Comparative study of poliovirus excretion after vaccination of infants with two oral polio vaccines prepared on vero cells or on primary monkey kidney cells

Abstract

A comparative study was designed to assess the bioequivalence of 2 oral poliovaccines (OPV) produced on 2 different cell systems: primary monkey kidney (PMK) cells and the Vero cell line. The Vero cell line has been used to overcome the problem of obtaining a regular supply of high quality monkeys that are devoid of latent viruses. For this study, 9 children were vaccinated with PMK-OPV and 12 children with Vero-OPV. The comparison covered poliovirus excretion, reversion of polioviruses in the 5'-noncoding region, and immunogenicity. Major molecular markers in the 5'-noncoding region related to neurovirulence already had been identified at position 480 for type 1, position 481 for type 2, and position 472 for type 3 poliovirus. Two nucleic-acid based methods were designed for studying these positions: a RT-PCR followed by sequencing, which required preliminary culture and cloning; and a type-specific nested PCR followed by sequencing, which enabled direct detection and genotyping of polioviruses. Twenty-eight stool specimens were analyzed by this second method with no PCR inhibition problem. The use of Vero cell line did not modify the global pattern of poliovirus excretion, reversion frequency, or seroconversion. These results provide additional support for the use of the well-characterized Vero cell line in OPV manufacturing.

Use of a Novel Real-Time PCR Assay To Detect Oral Polio Vaccine Shedding and Reversion in Stool and Sewage Samples after a Mexican National Immunization Day

“…Mexico has recently changed from propagation of OPV seed strains in primary monkey kidney cells to Vero cells (16). However, there are no convincing data that propagation in Vero cells increases the stability of OPV, and indeed, one study showed no modification in the pattern of poliovirus excretion when children vaccinated with OPV propagated in Vero cells were compared with children vaccinated with OPV propagated in primary monkey kidney cells (11). We were unable to confirm the absence of the point mutations by sequencing our samples, due to the low concentrations of virus present.…”

Expert Review on Poliovirus Immunity and Transmission

“…High type 3 and type 1 estimates (57,59,70,72) most likely represent an artifact of poor take of the first two tOPV doses or low sample size. (71) The lowest estimate of 0.07 from Cohen-Abbo et al (70) may partially reflect an artifact of the low sensitivity of poliovirus detection at 30 days after the challenge, although the study achieved higher isolation rates for the other serotypes. The remaining estimates provide the best data for relative susceptibility after two or more LPV infections and range from 0.09 to 0.44.…”

“…high seropositivity after the first dose. The type 1 data from Ghendon and Sanakoyeva (24) and type 2 data from Mallet et al (71) and Samoilovich et al (72) include only seropositive subjects at the time of challenge after receipt of a single OPV dose, with relative susceptibility estimates ranging from 0.20 to 0.55.…”

“…Other estimates based mostly on results from responders to the first dose include type 2 results from Cohen-Abbo et al (70) (95% seroconverted), Dong et al (50) (96% seropositive at time of challenge), Maldonado et al (73) (90% seroconverted), and type 1 results from Mallet et al (71) (94% seropositive), which yield relative susceptibility estimates ranging from 0.09 to 0.45. Relative susceptibility estimates exceeding 1 occur for type 3 in some studies (57,59,70) because the second dose of tOPV typically yields a better type 3 response than the first tOPV dose due to interference between serotypes for the first tOPV dose.…”

“…(14) We assess the weight of the evidence for 1 LPV infection as high with respect to design, quality, and consistency, but moderate with respect to relevance, because no study measures virus exposure as it would occur in a natural setting (Table III). Eighteen OPV challenge studies (20,22,24−26,45,54,56,58,60,61,64−66,68,70−72,74−76) report excretion results for multiple OPV dose recipients, with 10 studies (24,25,45,54,64,68,(70)(71)(72)75) meeting the inclusion criteria. High type 3 and type 1 estimates (57,59,70,72) most likely represent an artifact of poor take of the first two tOPV doses or low sample size.…”