# Phase 1 Randomized Controlled Trial of the Safety and Immunogenicity of the SARS-CoV-2 (Omicron BA.5) mRNA-CR-04 Vaccine in Adults 18–49 Years of Age

## TL;DR

A new mRNA vaccine targeting the Omicron BA.5 variant of SARS-CoV-2 was tested in adults, showing it is safe and triggers strong immune responses.

## Contribution

The study introduces a novel mRNA vaccine platform using the BA.5 Spike protein and demonstrates its safety and immunogenicity in humans.

## Key findings

- The mRNA-CR-04 vaccine was well tolerated with mostly mild to moderate side effects.
- All tested doses induced strong neutralizing antibody responses against the BA.5 variant and the wild-type SARS-CoV-2.
- Immune responses remained detectable for at least 6 months post-vaccination.

## Abstract

This study (NCT05972993) evaluated a novel mRNA vaccine construct using the SARS-CoV-2 BA.5 Spike (S) protein as the model antigen (mRNA-CR-04).

This first-in-human Phase 1, randomized, placebo-controlled trial enrolled 72 participants in Part A (sentinel vaccination and dose escalation) and 42 in Part B (dose exploration). Adult participants 18–49 years of age were randomized in 3 groups to receive one dose of mRNA-CR-04 (either 10, 30, or 100 µg) or placebo (3:1) in Part A, and 3 µg, 10 µg, or placebo (3:3:1) in Part B. Vaccine safety and immunogenicity in terms of neutralizing titers were assessed until 6 months postinvestigational product administration.

Solicited adverse events (AEs) were mostly mild to moderate and transient. In Part A, Grade 3 reactogenicity was only observed in the 100 µg group (n = 3, 16.7%), and Grade 3 nonsolicited AEs only occurred as causally unrelated serious AEs in 2 participants. No safety concerns deemed causally related to mRNA-CR-04 were raised on review of clinical safety data and clinical laboratory test results. All doses elicited notable neutralizing titers against the vaccine-encoded SARS-CoV-2 BA.5 variant and induced cross-neutralizing titers against the wild type (D614G) variant. The magnitude of the immune response tended to increase with dose. Neutralizing titers waned by Month 6 but remained above baseline levels.

The investigational mRNA-CR-04 vaccine was generally well tolerated, and all doses induced a robust immune response against the encoded antigen at doses ranging between 3 and 100 µg. Further investigation of potential vaccine candidates using this novel mRNA platform is warranted.

As anticipated, the investigational mRNA-CR-04 vaccine elicited robust immune responses against the encoded antigen in adults that persisted for at least 6 months. No safety concerns deemed causally related to mRNA-CR-04 were observed for doses between 3 and100 µg.