Comparative Study on Monovalent, Bivalent, and Pentavalent HCMV gB mRNA-LNP Vaccines: Immunogenicity Insights

Human cytomegalovirus (HCMV) is a widespread pathogen that poses serious health risks, especially to immunocompromised individuals and newborns. Thus, developing an effective vaccine against HCMV is a pressing global health need. A recent study delves into this by comparing the immunogenicity of monovalent, bivalent, and pentavalent HCMV gB mRNA-LNP vaccines in the New Zealand White rabbit model.

Comparing Immunogenicity of Different HCMV gB mRNA-LNP Vaccines

The study focused on understanding whether a vaccine including multiple gB genotypes could elicit a broader humoral immunity against multi-genotypic HCMV infections compared to the monovalent gB immunogen. In the study, 18 female rabbits were immunized with monovalent gB1, bivalent gB1/gB3, or pentavalent gB1/gB2/gB3/gB4/gB5 lipid nanoparticle encapsulated nucleoside modified RNA (mRNA) LNP vaccines.

Interestingly, the findings reveal that the monovalent vaccine elicited the highest binding response at peak immunogenicity, and the bivalent and pentavalent vaccines did not significantly increase the IgG binding breadth. This suggests that the multivalent vaccines did not demonstrate a higher magnitude or breadth of the IgG response to the gB ectodomain or cell-associated gB compared to that of the monovalent vaccine.

Neutralizing Antibody Response and Fc-Mediated Effector Function

Equally important, the study also evaluated the neutralizing antibody response and Fc-mediated effector function. The multivalent vaccines did not elicit a broader neutralizing antibody response or an advantage for the breadth of Fc-mediated effector function compared to the monovalent vaccine.

This indicates that multivalent vaccines did not show an increase in the breadth of neutralization activity and antibody-dependent cellular phagocytosis against HCMV strains encoding distinct gB genotypes.

Robust T Cell Response Induced by Pentavalent Vaccine

However, there was one area where the pentavalent vaccine stood out. The pentavalent vaccine demonstrated the highest T cell response against gB-2 at week 6, indicating a more robust T cell response. Peripheral blood mononuclear cell-derived gB2 specific T cell responses elicited by multivalent vaccines were of a higher magnitude compared to that of monovalent vaccinated animals against a vaccine mismatched gB genotype at peak immunogenicity.

Yet no statistical differences were observed in T cell response against gB3 and gB5 variable regions among the three vaccine groups. This indicates that while the pentavalent vaccine may induce a stronger T cell response, it does not necessarily mean a broader immune response against different HCMV gB genotypes.

Implications for HCMV Vaccine Development

The findings of this study suggest that the inclusion of multivalent gB antigens is not an effective strategy to increase the breadth of anti-HCMV gB antibody and T cell responses. This is an important insight for HCMV vaccine development. It implies that simply adding more gB genotypes into a vaccine may not necessarily lead to broader protection against HCMV.

Understanding how to increase the HCMV vaccine protection breadth will indeed be essential in improving vaccine efficacy. It is clear from this study that more research is required to develop an HCMV vaccine that can provide broad and robust protection against this common and potentially dangerous virus.