In short
MRNA encoding human cytomegalovirus UL128 is an investigational messenger RNA (mRNA) vaccine component studied for the prevention of cytomegalovirus (CMV) infection. It forms part of the mRNA-1647 vaccine candidate, which completed a Phase 3 trial in 7,484 healthy participants aged 16 to 40 years. The trial evaluated whether the vaccine could prevent primary CMV infection in people who had never been exposed to the virus.
Key points
- MRNA encoding human cytomegalovirus UL128 is an investigational vaccine component studied for preventing cytomegalovirus (CMV) infection.
- The Phase 3 trial enrolled 7,484 healthy participants aged 16 to 40 years.
- The trial compared the mRNA-1647 vaccine against a placebo (sodium chloride 0.9% solution).
- The primary goal was to measure primary CMV infection through seroconversion starting 28 days after the third injection.
- The trial status is completed.
- The vaccine was given as a 3-dose intramuscular injection schedule.
What is mRNA encoding human cytomegalovirus UL128?
MRNA encoding human cytomegalovirus UL128 is an investigational messenger RNA (mRNA) vaccine component. It is one of several mRNA sequences included in the mRNA-1647 vaccine candidate, which is designed to protect against cytomegalovirus (CMV) infection. The substance is not an authorised medicine and remains under investigation in clinical trials.
The UL128 protein is a component of a viral protein complex that cytomegalovirus uses during entry into certain cell types, including endothelial cells that line blood vessels. By encoding this protein in mRNA form, the vaccine aims to teach the immune system to recognise and respond to the virus.
How does mRNA encoding human cytomegalovirus UL128 work?
The UL128 protein, together with related viral proteins UL130 and UL131, forms a complex that promotes a conformational change in the viral glycoprotein gB and enables interaction between gB and gH-gL during entry into endothelial cells. This means the UL128-containing complex helps the virus fuse with and enter cells that line blood vessels.
As an mRNA vaccine component, the mRNA encoding UL128 carries instructions for human cells to temporarily produce the UL128 protein. The immune system can then learn to recognise this viral protein and build a defence against CMV before a natural infection occurs. The vaccine candidate mRNA-1647 combines this component with other CMV protein sequences to broaden the immune response.
Which conditions is it used or studied for?
- Cytomegalovirus infection (CMV) — a common viral infection caused by cytomegalovirus. The trial focused on preventing primary CMV infection in people who had never been exposed to the virus, because a first infection during pregnancy can be passed to the unborn baby and cause health problems.
How is mRNA encoding human cytomegalovirus UL128 given?
In the Phase 3 trial, the mRNA-1647 vaccine containing mRNA encoding human cytomegalovirus UL128 was given as an intramuscular injection at a dose of 100 micrograms. The vaccine was administered on a 3-dose injection schedule. Participants in the comparison arm received sodium chloride 0.9% solution for injection, which served as a placebo.
What do the clinical trials show?
One completed Phase 3 trial evaluated the mRNA-1647 vaccine in 7,484 healthy participants aged 16 to 40 years. The trial had two main goals: to demonstrate whether the vaccine could prevent primary CMV infection in CMV-seronegative female participants, and to evaluate the safety and reactogenicity of the vaccine when given on a 3-dose schedule in all participants.
The primary measure of efficacy was primary CMV infection, defined as seroconversion from a negative to a positive result for serum IgG. Seroconversion means the body has begun producing antibodies against the virus, indicating a new infection. This was assessed starting 28 days after the third injection using a laboratory test based on four CMV antigens that are not encoded by mRNA-1647, so the test could distinguish a natural infection from a vaccine response.
The trial also measured safety outcomes, including 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 the time of consent through end of study. The trial is now completed; results are not detailed in the registry record.