# Ferritin nanoparticle vaccine displaying optimized spike protein confers broad protection against Omicron subvariants

## TL;DR

A new nanoparticle vaccine shows broad protection against Omicron subvariants, including JN.1, by inducing strong immune responses in mice.

## Contribution

A novel ferritin nanoparticle vaccine displaying an optimized spike protein provides broad protection against multiple Omicron subvariants.

## Key findings

- Delta-4S1158 nanoparticles elicited strong IgG, neutralizing antibodies, and Th2-biased T-cell responses in mice.
- JN.1-4S1158 nanoparticles conferred effective protection against Omicron BA.5, XBB, and JN.1 variants.
- Vaccinated mice showed reduced viral loads and no infectious virus in lung and trachea tissues.

## Abstract

The newly emerged Omicron subvariants demonstrate resistance to current therapeutic antibodies and an enhanced ability to evade the vaccine-induced immune responses. Among them, JN.1 sublineages are considered highly immune-evasive, underscoring the urgent need for broadly protective vaccines. Ferritin nanoparticles, with their unique hollow nanocage structure, provide an efficient antigen-display platform for next-generation vaccine development.

Based on the previously constructed Delta-6P-S recombinant protein vaccine with broad-spectrum protective effects, this study optimized the S protein structure displayed on the surface of ferritin nanoparticles by comparing the immune responses induced in C57BL/6J mice.

Delta-4S1158 nanoparticles, containing a truncated S-6P structure with four additional mutation sites, elicited robust S-specific immunoglobulin G (IgG), potent neutralizing antibodies, and a Th2-biased T-cell response in C57BL/6J mice, demonstrating favorable immunogenicity and safety. The JN.1-4S1158 nanoparticles, based on this structural design, induced a strong cross-neutralizing antibody response in C57BL/6J mice and conferred effective protection against Omicron BA.5, XBB, and JN.1 variants. Vaccinated mice exhibited significantly reduced viral genomic loads in trachea and lung tissues compared to controls, with no infectious virus detected. Lung tissue pathology was minimal in vaccinated mice.

The JN.1-4S1158 nanoparticle vaccine demonstrates broad-spectrum protective effects against Omicron subvariants and shows potential for further development. It also provides a basis for the development of a universal SARS-CoV-2 vaccine.