# Flavivirus-based bivalent nanoparticle vaccines induce neutralizing antibodies and Th1 responses against flavivirus and coupling antigens

## TL;DR

Researchers created a bivalent vaccine using flavivirus nanoparticles that can trigger immune responses against both JEV and SARS-CoV-2.

## Contribution

A novel bivalent nanoparticle vaccine platform using flavivirus-like particles to induce Th1 responses and neutralizing antibodies against multiple pathogens.

## Key findings

- Mice immunized with coupled nanoparticles produced high neutralizing antibodies against JEV and SARS-CoV-2.
- The vaccine induced Th1 immune responses with increased IFN-γ-producing cells and IgG2a production.
- JEV nanoparticles coupled with parvovirus B19 RBD also induced neutralizing antibodies against both JEV and parvovirus.

## Abstract

Effective vaccines against flaviviruses, including Japanese encephalitis virus (JEV), are widely used. We developed antigen-loaded nanoparticle vaccines, using JEV virus-like particles (JEV-VLPs) as carriers. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (S-RBD) was covalently coupled to specific peptide insertion sites on the JEV envelope protein. Mice immunized with these coupled particles (JEprME-S-RBD) produced high levels of neutralizing antibodies against both JEV and SARS-CoV-2, with broad activity against multiple SARS-CoV-2 variants. These mice also had a larger number of interferon (IFN)-γ-producing cells with higher levels of anti-S-RBD IgG2a production than mice receiving the JEV-VLP and S-RBD without coupling. These results suggested the induction of T helper (Th) 1 immune responses. We also constructed JEV nanoparticles coupled with human parvovirus B19 RBD, which efficiently induced neutralizing antibodies against both JEV and parvovirus. Therefore, flaviviral nanoparticles can serve as versatile multivalent vaccine platforms by incorporating neutralizing epitopes from different pathogens.

•JEV nanoparticles were coupled to the SARS-CoV-2 S-RBD antigen•Immunization with nanoparticles induced neutralizing antibodies against both antigens•Immunization with nanoparticles also induced Th1 immune responses•JEV nanoparticles have potential as carriers for multivalent vaccines

JEV nanoparticles were coupled to the SARS-CoV-2 S-RBD antigen

Immunization with nanoparticles induced neutralizing antibodies against both antigens

Immunization with nanoparticles also induced Th1 immune responses

JEV nanoparticles have potential as carriers for multivalent vaccines

Natural sciences; Biological sciences; Immunology