{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:26:07Z","timestamp":1781101567502,"version":"3.54.1"},"reference-count":30,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,10,9]]},"abstract":"<jats:p>RNA viruses exist as quasispecies, heterogeneous and dynamic mixtures of mutants having one or more consensus sequences. An adequate description of the genomic structure of such viral populations must include the consensus sequence(s) plus a quantitative assessment of sequence heterogeneities. For example, in quality control of live attenuated viral vaccines, the presence of even small quantities of mutants or revertants may indicate incomplete or unstable attenuation that may influence vaccine safety. Previously, we demonstrated the monitoring of oral poliovirus vaccine with the use of mutant analysis by PCR and restriction enzyme cleavage (MAPREC). In this report, we investigate genetic variation in live attenuated mumps virus vaccine by using both MAPREC and a platform (DNA MassArray) based on matrix-assisted laser desorption\/ionization time-of-flight (MALDI-TOF) mass spectrometry. Mumps vaccines prepared from the Jeryl Lynn strain typically contain at least two distinct viral substrains, JL1 and JL2, which have been characterized by full length sequencing. We report the development of assays for characterizing sequence variants in these substrains and demonstrate their use in quantitative analysis of substrains and sequence variations in mixed virus cultures and mumps vaccines. The results obtained from both the MAPREC and MALDI-TOF methods showed excellent correlation. This suggests the potential utility of MALDI-TOF for routine quality control of live viral vaccines and for assessment of genetic stability and quantitative monitoring of genetic changes in other RNA viruses of clinical interest.<\/jats:p>","DOI":"10.1073\/pnas.211423298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:10Z","timestamp":1027679650000},"page":"12097-12102","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":36,"title":["Quantitative mutant analysis of viral quasispecies by chip-based matrix-assisted laser desorption\/ ionization time-of-flight mass spectrometry"],"prefix":"10.1073","volume":"98","author":[{"given":"Georgios","family":"Amexis","sequence":"first","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM 470, Rockville, MD 20852; SEQUENOM, Inc., Genomics Department, 3595 John Hopkins Court, San Diego, CA 92121; and Aventis Pasteur, 1541 Avenue Marcel Merieux, 69280 Marcy l'Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Oeth","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM 470, Rockville, MD 20852; SEQUENOM, Inc., Genomics Department, 3595 John Hopkins Court, San Diego, CA 92121; and Aventis Pasteur, 1541 Avenue Marcel Merieux, 69280 Marcy l'Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Abel","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM 470, Rockville, MD 20852; SEQUENOM, Inc., Genomics Department, 3595 John Hopkins Court, San Diego, CA 92121; and Aventis Pasteur, 1541 Avenue Marcel Merieux, 69280 Marcy l'Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Ivshina","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM 470, Rockville, MD 20852; SEQUENOM, Inc., Genomics Department, 3595 John Hopkins Court, San Diego, CA 92121; and Aventis Pasteur, 1541 Avenue Marcel Merieux, 69280 Marcy l'Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Pelloquin","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM 470, Rockville, MD 20852; SEQUENOM, Inc., Genomics Department, 3595 John Hopkins Court, San Diego, CA 92121; and Aventis Pasteur, 1541 Avenue Marcel Merieux, 69280 Marcy l'Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Cantor","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM 470, Rockville, MD 20852; SEQUENOM, Inc., Genomics Department, 3595 John Hopkins Court, San Diego, CA 92121; and Aventis Pasteur, 1541 Avenue Marcel Merieux, 69280 Marcy l'Etoile, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Braun","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM 470, Rockville, MD 20852; 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