The first monoclonal antibody encoded by mRNA that can be expressed and detected in vivo in clinical trials

Chikungunya virus (CHIKV) infection can cause acute illnesses characterized by fever, rash, and joint pain

At present, there are about 3 million infections in the world every year, mainly in Africa and Southeast Asia.

As many as 50% of patients infected with Chikungunya virus (CHIKV) will develop severe and chronic arthritis

In addition, this virus can be fatal to infants or people with weakened immune functions, and there are currently no approved prevention or treatment methods for marketing

Recently, Moderna published a research paper entitled "A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus" in the top international medical journal "Natural Medicine"

This article reports the results of a phase I clinical trial using lipid nanoparticles (LNP) to deliver monoclonal antibody mRNA (mRNA-1944) that neutralizes Chikungunya virus (CHIKV)

This is the first monoclonal antibody that has been shown to be expressed and detectable in vivo in a clinical trial and can provide treatment for Chikungunya virus (CHIKV) infection without serious side effects

Chikungunya virus (CHIKV) infection can induce the human body to produce high levels of neutralizing antibodies

The use of convalescent serum from an infected person or its specific monoclonal antibody can prevent animal models from being infected with Chikungunya virus

In recent years, a variety of neutralizing antibodies have been approved for the prevention or treatment of respiratory syncytial virus, Ebola virus, HIV virus, etc.

These neutralizing antibodies face the problems of purification and post-translational modification during the production process

Therefore, there are researches using DNA or RNA delivery technology to treat with more effective, safe, and low-cost monoclonal antibodies

As early as before the COVID-19 outbreak in May 2019, Moderna published a preclinical research paper in the journal Science Immunology [2], using lipid nanoparticles (LNP) to deliver light chain-encoding human monoclonal Antibody (CHKV-24 IgG) and heavy chain mRNA, targeting Chikungunya virus E2 glycoprotein, can protect mice infected with Chikungunya virus from arthritis, musculoskeletal diseases and lethal attacks

Protective neutralizing antibodies

Based on the above-mentioned preclinical studies, Moderna conducted a phase I clinical trial from January 2019 to June 2020 to confirm the safety, weather resistance, pharmacokinetics and pharmacodynamics of the therapy

A total of 38 people participated in this clinical trial

At 12, 24, and 48 hours after a single injection, they were observed to produce CHKV-24 IgG antibodies with neutralizing activity in a dose-dependent manner
.

The antibody production in the 0.
3 mg/Kg and 0.
6 mg/Kg dose groups lasted more than 16 weeks
.

Participants who received two injections of 0.
3 mg/Kg and the second injection one week after the first injection had a 1.
8-fold increase in CHKV-24 IgG antibody levels
.

This clinical trial showed that two independent mRNAs encoding CHKV-24 IgG heavy chain and light chain can produce functional neutralizing antibodies, and the antibody level can last for several months
.

It is suggested that LNP can deliver mRNA and express monoclonal antibodies, which has great potential in disease prevention and treatment
.

In addition, in September 2021, Moderna announced a collaboration with AbCelera, a Canadian antibody drug discovery star company, to jointly develop mRNA-encoded antibody therapies
.