapidly upon restimulation with the same antigen in vitro . As shown in Figure F, the splenocyte proliferation index in the HZ-1, HSZ-1, HZ-2, and HSZ-2 groups before and after heat treatment was significantly higher than those in the PBS, HBsAg, and Alum + HBsAg groups.…”

“…Effector lymphocytes are rapidly activated to mount an immune response, and immune memory cells can proliferate rapidly upon restimulation with the same antigen in vitro. 50 As shown in Figure 7F, the splenocyte proliferation index in the HZ-1, HSZ-1, HZ-2, and HSZ-2 groups before and after heat treatment was significantly higher than those in the PBS, HBsAg, and Alum + HBsAg groups. The above results suggest that these nanoparticles can still produce a positive immunological memory effect even after heat treatment.…”

“…Mouse blood was collected, and the red blood cells were separated by centrifugation (1000 rpm, 10 min), washed three times with PBS, and made into a 2% erythrocyte suspension. Then, 500 μL of different concentrations of HZ and HSZ (25,50,100,200,300,400, and 500 μg/mL) was added to an equivalent volume of 2% erythrocyte suspension, with PBS as the negative control and 0.2% Triton X-100 as the positive control. The various combined solutions were incubated at 37 °C for 1 h. After centrifugation, the samples were photographed, and the supernatant was collected.…”

Vaccination with a Zika virus envelope domain III protein induces neutralizing antibodies and partial protection against Asian genotype in immunocompetent mice

“…The lower IgG2c-to-IgG1 ratio by Z_EDIII administration suggests that the cellular immunity is biased to Th2 response. Adjuvants in ZIKV subunit vaccines support neutralizing antibody production [ 26 ]. This study used two adjuvants, MPLA and Alum.…”

“…Briefly, 100 μl aliquots of diluted serum (1:50,000) were added per well. Z_EDIII-specific antibodies (IgG, IgG1, and IgG2c) Shin et al Tropical Medicine and Health (2022) 50:91 in sera were determined by indirect ELISA as described previously [26,27]. Microplates (Nunc-Immuno Plates; Thermo Scientific, UK) were coated with Z_EDIII (1 μg/ ml) at 4 °C overnight.…”