In short
MRNA encoding human cytomegalovirus glycoprotein B is an investigational vaccine being studied to prevent cytomegalovirus (CMV) infection. It is an mRNA-based vaccine designed to teach the immune system to recognise a key protein on the surface of CMV. The most advanced clinical trial completed so far is a Phase 3 study involving 7,484 healthy participants aged 16 to 40 years, which tested whether the vaccine could prevent primary CMV infection in women who had never been exposed to the virus.
Key points
- mRNA-1647 is an investigational vaccine that encodes human cytomegalovirus glycoprotein B.
- The vaccine was tested in a Phase 3 clinical trial with 7,484 healthy participants aged 16 to 40 years.
- The trial focused on preventing primary CMV infection in CMV-seronegative female participants.
- The vaccine was given as a 3-dose intramuscular injection schedule.
- The trial status is Completed, with results measuring seroconversion and safety outcomes.
What is mRNA encoding human cytomegalovirus glycoprotein B?
MRNA encoding human cytomegalovirus glycoprotein B, also known as mRNA-1647, is an investigational vaccine. It is a messenger RNA (mRNA)-based vaccine, which means it delivers genetic instructions to the body's cells to produce a specific viral protein. In this case, the protein is glycoprotein B, a structure found on the surface of human cytomegalovirus (HCMV). Glycoprotein B is essential for the virus to enter human cells and is a key target for neutralising antibodies.
The vaccine is not yet authorised as a medicine and remains under investigation in clinical trials.
How does mRNA encoding human cytomegalovirus glycoprotein B work?
The vaccine works by instructing cells to make the cytomegalovirus glycoprotein B protein. The immune system then recognises this protein as foreign and produces antibodies against it. These antibodies can neutralise the virus, meaning they can block it from infecting cells. Research on the structure of glycoprotein B has shown that it changes shape before and after the virus fuses with a cell, and neutralising antibodies bind to specific parts of this protein. By generating an immune response against glycoprotein B, the vaccine aims to protect against primary CMV infection.
Which conditions is it used or studied for?
- Cytomegalovirus infection (CMV) – a common viral infection caused by human cytomegalovirus that can cause serious complications in newborns when acquired during pregnancy and in people with weakened immune systems.
How is mRNA encoding human cytomegalovirus glycoprotein B given?
In the clinical trial, the vaccine was given as an intramuscular injection. The study used a dose of 100 micrograms administered on a 3-dose injection schedule. A placebo arm in the trial received sodium chloride 0.9% solution for injection, also given intramuscularly.
What do the clinical trials show?
One completed Phase 3 clinical trial evaluated the efficacy, safety, and immunogenicity of mRNA-1647 in healthy participants aged 16 to 40 years. The trial enrolled 7,484 participants and was designed to demonstrate whether the vaccine could prevent primary CMV infection in CMV-seronegative female participants. It also evaluated the safety and reactogenicity of the vaccine when given on a 3-dose injection schedule in all participants.
The primary outcomes measured were primary CMV infection, defined as seroconversion from a negative to a positive result for serum IgG against at least one of four recombinant CMV antigens not encoded by mRNA-1647, assessed starting 28 days after the third injection. Safety outcomes included solicited adverse reactions through 7 days after each injection, unsolicited adverse events through 28 days after each injection, medically attended adverse events from Day 1 through 6 months after the last injection, adverse events of special interest from Day 1 through end of study, and serious adverse events from time of consent through end of study.
Who can take part in these trials?
The completed Phase 3 trial enrolled healthy participants between 16 and 40 years of age. The efficacy analysis focused on CMV-seronegative female participants, meaning women who had not previously been infected with cytomegalovirus and therefore had no antibodies against the virus at the start of the study.