In a study published by The Journal of Infectious Diseases, aimed to improve the MF59-adjuvanted gB subunit (gB/MF59) vaccine, demonstrating about 50% efficacy against the currently incurable HCMV. Improvements to this vaccine could lead to a vaccine suitable for licensure. In this context, the mRNA-1647 vaccine demonstrated multifaceted and long-lasting antibody responses specific to HCMV. While the vaccine generated lower levels of gB-specific IgG antibodies, it produced higher levels of neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC) response.
“It was interesting that the overall gB-specific IgG elicited is lower after mRNA-1647 immunization compared to the gB/MF59 vaccine, yet certain functional responses like neutralization and ADCC are higher,” according to investigator Sallie R Permar, MD, PhD. “From this finding, distinct specificity or types of antibody responses are elicited by each vaccine, potentially due to a distinct conformation of gB expressed from an mRNA compared to a soluble protein.”
The messenger RNA (mRNA)-1647 vaccine induced and enhanced immunoglobulin G (IgG) responses specific to HCMV in both seronegative and seropositive individuals, respectively. This included the generation of neutralizing antibodies and Fc-mediated effector functions. However, gB-specific IgG responses were less robust than pentameric complex (PC)-specific IgG responses. Additionally, the levels of gB-specific IgG and antibody-dependent cellular phagocytosis induced by mRNA-1647 were lower than those triggered by the gB/MF59 vaccine. Despite this, mRNA-1647 demonstrated superior performance in eliciting higher neutralizing and ADCC responses.
3 Key Takeaways
- Compared to the gB/MF59 vaccine, mRNA-1647 induces a more potent immune response characterized by higher levels of neutralizing antibodies and ADCC, despite lower gB-specific IgG antibody levels.
- This technology enables the immune system to recognize and combat the virus more effectively, potentially leading to more successful vaccine candidates in the future.
- Given the global prevalence of HCMV and its significant health impacts, particularly in congenital infections, advancing vaccine research to include those already exposed to the virus is crucial for developing a universally effective vaccine.
“The results indicated that the mRNA vaccine currently in phase 3 testing elicits a different kind of responses than previous vaccines which had partial efficacy, providing hope that it will improve on the results of prior vaccine candidates,” states Sallie R.Permar MD, PhD. “This vaccine and other CMV vaccine candidates should continue to be tested in CMV seropositive populations, as the majority of congenital CMV transmission worldwide occurs in these populations and the most globally successful CMV vaccine will need to be effective in that setting.”
Investigators evaluated the neutralizing and Fc-mediated IgG effector antibody responses triggered by mRNA-1647 in individuals with and without previous HCMV exposure, who were part of a pioneering human clinical trial, for 1 year after receiving their third vaccination, utilizing a systems serology methodology. In addition, we contrasted the maximum anti-gB antibody responses among seronegative recipients of mRNA-1647 with those of seronegative participants who received the gB/MF59 vaccine.
Overall, the study of the mRNA-1647 vaccine represents a breakthrough in HCMV vaccination efforts, with the potential to change current approaches to prevent the virus. The ability of this vaccine to get stronger and more effective immune responses underscores the role of mRNA technology in fighting infectious diseases. As the vaccine progresses through further clinical trials, its development, and potential licensure could improve HCMV prevention strategies.
Reference
1. Hu X, Karthigeyan K, Herbek S, Valencia S, Jenks J, et. al. Human cytomegalovirus mRNA-1647 vaccine candidate elicits potent and broad neutralization and higher antibody-dependent cellular cytotoxicity responses than the gB/MF59 vaccine The Journal of Infectious Diseases. Published February 7, 2024. Accessed February 14, 2024.
