Moderna: mRNA encoding monoclonal antibodies against Chikungunya virus

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Moderna: mRNA encoding monoclonal antibodies against Chikungunya virus

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Moderna: mRNA encoding monoclonal antibodies against Chikungunya virus. 

Chikungunya virus (CHIKV) infection can cause acute diseases characterized by fever, rash, and joint pain. The virus is transmitted to humans by Aedes mosquitoes.

At present, there are about 3 million infections worldwide each year, mainly in Africa, Southeast Asia, It is prevalent in the Indian Ocean……

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

In addition, the virus may be fatal to infants or people with weakened immune functions, and there is currently no approved prevention or treatment method for marketing.

Recently, Moderna published a research paper titled: A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus in Nature Medicine , a top international medical journal .

This paper reports the results of a phase 1 clinical trial using lipid nanoparticles ( LNP ) to deliver mRNA (mRNA-1944) of a monoclonal antibody that neutralizes Chikungunya virus (CHIKV) .

This is the first monoclonal antibody that has shown in vivo expression and detectable mRNA encoding in clinical trials 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 the infected person or its specific monoclonal antibodies 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., and neutralizing antibodies for the treatment of COVID-19 pneumonia are also in clinical trials.

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

Therefore, there are researches on the use of DNA or RNA delivery technology for more efficient, safe, and low-cost monoclonal antibody therapies.

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

Protective neutralizing antibodies. This research paved the way for the clinical application of the therapy.

On the basis of the above-mentioned preclinical studies, Moderna conducted a phase 1 clinical trial from January 2019 to June 2020 to confirm the safety, tolerability, pharmacokinetics and pharmacodynamics of the therapy.

A total of 38 people participated in this clinical trial. They were randomly assigned to receive a single intravenous injection of 0.1 mg/Kg, 0.3 mg/Kg, or 0.6 mg/Kg, or two injections of 0.3 mg/Kg, or received a placebo Agent.

At 12, 24, and 48 hours after the 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 continued for 16 More than weeks.

Participants who received two injections of 0.3 mg/Kg and received the second dose one week after the first injection increased their CHKV-24 IgG antibody levels by 1.8 times.

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

This indicates that LNP delivers mRNA and expresses monoclonal antibodies with Great potential for prevention and treatment of diseases.

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 .

In November 2021, Moderna announced a collaboration with the gene editing startup Metagenomi to combine Metagenomi ‘s CRISPR-based next-generation gene editing system and other gene editing systems with Moderna ‘s mRNA technology and LNP delivery technology to develop the next generation in vivo gene therapy editing method is a method for the treatment of patients develop severe genetic diseases.

All these indicate that Moderna has begun to accelerate its deployment in other fields after its great success with the COVID-19 mRNA, and use its mRNA delivery platform for the prevention and treatment of a variety of other diseases, not just confined to infectious diseases.

Reference:
1. https://www.nature.com/articles/s41591-021-01573-6
2. https://www.science.org/doi/10.1126/sciimmunol.aaw6647
3. https://www.abcellera.com/news/abcellera-collaboration-moderna

Moderna: mRNA encoding monoclonal antibodies against Chikungunya virus

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