MRNA-1365-RSV

Table of contents

• What is MRNA-1365-RSV?
• How does MRNA-1365-RSV work?
• Which conditions is MRNA-1365-RSV studied for?
• How is MRNA-1365-RSV given?
• What do the clinical trials show?
• What side effects are known?

What is MRNA-1365-RSV?

MRNA-1365-RSV is an investigational messenger RNA (mRNA) vaccine. It is being developed to protect against two respiratory viruses: respiratory syncytial virus (RSV) and human metapneumovirus (hMPV).^[4] The vaccine is not yet authorised as a medicine; it is still in clinical testing. The substance is also referred to in research records as mRNA-1365.^[1]

RSV is the most common cause of chest infection in young children and was associated with over 100,000 child deaths worldwide in 2019.^[4] hMPV caused an estimated 11.1 million chest infections, 502,000 hospital admissions, and 11,300 deaths globally in 2018.^[4] No approved vaccines exist for either virus in young children.^[4]

How does MRNA-1365-RSV work?

MRNA-1365-RSV belongs to the class of RNA vaccines. It works as an immunostimulant: the mRNA instructions prompt the body's own cells to produce a viral protein, which then trains the immune system to recognise and respond to the virus.^[2] Because it targets both RSV and hMPV, the vaccine is designed to help the immune system defend against two different respiratory viruses at once.^[4]

Which conditions is MRNA-1365-RSV studied for?

• Acute lower respiratory infection — the registered trial condition, referring to serious chest infections that can follow RSV or hMPV infection in young children.^[1]
• Respiratory syncytial virus (RSV) infection — a very common virus that infects the lungs and breathing passages and can lead to pneumonia in young children.^[4]
• Human metapneumovirus (hMPV) infection — a common respiratory virus that can cause runny nose, sore throat, cough, fever, headache, and more serious disease such as pneumonia.^[4]

How is MRNA-1365-RSV given?

MRNA-1365-RSV is given as an intramuscular injection, meaning it is injected into a muscle.^[1] In the registered trial, the vaccine was administered alongside comparison injections including a meningococcal vaccine and a placebo (sodium chloride solution 0.9%).^[1] The trial record does not report a specific dose in milligrams, so the exact dose used is not stated in the registry data.^[1]

What do the clinical trials show?

One clinical trial of MRNA-1365-RSV is registered: a Phase 1 study that has been completed.^[1] The trial was randomised, observer-blind, and placebo-controlled, meaning participants were assigned by chance to receive either one of two study vaccines or a placebo, and neither the participants nor the researchers assessing outcomes knew which injection was given.^[4] The study enrolled 690 participants aged 5 months to under 24 months.^[1]

The primary outcomes measured were solicited local and systemic adverse reactions through 7 days after each injection, unsolicited adverse events through 28 days after each injection, medically attended adverse events, adverse events of special interest, serious adverse events, and adverse events leading to discontinuation, all from day 1 to end of study.^[1] These measures focus on safety and tolerability, which is typical for a Phase 1 trial. The study also aimed to assess immunogenicity — how the children's immune systems respond to the vaccines.^[4]

Children taking part were randomly assigned to one of three study injections: mRNA-1345 (an RSV vaccine), mRNA-1365 (the RSV and hMPV vaccine), or a placebo, with an equal chance of receiving each.^[4] Participants were followed for about 24 months.^[4] The trial is completed, but the registry record does not yet report efficacy results; the primary focus of the registered outcomes was safety.^[1]

A related non-interventional study of mRESVIA, an authorised RSV mRNA vaccine from the same developer, is ongoing in the United States to assess effectiveness against serious RSV-related endpoints.^[3] That study is separate from the MRNA-1365-RSV trial and does not involve the investigational RSV/hMPV vaccine.^[3]

What side effects are known?

The registered Phase 1 trial measured solicited local and systemic adverse reactions, such as reactions at the injection site and general symptoms like fever, through 7 days after each injection, as well as unsolicited adverse events and serious adverse events.^[1] Because the trial is completed but detailed safety results are not reported in the registry record, specific side effects of MRNA-1365-RSV cannot yet be listed from these sources.^[1] A published study of a related mRNA-based RSV vaccine in seropositive children aged 12 to 59 months reports on safety and immunogenicity, but the specific side-effect profile of MRNA-1365-RSV is not detailed in the available sources.^[5]