mRNA-1647 Vaccine Description

Moderna’s mRNA-1647 vaccine candidate the first mRNA vaccine for an infectious disease to enter a Phase 2 study.

The mRNA-1647 vaccine candidate combining 6 mRNAs in a single vial, which encodes for two antigens on the surface of CMV. About .5% of infants are born with congenital cytomegalovirus (CMV) infection. Around 20% of babies born with congenital CMV infection will have long-term health problems. A pregnant woman can pass CMV to her fetus following primary infection, reinfection with a different CMV strain, or reactivation of a previous infection during pregnancy. The risk of transmission for primary infection is 30 to 40% in the first and second trimesters and 40 to 70% in the third trimester.

The risk of transmission following non-primary infection is much lower (3%). The risk of complications to the fetus is greatest if a primary infection occurs during the first trimester.

The Institute of Medicine (now National Academy of Medicine) designated CMV as a “highest priority” category for vaccine development in 1999.

Moderna’s mRNA vaccine technology offers potential advantages in efficacy, speed of development, and production scalability and reliability, which may position our company as a leader in preparing for and responding to infectious disease threats.

mRNA-1647 Vaccine Indication

mRNA-1647 comprises six mRNAs encoding two antigens in one vaccine and is designed to protect against CMV infection. Of the six mRNAs, five encode the subunits of the CMV pentamer complex and one mRNA encodes the glycoprotein B (gB) protein, both of which are highly immunogenic.

The pentamer complex is important for CMV entry into a variety of cells, including epithelial cells, while gB is important for entry into all susceptible cells including fibroblasts. A vaccine that produces an immune response against both pentamer and gB has the potential to prevent CMV entry into a range of target cell types and thus prevent primary and congenital infections.

Unlike a protein-based vaccine, mRNA-1647 instructs the body’s own cells to manufacture the antigens, resulting in functional antigens that mimic those presented to the immune system by CMV during a natural infection. Preclinical data previously published in Vaccine showed that vaccination with mRNA-1647 in animal models elicited potent and durable neutralizing antibody titers.

mRNA-1647 Vaccine Dosage

Clinical studies are on-going to determine the proper vaccine dosage.

mRNA-1647 Vaccine Updates:

• February 11, 2020 - Moderna announced that the Phase 2 dose-confirmation study of its mRNA vaccine against cytomegalovirus (CMV) is enrolling ahead of plan with data now expected in the third quarter of 2020. 
• January 9, 2020-- Moderna, Inc., announced positive seven-month interim safety and immunogenicity data after the third and final vaccination in the Phase 1 study of its investigational cytomegalovirus (CMV) vaccine (mRNA-1647). The findings build on the previously reported three-month interim analysis, after two vaccinations, announced at the Company’s R&D Day in September 2019. Additionally, the Company announced that the first participant was dosed in a Phase 2 dose-confirmation study.
• September 12, 2019:  Moderna, Inc. is a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, today announced positive data from the three-month interim analysis of safety and immunogenicity of the Phase 1 study of its investigational cytomegalovirus (CMV) vaccine (mRNA-1647). mRNA-1647 is a wholly-owned program in Moderna’s prophylactic vaccine portfolio. Based on these data, Moderna is advancing mRNA-1647 to a dose-confirmation Phase 2 study in the near term. Preparation has also begun for a pivotal Phase 3 study designed to evaluate the efficacy of mRNA-1647 against primary CMV infection. The Phase 2 study will test the intended Phase 3 formulation, which contains the same proprietary lipid nanoparticle (LNP) used in this Phase 1 study.
• February 20, 2018 — Moderna announced the publication of new data in the scientific journal Vaccine that demonstrate the versatility of its mRNA vaccine platform in developing novel prophylactic vaccines to potentially prevent human cytomegalovirus (CMV) infections and associated disease burdens, both for pregnant women and in transplant patients.

Clinical Studies:

• Phase 2 Clinical Trial - This clinical study will assess the safety and immunogenicity of 3 dose levels of mRNA-1647 cytomegalovirus vaccine in CMV-seronegative and CMV-seropositive healthy adults 18-40 years of age.
• Phase 1 Clinical Trial - This clinical study will assess the safety, reactogenicity, and immunogenicity of mRNA-1647 and mRNA-1443 cytomegalovirus vaccines in healthy adults.