The phase 2, randomized, placebo-controlled, dose-finding trial evaluated the mRNA-based cytomegalovirus vaccine, which features a lipid nanoparticle formulation.
An mRNA-based vaccine candidate to prevent cytomegalovirus (CMV) demonstrated immunogenicity and was generally well-tolerated in results of a phase 2 trial (NCT04232280) presented as a poster at IDWeek 2022, held October 19-23, 2022, in Washington, DC.
Preventing CMV infection in a safe and effective way represents an urgent unmet need, as the congenital virus infection can contribute to severe long-term health consequences when left untreated. Leveraging mRNA technology, investigators developed mRNA-1647, a vaccine that features a lipid nanoparticle formulation comprising 6 mRNA sequences encoding for 2 CMV antigens (glycoprotein B and the pentameric glycoprotein complex).
The phase 2, randomized, placebo-controlled, observer-blind trial sought to evaluate the safety and immunogenicity of 3 different doses of mRNA-1647 (50, 100, or 150 µg) among healthy adults between the ages of 18 and 40 years. Investigators divided the trial into 2 parts. Part 1 involved randomizing CMV-seronegative and CMV-seropositive men and women 3:1 to either mRNA-1647 or placebo administered at months 0, 2, and 6. The middle dose of 100 µg was selected as the focus for Part 2, which randomized CMV-seronegative and CMV-seropositive women 3:1 to either mRNA-1647 100 µg or placebo at months 0, 2, and 6.
Investigators monitored the following safety end points through 7 days, 28 days, and 6 months post-vaccination: solicited local and systemic adverse reactions, unsolicited adverse events (AEs), and medically attended AEs, as well as serious AEs throughout the study period. Immunogenicity was measured via antigen-specific antibody titers and neutralizing antibody titers against epithelial cell infection and against fibroblast infection.
A total of 252 and 63 participants were randomized in Parts 1 and 2, respectively. mRNA-1647 100 µg induced robust antibody responses in CMV-seronegative participants, boosted antibody titers in CMV-seropositive participants, and was generally well-tolerated, according to an interim analysis, which included Part 1 through 1 month after Dose 3.
Investigators reported no notable differences in the safety profile when compared with an additional interim analysis of Part 1 through the end of the study and Part 2 through 1 month after Dose 3. The most commonly reported solicited local adverse reaction among participants who received mRNA-1647 was injection site pain, while headache, fatigue, myalgia, arthralgia, and chills were the most commonly reported systemic solicited adverse reactions.
“Treatment-related unsolicited AEs were reported by 30 (19%) CMV seronegative and 10 (14%) CMV-seropositive mRNA-1647 recipients, and in 6 (11%) CMV-seronegative and 3 (11%) CMV-seropositive placebo recipients,” investigators reported. “Unsolicited [medically attended adverse events] were reported by 31 (19%) CMV-seronegative and 11 (15%) CMV-seropositive mRNA-1647 recipients, and in 10 (19%) CMV-seronegative and 6 (22%) CMV-seropositive placebo recipients.”
A total of 6 (3%) individuals had to discontinue the study vaccine because of an unsolicited treatment-emergent AE. Four of the 6 experienced treatment-emergent AEs considered to be treatment-related. No deaths were reported.
Data regarding immunogenicity is still being generated, the research team reported. However, initial data suggests strong immune response among CMV-seronegative and CMV-seropositive participants. In CMV-seronegative individuals who received mRNA-1647, geometric mean titers (GMTs) of serum neutralizing antibodies (nAbs) against epithelial cell infection increased above baseline after dose 1 and continued to increase after doses 2 and 3.
“nAb GMTs exceeded the CMV-seropositive baseline GMT benchmark in all treatment groups after doses 2 and 3, and remained above the benchmark at Months 12 and 18,” investigators reported.
Among CMV-seropositive participants in the mRNA-1647 treatment group, nAB GMTs against epithelial cell infection also increased after dose 1 and were comparable or exceeded that level after dose 2 and 3.
“Available data from this Phase 2 trial suggest that mRNA-1647 100 µg was immunogenic in CMV-seronegative and CMV-seropositive participants and was generally well-tolerated,” investigators concluded. “The mRNA-1647 candidate vaccine is being evaluated in a Phase 3 trial.”