Is it time to switch to a formulation other than the live attenuated poliovirus vaccine to prevent poliomyelitis?

Figures

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  Figure 1. Schematic representation of the oral transmission of polioviruses (contained in water or food) and their colonization of the gastrointestinal tract. Major risk factors for poliovirus transmission include poor sanitation and hygiene conditions, high population density and tropical/subtropical climate. (A) Polioviruses infect humans by the fecal-oral route. This acid resistant virus can travel through the stomach (pH: 1–2) and reach the intestine. (B) Once in the intestine (pH: 7.3–7.7), the poliovirus (WPV or OPV) meets the commensal microbiota and the first antiviral defense such as the mucus layer, protective peptides, immune cells expressing CD103 and KLRG1 and is able to bind the E-cadherin found at the surface of epithelial cells (for details see (4, 5). However, the interaction of poliovirus capsid with lipopolysaccharide of bacteria enhances virion stability and receptor attachment (6, 7). (C) The polioviruses which manage to pass the first barrier of defense encounter a second barrier which is the intestinal epithelium, protecting the host against intruder transmigration. On this intestinal epithelium, polioviruses found their CD155 receptor on M cells. (D) Simplified…

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  Figure 2. Passage histories from the wild type polioviruses to isolate the Sabin OPV1, OPV2 and OPV3. The viruses were replicated either in vivo on monkey (MK) or mouse (Mo) or in vitro. The in vitro cultures used cells from different tissues (cynomolgus monkey kidney cells, rhesus monkey testicular or skin tissues). At the different stages of the selection, the strains where tested for neurovirulence in cynomolgus monkeys inoculated intraspinally and those possessing the least residual neurovirulence, were selected. Culture on chik (Chik) embryos, were also used for other strains (CHAT and Cox) replicated in vivo in human (Hu) and was used for selection of the CHAT strain. Large batches of the three type of Sabin OPVs were produced by the MSD company using cultures of monkey kidney cells transformed by the SV40 susceptible to poliovirus infection and replication.

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  Figure 3. Schematic representation of the genomic organization of the wild type poliovirus (Mahoney strain) and the Sabin live attenuated poliovirus vaccine. (Upper panel) Mahoney virus. P1 is the precursor of the capsid proteins; P2 and P3 are the precurors of the non-capsid proteins. The genome segment from nucleotide 743 to 3,832 encodes a polyprotein precursor amino acids 1 to 1,030. Non-coding region = NCR (also designed UTR for untranslated region); nuclotide = nt. (Middle panel) Sabin OVP1 strain. The complete nucleotide sequence of the attenuated Sabin OPV1 compared with the WPV Mahoney strain (32), identified 57 base substitutions to be scattered all over the genome. Of these, 21 were missense mutations (red triangle) resulting in amino acid changes in a number of viral proteins, especially in the NH2-terminal half of the VP1 capsid protein, involved in attenuation (each mutation indicated by a red star). The location of the principal nucleotide substitutions leading to the attenuated phenotype is indicated in blue (A480G, G935U, U2438A, G2795A, and C2879U for the Sabin OPV1). (Lower panel) Location of the principal nucleotide substitutions leading to the attenuated phenotype of…

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  Figure 4. Schematic representation of the number of polio cases by comparing the cases linked to wild poliovirus and to the vaccine based on the live attenuated virus. (A) Number of annual cases of polio in the world that have been linked to the wild virus (currently only WPV1) and to the different cVDPVs viruses. (B) Number of cumulative cases of polio in the world linked to the wild virus (currently only WPV1) and to the different cVDPVs (cVDPV1, cVDPV2 and cVDPV3) viruses between January 2018 and May 2023. The values used to make this figure are those available via the ECDC (https://gis.ecdc.europa.eu/portal/apps/dashboards; accessed on June 1, 2023).

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  Figure 5. Representative examples of enterovirus sequences showing high percent identity with the nucleotide sequence 461–519 of cVDPV2 revertant. The nucleotide sequence surrounding the position 481 from an OPV2 which has loss OPV2 attenuation (cVDPV2) was blasted against the complete Base NR database to search for possible identity with other enteroviruses. Several sequences from enteroviruses contain a G within a sequence of high similarity with cVDPV2, were identified including WPV3 (WPV3 ISR_1976-12b; GenBank accession OP137305), ENV-C (Enterovirus C strain Polozj-3; GenBank accession MZ546188), CAV-A20 (Coxsackievirus A20 strain IH Pool 35; GenBank accession AF465514), ENV-C99 (Enterovirus C99 strain MAD-3185-2011; GenBank accession OK570208). Notably, a sequence from rhinovirus, HRV (Antwerp rhinovirus 98/99 isolate 99028352; GenBank accession DQ316308), shows 97% identity with cVDPV2 but contains an A481 as for the OPV2 strain.

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  Figure 6. Recombinant cVDPVs. Schematic representation of the genomic organization of some cVDPVs that have been isolated during different outbreaks between 1982 and 2005 in various geographic areas (Hisponiola, the Philippines, Egypt, Nigeria, Madagascar, China). The outbreaks corresponded to the emergence of mutated OPV1, OPV2, or OPV3, which had recombined with either human enteroviruses (ENV-C) including Coxackie A (CV-A11, CV-A13, or CV-A17). Data are adapted, modified and/or summarized from references (84, 85, 96, 136, 139). For example, one of the cVDPVs isolated in Madagascar in 2005 was a mosaic genome composed by a mutated OPV2 with a recombinant 5′-end derived from Coxsackie A-13, a sequence encoding non structural proteins derived from Coxsackie A-17 and a 3′-end from OPV3. More recently, a strain was isolated in London, UK, that showed a recombinant genetic structure between cVDPV2 (with reversion of the two main OPV2 attenuation mutations) and an unidentified enterovirus C species with a crossover point at nucleotide 5,139 (142), not shown.