Document Detail

Correlation between amount of virus with altered nucleotide sequence and the monkey test for acceptability of oral poliovirus vaccine.
MedLine Citation:
PMID:  1846038     Owner:  NLM     Status:  MEDLINE    
Production of live attenuated oral poliomyelitis vaccine (OPV) requires rigorous neurovirulence safety testing of each vaccine lot, currently carried out in monkeys. It has been reported that a change from 472-U to 472-C in the type 3 OPV RNA is associated with an increased histologic lesion score produced upon intraspinal inoculation of the mutant virus in monkeys. We have developed a method, based on polymerase chain reaction, for measuring the relative abundance of these mutant sequences directly in vaccine preparations and used this method to evaluate the proportion of 472-C in 40 different lots of type 3 OPV. Six vaccine lots that had failed the intraspinal monkey neurovirulence test contained a higher proportion of 472-C than all other lots that had passed this test. OPV type 3 virus containing 472-C was rapidly selected during serial passages in African green monkey kidney cells that are used for manufacturing of the vaccine. We have also found that the wild-type poliovirus type 3 strain Leon/37, from which the vaccine strain was originally derived, contained a mixture of 472-U and 472-C sequences. No other mutations in OPV type 3 RNA have been detected by similar assays at position 2034, also associated with attenuation, or at several other positions reported to be altered in some vaccine preparations. Our results suggest that molecular diagnostics may provide a supplement or a potential alternative to animal testing of live attenuated vaccines.
K M Chumakov; L B Powers; K E Noonan; I B Roninson; I S Levenbook
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  88     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1991 Jan 
Date Detail:
Created Date:  1991-02-14     Completed Date:  1991-02-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  199-203     Citation Subset:  IM    
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892.
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MeSH Terms
Animal Testing Alternatives
Base Sequence
Cell Line
Cercopithecus aethiops
Molecular Sequence Data
Oligonucleotide Probes
Poliovirus / genetics*,  isolation & purification
Poliovirus Vaccine, Oral / standards*
Polymerase Chain Reaction / methods
RNA, Viral / genetics,  isolation & purification
Vaccines, Attenuated / standards*
Grant Support
Reg. No./Substance:
0/Oligonucleotide Probes; 0/Poliovirus Vaccine, Oral; 0/RNA, Viral; 0/Vaccines, Attenuated

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