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Cytomegalovirus (CMV) is a leading cause of congenital infections and significant health complications in immunocompromised individuals. With no licensed CMV vaccine available, the development of the mRNA-1647 offers promising advancements in CMV prevention. We have reviewed results from Phase 1 and 2 clinical trials of the mRNA-1647 vaccine, demonstrating robust immune responses in both seronegative and seropositive participants. Vaccines exhibited significantly elevated neutralizing antibody titers against CMV, particularly in fibroblast and epithelial cells, with sustained responses lasting up to 18 months post-vaccination. The mRNA-1647 vaccine triggered strong T-cell and memory B-cell responses, suggesting its potential for long-term protection against CMV infection. The ongoing Phase 3 CMVictory trial evaluates the safety and immunogenicity of mRNA-1647 in women of childbearing age, with preliminary data showing promise in preventing congenital CMV transmission. This vaccine could significantly reduce CMV-related morbidity and mortality, particularly in newborns and immunocompromised individuals, addressing a critical unmet medical need.

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http://dx.doi.org/10.1080/21645515.2025.2450045DOI Listing

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Cytomegalovirus (CMV) is a leading cause of congenital infections and significant health complications in immunocompromised individuals. With no licensed CMV vaccine available, the development of the mRNA-1647 offers promising advancements in CMV prevention. We have reviewed results from Phase 1 and 2 clinical trials of the mRNA-1647 vaccine, demonstrating robust immune responses in both seronegative and seropositive participants.

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Article Synopsis
  • mRNA-1647 is an experimental mRNA vaccine targeting cytomegalovirus (CMV) that stimulates immune responses by encoding specific viral proteins.
  • In a phase 1 trial, healthy adults who received three doses developed strong neutralizing antibodies and increased memory B cells, which persisted for months.
  • The vaccine effectively triggered robust T-cell responses, indicating its potential for further clinical development to combat CMV, a virus that poses risks, especially to vulnerable populations.
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Background: MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure.

Methods: A messenger RNA (mRNA)-based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine.

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