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Publication Abstract from PubMed

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 A 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.

Structure-based design of glycoprotein subunit vaccines for mumps.,Loomis RJ, Lai YT, Sowers SB, Fisher B, Derrien-Colemyn A, Ambrozak DR, Tsybovsky Y, Crooke SN, Latner DR, Kong WP, Ruckwardt TJ, Plotkin SA, Kwong PD, Mascola JR, Graham BS, Hickman CJ, Stewart-Jones GBE Proc Natl Acad Sci U S A. 2024 Nov 19;121(47):e2404053121. doi: , 10.1073/pnas.2404053121. Epub 2024 Nov 11. PMID:39527740^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.