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Detection of Neutralization-sensitive Epitopes in Antigens Displayed on Virus-Like Particle VLP-Based Vaccines Using a Capture Assay
Published on: February 10, 2022
Identification of conformational neutralization sites on the fusion protein of mumps virus
Maja Šantak1, Claes Örvell2, Tanja Košutić Gulija1
1Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, Zagreb 10 000, Croatia.
Abstract:
In spite of the success of the mumps vaccination, recent mumps outbreaks have been reported even among individuals with a history of mumps vaccination. For a better understanding of why the vaccination failed in cases of vaccinees who fell ill during recent mumps outbreaks, the immunological events during infection and/or vaccination should be better defined. In the work presented here we sought to identify new neutralization sites on the mumps virus surface glycoproteins. By using anti-mumps mAbs, three amino acid positions at residues 221, 323 and 373 in the F protein of mumps virus were shown to be located in at least two conformational neutralization epitopes. mAbs that specifically target these sites effectively neutralized mumps virus in vitro. The newly acquired glycosylation site at position 373 or loss of the existing one at position 323 was identified as the mechanism behind the escape from the specific mAbs. Based on the findings of this study, we suggest that the influence of the antigenic structure of the F protein should not be ignored in a thorough investigation of the underlying mechanism of the mumps vaccine failure or when making a strategy for development of a new vaccine.
Insights
Recent mumps outbreaks occur despite vaccination. This study identified key neutralization sites on the mumps virus F protein, revealing how the virus may evade vaccine-induced immunity.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Despite successful mumps vaccination programs, recent outbreaks have occurred in vaccinated populations.
- Understanding vaccine failure mechanisms is crucial for improving mumps prevention strategies.
Purpose of the Study:
- To identify novel neutralization sites on mumps virus surface glycoproteins.
- To investigate the immunological basis for mumps vaccine failure.
Main Methods:
- Utilized anti-mumps monoclonal antibodies (mAbs) to map neutralization epitopes on the F protein.
- Analyzed amino acid positions and glycosylation changes affecting viral neutralization.
Main Results:
- Identified three key amino acid positions (221, 323, 373) in the F protein as part of conformational neutralization epitopes.
- Demonstrated that mAbs targeting these sites effectively neutralized mumps virus in vitro.
- Found that altered glycosylation at positions 323 or 373 contributes to viral escape from specific mAbs.
Conclusions:
- The antigenic structure of the mumps virus F protein plays a significant role in vaccine efficacy.
- Findings provide insights into mumps vaccine failure mechanisms and inform future vaccine development strategies.

