# Safety, immunogenicity, and optimal dosing of VLPCOV-02, a SARS-CoV-2 saRNA vaccine with modified 5-methylcytosine base

## TL;DR

This study evaluates a modified SARS-CoV-2 RNA vaccine, finding it safe and effective at inducing strong immune responses.

## Contribution

The study demonstrates that incorporating 5-methylcytosine improves vaccine safety without reducing immunogenicity.

## Key findings

- VLPCOV-02 induced strong neutralizing antibodies lasting up to 52 weeks.
- A 3 μg dose of VLPCOV-02 provided immunity comparable to a 30 μg dose of Comirnaty.
- The vaccine induced robust CD4+ and CD8+ T cell responses in both young and elderly participants.

## Abstract

Variant-adapted vaccines are becoming increasingly important for continued COVID-19 prevention. Part 1 of the phase 1/2 study with VLPCOV-02, a lipid nanoparticle-encapsulated, self-amplifying RNA (saRNA) vaccine with a modified 5-methylcytosine (5 mC) base, demonstrated lower reactogenicity and incidence of adverse events, and induction of antibody responses. We report results of part 2 with an expanded number of participants (N = 323 [3 μg VLPCOV-02: 53 non-elderly and 54 elderly; 7.5 μg VLPCOV-02: 55 non-elderly and 55 elderly; 30 μg Comirnaty ready to use: 52 non-elderly and 54 elderly]) to determine the optimal dose level. VLPCOV-02 induced robust immunoglobulin G titers against receptor-binding domain and neutralizing antibody titers against all variants of SARS-CoV-2 tested, and induced CD4+ and CD8+ T cell responses. These results indicate that the incorporation of a modified 5 mC base improves the safety profile of the saRNA vaccine without compromising immunogenicity, supporting further development of this platform as a booster vaccine.

•5 mC-incorporated VLPCOV-02 improved safety without compromising immunogenicity•VLPCOV-02 induced strong, durable neutralizing antibodies up to 52 weeks•An optimal dose of 3 μg VLPCOV-02 achieved immunity comparable to 30 μg BNT162b2•VLPCOV-02 induced robust CD4+ Th1 and CD8+ T cell responses across age groups

5 mC-incorporated VLPCOV-02 improved safety without compromising immunogenicity

VLPCOV-02 induced strong, durable neutralizing antibodies up to 52 weeks

An optimal dose of 3 μg VLPCOV-02 achieved immunity comparable to 30 μg BNT162b2

VLPCOV-02 induced robust CD4+ Th1 and CD8+ T cell responses across age groups

Immunology