Safety and Immunogenicity of a Messenger RNA-Based Cytomegalovirus Vaccine in Healthy Adults: Results From a Phase 1 Randomized Clinical Trial.

ABSTRACT

BACKGROUND: This phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1647, a messenger RNA (mRNA)-based cytomegalovirus (CMV) vaccine, in CMV-seronegative and -seropositive adults. METHODS: Participants were randomly assigned to receive 30, 90, 180, or 300 µg of mRNA-1647 or placebo on a 0-, 2-, and 6-month schedule and followed for 12 months after the last dose. RESULTS: A total of 154 (80 CMV-seronegative and 74 CMV-seropositive) participants were enrolled; 118 participants were randomized to mRNA-1647 and 36 to placebo. Mean (standard deviation) age was 32.5 (8.6) and 35.1 (8.9) years in the placebo and mRNA-1647 groups, respectively, in phase B (63% and 64% female) and 42.5 (6.2) and 33.3 (8.7) years, respectively, in phase C (2% and 16% female). No deaths, related serious adverse events, or adverse events of special interest were reported. Most adverse reactions were grade ≤2 severity. Increased neutralizing antibody, binding antibody, and antigen-specific cell-mediated responses were observed across mRNA-1647 treatment groups, regardless of CMV serostatus. CONCLUSIONS: This phase 1, first-in-human trial demonstrated that mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses. Clinical Trials Registration. NCT03382405.

Cytomegalovirus (CMV) is a common virus that can cause severe illness in people with weakened immune systems and in babies infected from a mother with a CMV infection during pregnancy. To date, there is no approved vaccine available to prevent CMV infection. This study in healthy adult participants is the first to test an investigational CMV vaccine called mRNA-1647, a messenger RNA (mRNA)-based vaccine developed using a technology similar to that used for vaccines to prevent COVID-19. Here, we evaluated the safety of mRNA-1647 and whether mRNA-1647 can increase levels of antibodies and immune cells (parts of the immune system that help defend against a foreign invader such as a virus). Most of the side effects observed after mRNA-1647 injection were mild; these included common reactions that occur after vaccination such as pain at the site of vaccination, headache, tiredness, muscle aches and pains, and chills. Levels of antibodies and immune cells in the blood increased after vaccination with mRNA-1647. Together, these findings show that mRNA-1647 was well tolerated and produced an immune response in adults, and support continued research on mRNA-1647 as a potential approach to prevent CMV infection.