Safety and Immunogenicity of Omicron Variant-Matched Vaccine Booster in Adults

Summary

Under protocol versions 1.01-1.06: The five recently emerged SARS-CoV2 variants that were designated as VOCs are the Alpha variant, Beta variant, Gamma variant, Delta variant and the Omicron variant. The current dominant Omicron variant was designated a VOC by WHO on Nov 26, 2021, and was found to comprise 85% of reported variants in late January 2022. Studies have shown that the prevalent Omicron mutations in the S1 subunit RBD region and NTD region could dramatically change the antigenic features of the viral spike, leading to significantly reduced neutralization Omicron harbors 30 signature mutations (\>50% prevalence) of which 15 are in the S1 subunit RBD region and 8 are in the S1 subunit NTD region. Omicron is a highly contagious variant with threatening immune evasion capabilities even despite robust immune response. Initial modeling showed the Omicron variant being 2.8 times more infectious than the Delta variant. While current vaccines are losing protection against Omicron with respect to infection and mild disease, there is still considerable protection from hospitalisation and severe COVID-19, especially after a booster dose. The International Coalition of Medicines Regulatory Authorities (ICMRA) COVID-19 Omicron Variant Workshop encouraged the international scientific community and vaccine developers to look at alternative approaches to monovalent vaccines. In ICMRA's view, companies should also explore the feasibility of developing bivalent or multivalent variant vaccines to determine if they offer advantages to monovalent vaccines. As advised by ICMRA, the investigated vaccine, mRNA-1273.214 is a bivalent vaccine containing the ancestral SARS-CoV-2 and the Omicron variant spike sequences that will be evaluated as a heterologous boost.

Under protocol version 1.07:The study will also investigate the safety, reactogenicity and immune response of the mRNA-1273.222 administered as a boost vaccine after primary series vaccination comprising 3 doses of an mRNA vaccine .

This study hypothesizes that the peak level of antibodies against SARS CoV-2, will be at two weeks after the first study dose is administered, which is similar to other recent findings (Anderson et al., 2022).2.2.1. The bivalent mRNA-1273.222 vaccine contains mRNA encoding for the spike protein of BA.4/BA.5 as well as mRNA encoding for the original (ancestral Wuhan-Hu-1) strain of the SARS-CoV-2 virus.

Conditions

• COVID-19 Pandemic
• Immunogenicity
• SARS CoV 2 Infection
• COVID-19

Interventions

BIOLOGICAL

mRNA-1273.214 Vaccine

Omicron Variant-Matched Vaccine

BIOLOGICAL

MRNA-1273 Vaccine

Moderna's commercial COVID-19 Vaccine

BIOLOGICAL

Placebo

Normal Saline for injection

BIOLOGICAL

MRNA-1273.222 Vaccine

Moderna's commercial COVID-19 Vaccine

Sponsors & Collaborators

• ModernaTX, Inc.

  collaborator INDUSTRY

• Sheba Medical Center

  lead OTHER_GOV

Principal Investigators

• Gili Regev-Yochay, MD · Sheba Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Model

SEQUENTIAL

Eligibility

Min Age

21 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-09-05

Primary Completion

2024-01-31

Completion

2024-01-31

Countries

• Israel

Study Locations