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Journal of Virology, January 2005, p. 1062-1070, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1062-1070.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Spread of Vaccine-Derived Poliovirus from a Paralytic Case in an Immunodeficient Child: an Insight into the Natural Evolution of Oral Polio Vaccine

E. A. Cherkasova,1,2 M. L. Yakovenko,2 G. V. Rezapkin,1 E. A. Korotkova,2 O. E. Ivanova,3 T. P. Eremeeva,3 L. I. Krasnoproshina,4 N. I. Romanenkova,5 N. R. Rozaeva,5 L. Sirota,1 V. I. Agol,2,3 and K. M. Chumakov1*

Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland,1 A. N. Belozersky Institute of Physical-Chemical Biology, Moscow State University,2 I. I. Mechnikov Institute of Vaccines and Sera, Moscow,4 M. P. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Russian Academy of Medical Sciences, Moscow Region,3 St. Petersburg Pasteur Institute, St. Petersburg, Russia5

Received 15 July 2004/ Accepted 3 September 2004

Sabin strains used in the manufacture of oral polio vaccine (OPV) replicate in the human organism and can give rise to vaccine-derived polioviruses. The increased neurovirulence of vaccine derivatives has been known since the beginning of OPV use, but their ability to establish circulation in communities has been recognized only recently during the latest stages of the polio eradication campaign. This important observation called for studies of their emergence and evolution as well as extensive surveillance to determine the scope of this phenomenon. Here, we present the results of a study of vaccine-derived isolates from an immunocompromised poliomyelitis patient, the contacts, and the local sewage. All isolates were identified as closely related and slightly evolved vaccine derivatives with a recombinant type 2/type 1 genome. The strains also shared several amino acid substitutions including a mutation in the VP1 protein that was previously shown to be associated with the loss of attenuation. Another mutation in the VP3 protein resulted in altered immunological properties of the isolates, possibly facilitating virus spread in immunized populations. The patterns and rates of the accumulation of synonymous mutations in isolates collected from the patient over the extended period of excretion suggest either a substantially nonuniform rate of mutagenesis throughout the genome, or, more likely, the strains may have been intratypic recombinants between coevolving derivatives with different degrees of divergence from the vaccine parent. This study provides insight into the early stages of the establishment of circulation by runaway vaccine strains.

* Corresponding author. Mailing address: Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM-470, Rockville, MD 20852-1448. Phone: (301) 594-3720. Fax: (301) 827-4622. E-mail: chumakov{at}cber.fda.gov.

Journal of Virology, January 2005, p. 1062-1070, Vol. 79, No. 2
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.2.1062-1070.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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