Genomic modifications in Sabin vaccine strains isolated from vaccination-associated cases, healthy contacts and healthy vaccinees

Abstract

The three attenuated strains developed by A.B. Sabin have been effectively used as an oral live poliovirus vaccine (OPV) to control poliomyelitis in many countries. Although rarely, vaccination-associated paralytic poliomyelitis (VAPP) cases occur with the type 2 and 3 strains, and less frequently with the type 1 strain. The greater number of attenuating mutations in the P1/Sabin strain is probably reflected in the higher safety of this strain in comparison to type 2 and 3 strains. For the P1/Sabin strain, many attenuating mutations were already identified in the 5'-non-coding region (5'NCR), in the capsid proteins coding region, in the 3Dpol coding region, and the 3'-non-coding region (3'NCR). For the P2/Sabin and P3/Sabin strains, one mutation in 5'NCR and another in the capsid proteins coding region have been demonstrated to be important determinations of attenuation, although it has been suggested that other mutations may also have some effect, though minor. Although reverting mutations in attenuating determinants, suppressor mutations, mutations in antigenic sites and genomic recombination have been observed in strains isolated from VAPP cases, the observation of similar genomic modifications in strains isolated from healthy contacts and from healthy vaccinees has supported the view that host factors are also involved in the establishment of the disease. Reverting mutations at nucleotides (nt) 480 (G-->A), 481 (A-->G) and 472 (U-->C) for the P1/Sabin, P2/Sabin and P3/Sabin strains, respectively, have been detected in almost all strains isolated from VAPP cases and also from healthy vaccinees. Although the Sabin vaccine strains have been implicated in rare VAPP cases, recent studies have suggested that the vaccine strains could also trigger the Guillain-Barré syndrome (GBS), transverse myelitis (TM) and facial paralysis.