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15 May 2006

Volume 193, Number 10
The Journal of Infectious Diseases 2006;193:1344–1349
© 2006 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2006/19310-0002$15.00
DOI: 10.1086/503366
MAJOR ARTICLE

Analysis of Reversions in the 5′‐Untranslated Region of Attenuated Poliovirus after Sequential Administration of Inactivated and Oral Poliovirus Vaccines

Majid Laassri,1

Kathleen Lottenbach,3

Robert Belshe,3

Margaret Rennels,2

Stanley Plotkin,4 and

Konstantin Chumakov1

1Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, and 2University of Maryland School of Medicine, Baltimore, Maryland; 3Saint Louis University, Saint Louis, Missouri; 4University of Pennsylvania and Sanofi Pasteur, Doylestown

Replication of Sabin strains used in oral poliovirus vaccine (OPV) in the intestines of vaccine recipients leads to reversions that increase virus neurovirulence. Previously, a small study reported that prior immunization with inactivated poliovirus vaccine (IPV) resulted in faster accumulation of revertant virus, thus potentially increasing the risk of vaccine‐associated paralytic poliomyelitis. We studied the impact that prior immunization with IPV and OPV has on shedding of revertant virus by healthy infants. By polymerase chain reaction (PCR), we amplified full‐length poliovirus genomes directly from stool specimens from unimmunized infants and from infants previously immunized with IPV or OPV. The amplicons were used to quantify reversions in the 5′‐untranslated region, using oligonucleotide microarray hybridization. Nearly all 140 samples that were PCR positive contained varying amounts of revertants of all 3 poliovirus serotypes. Polioviruses of Sabin types 2 and 3 reverted more easily than those of type 1. Prior vaccination with IPV did not increase the proportion of revertants after OPV administration.

Received 5 August 2005; accepted 28 October 2005; electronically published 4 April 2006.

  • (See the editorial commentary by Kew, on pages 1341–3.)

Reprints or correspondence: Dr. Konstantin Chumakov, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike HFM‐470, Rockville, MD 20852 ().

Cited by

Christopher H. Logue, Brian J. Sheahan, Gregory J. Atkins. (2008) The 5′ untranslated region as a pathogenicity determinant of Semliki Forest virus in mice. Virus Genes 36:2, 313-321
Online publication date: 1-May-2008.
CrossRef
Majid Laassri, Clement A. Meseda, Ollie Williams, Michael Merchlinsky, Jerry P. Weir, Konstantin Chumakov. (2007) Microarray assay for evaluation of the genetic stability of modified vaccinia virus Ankara B5R gene. Journal of Medical Virology 79:6, 791-802
Online publication date: 1-Jul-2007.
CrossRef

  • Potential conflicts of interest: S.P. is the executive adviser to the CEO of Sanofi Pasteur, and M.R. is the chairperson of the multicenter vaccine safety trial monitoring board for Sanofi Pasteur. All other authors report no conflicts of interest or commercial associations.

    Financial support: Defense Advanced Research Projects Agency (grant to K.C.); National Vaccine Program Office (grant to K.C.); National Institute of Allergy and Infectious Diseases (contracts NO1‐AI‐45250 and NO1‐AI‐45251 with R.B. and M.R.).

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