Structure-based design of glycoprotein subunit vaccines for mumps Article Swipe
Rebecca J. Loomis
,
Yen‐Ting Lai
,
Sun B. Sowers
,
Brian E. Fisher
,
Alexandrine Derrien-Colemyn
,
David R. Ambrozak
,
Yaroslav Tsybovsky
,
Stephen N. Crooke
,
Donald R. Latner
,
Wing‐Pui Kong
,
Tracy J. Ruckwardt
,
S. A. Plotkin
,
Peter D. Kwong
,
John R. Mascola
,
Barney S. Graham
,
Carole J. Hickman
,
Guillaume B. E. Stewart-Jones
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2404053121
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.1073/pnas.2404053121
Mumps virus (MuV) is a highly contagious paramyxovirus that is endemic in most regions of the world and continues to cause outbreaks even in highly immunized populations. Outbreaks of mumps in countries with high measles, mumps, and rubella vaccination coverage have been attributed to waning immunity and antigenic differences between the Jeryl Lynn vaccine strain (genotype A) and circulating wild-type viruses. To obtain a subunit vaccine, we used structure-based design to engineer the mumps fusion (F) glycoprotein stabilized in its prefusion conformation (Pre-F) as well as a chimeric immunogen comprising Pre-F linked to mumps hemagglutinin neuraminidase (HN); in mice, both Pre-F antigen and the chimeric antigen elicited potent cross-reactive plaque reducing neutralizing titers to genotypes A, G, and H mumps. A crystal structure of mumps Pre-F at 2.16 Å resolution validated the stabilization strategy, while a post-fusion form of F was engineered as a comparator. Monoclonal antibodies to mumps Pre-F and HN were isolated from immunized mice; 7 of 14 Pre-F-specific antibodies and 9 of 15 HN-specific antibodies were capable of neutralizing genotype G MuV with a range of potencies. Additionally, 7 of 14 Pre-F-specific antibodies neutralized genotype A mumps. Structural and binding analyses of Pre-F-specific antibodies revealed binding to four discrete neutralizing antigenic sites and binding analyses of HN-specific antibodies revealed binding to five discrete neutralizing antigenic sites. Overall, the PreF and the chimeric Pre-F/HN immunogens are promising candidates to boost MMR-elicited immunity to mumps or as a next-generation vaccine.
Related Topics
Concepts
Virology
Mumps virus
Antigen
Mumps vaccine
Immunogen
Epitope
Biology
Antibody
Immunogenicity
Vaccination
Monoclonal antibody
Rubella
Virus
Immunology
Measles
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1073/pnas.2404053121
- OA Status
- hybrid
- Cited By
- 2
- References
- 45
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4404236724
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4404236724Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1073/pnas.2404053121Digital Object Identifier
- Title
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Structure-based design of glycoprotein subunit vaccines for mumpsWork title
- Type
-
articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-11-11Full publication date if available
- Authors
-
Rebecca J. Loomis, Yen‐Ting Lai, Sun B. Sowers, Brian E. Fisher, Alexandrine Derrien-Colemyn, David R. Ambrozak, Yaroslav Tsybovsky, Stephen N. Crooke, Donald R. Latner, Wing‐Pui Kong, Tracy J. Ruckwardt, S. A. Plotkin, Peter D. Kwong, John R. Mascola, Barney S. Graham, Carole J. Hickman, Guillaume B. E. Stewart-JonesList of authors in order
- Landing page
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https://doi.org/10.1073/pnas.2404053121Publisher landing page
- Open access
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YesWhether a free full text is available
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hybridOpen access status per OpenAlex
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https://doi.org/10.1073/pnas.2404053121Direct OA link when available
- Concepts
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Virology, Mumps virus, Antigen, Mumps vaccine, Immunogen, Epitope, Biology, Antibody, Immunogenicity, Vaccination, Monoclonal antibody, Rubella, Virus, Immunology, MeaslesTop concepts (fields/topics) attached by OpenAlex
- Cited by
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2Total citation count in OpenAlex
- Citations by year (recent)
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2025: 2Per-year citation counts (last 5 years)
- References (count)
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45Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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