mRNA-1647 vaccine well tolerated regardless of CMV serostatus

MRNA-1647, Moderna's investigational mRNA-based vaccine against cytomegalovirus (CMV), is well tolerated in healthy adults regardless of CMV serostatus, according to a study presented at IDWeek 2023.

“CMV is the leading infectious cause of birth defects globally and a substantial cause of morbidity in immunocompromised individuals. Currently, there is no approved vaccine against CMV,” said Dr Sandeep Basnet from Moderna, Inc., in Cambridge, Massachusetts, US, who presented the study.

This phase II, observer-blind, placebo-controlled, dose-finding trial analysed 315 healthy CMV-seronegative and -seropositive adults (aged 18–40 years) to assess the safety and immunogenicity of mRNA-1647. During the first part of the study, all participants were randomized in a 3:1 ratio to receive either mRNA-1647 (50, 100, or 150 μg) or placebo at 0, 2, and 6 months. As for the second part of the study, only females were randomized to receive mRNA-1647 100 μg or placebo at 0, 2, and 6 months. [IDWeek 2023, abstract 2892]

Among CMV-seronegative participants, the rates of solicited adverse reactions (ARs) were 84.4 percent (50 µg), 87.5 percent (100 µg), and 91.1 percent (150 µg) after the first dose of mRNA-1647. For CMV-seropositive adults, the rates were 94.4, 94.6, and 94.4 percent for the three respective doses. However, most ARs were of grade 1 or 2 in severity, and there was no significant difference between the serostatus groups.

After dose 1, the most commonly reported local and systemic solicited ARs across the serostatus groups were pain (73.3–89.2 percent [mRNA-1647] and 18.5–18.9 percent [placebo]) and fatigue (28.9–72.2 percent [mRNA-1647] and 25.9–30.2 percent [placebo]), respectively.

Similar trends in ARs were also observed after doses 2 and 3, according to the researchers.

The overall rates of treatment-emergent adverse events (AEs) were comparable between the mRNA-1647 and placebo groups in both CMV-seronegative and -seropositive participants (20.4 percent and 16.4 percent, respectively).

There were no deaths, serious AEs related to vaccination, or unsolicited AEs leading to treatment discontinuation reported in either treatment group.

With regard to antibody-mediated immunogenicity by CMV serostatus, neutralizing antibodies (nAbs) against epithelial cell and fibroblast infections increased following the administration of mRNA-1647 across doses 1, 2, and 3 among the CMV-seronegative participants.

“Of note, nAbs exceeded the CMV-seropositive benchmark after doses 2 and 3 and remained above the benchmark through month 18,” Basnet noted.

Similarly, among the CMV-seropositive participants, nAbs against epithelial cell and fibroblast infections increased after dose 1 of mRNA-1647.

“[Overall, vaccination with] mRNA-1647 was generally safe and well-tolerated and induced antigen-specific immune responses at all dose levels in both CMV-seronegative and -seropositive participants,” said Basnet.

“Results from this study supported selection of the mRNA-1647 100-µg dose level for the ongoing phase III trial,” he added.