Scientific Publications by FDA Staff

J Virol 2005 Jan;79(2):1062-70

Spread of vaccine-derived poliovirus from a paralytic case in an immunodeficient child: an insight into the natural evolution of oral polio vaccine.

Cherkasova EA, Yakovenko ML, Rezapkin GV, Korotkova EA, Ivanova OE, Eremeeva TP, Krasnoproshina LI, Romanenkova NI, Rozaeva NR, Sirota L, Agol VI, Chumakov KM

Chumakov KM, US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow, Russia II Mechnikov Vaccine & Serum Inst, Moscow, Russia Russian Acad Med Sci, MP Chumakov Inst Poliomyeltitis & Viral Encephali, Moscow, Moscow Region, Russia St Petersburg Pasteur Inst, St Petersburg, Russia

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.