Structure-based design of glycoprotein subunit vaccines for mumps

Area of Science:

• Virology and Immunology
• Vaccine Development
• Structural Biology

Background:

• Mumps virus (MuV) remains a global public health concern, causing outbreaks despite high vaccination rates.
• Waning immunity and antigenic drift between vaccine strains and circulating wild-type mumps viruses contribute to vaccine ineffectiveness.
• Current measles, mumps, and rubella (MMR) vaccines may require boosting or next-generation alternatives.

Purpose of the Study:

• To engineer novel mumps virus subunit vaccine candidates based on structure-based design.
• To evaluate the immunogenicity and cross-neutralizing potential of stabilized prefusion F (Pre-F) and chimeric Pre-F/HN immunogens.
• To characterize the neutralizing antibody responses elicited by these novel immunogens.

Main Methods:

• Structure-based design was employed to engineer mumps fusion (F) glycoprotein stabilized in its prefusion conformation (Pre-F).
• A chimeric immunogen comprising Pre-F linked to mumps hemagglutinin neuraminidase (HN) was created.
• Crystal structure of mumps Pre-F was determined; monoclonal antibodies were generated and characterized for neutralizing activity against different mumps virus genotypes.

Main Results:

• Both Pre-F antigen and the chimeric Pre-F/HN immunogen elicited potent cross-reactive neutralizing antibody titers against mumps virus genotypes A, G, and H in mice.
• The crystal structure confirmed the stabilization of the mumps Pre-F.
• Isolated antibodies demonstrated neutralization of various mumps virus genotypes, targeting distinct antigenic sites on Pre-F and HN glycoproteins.

Conclusions:

• Engineered mumps Pre-F and chimeric Pre-F/HN immunogens are effective in eliciting broad cross-neutralizing antibody responses.
• These novel immunogens represent promising candidates for boosting existing MMR-induced immunity or as next-generation mumps vaccines.
• Further development could lead to improved control of mumps outbreaks in highly immunized populations.