Assay for identification of heterozygous single-nucleotide polymorphism (Ala67Thr) in human poliovirus receptor gene

Nandi, Shyam Sundar; Sharma, Deepa Kailash; Deshpande, Jagadish M.

doi:10.4103/0971-5916.193281

Cited by 5 publications

(3 citation statements)

References 20 publications

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“…The impressive reduction in EVA71-associated illness in the 1 and 2 year follow up highlights the importance of vaccination, although there remain safety concerns surrounding the large-scale production of live virus prior to inactivation. Indeed, there have been several instances of inadvertent release of infectious poliovirus (PV) into the environment as a consequence of vaccine manufacture [7][8][9][10][11][12]. The implementation of alternative vaccine candidates, such as peptide, subunit or virus-like particle (VLP) vaccines has shown promising results in early-stage trials [13][14][15][16][17][18][19][20], and these approaches have improved safety as infectious material is not required during vaccine production.…”

Section: Introductionmentioning

confidence: 99%

Production of antigenically stable enterovirus A71 virus-like particles in Pichia pastoris as a vaccine candidate

Kingston

Snowden

Martyna

et al. 2023

Journal of General Virology

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Enterovirus A71 (EVA71) causes widespread disease in young children with occasional fatal consequences. In common with other picornaviruses, both empty capsids (ECs) and infectious virions are produced during the viral lifecycle. While initially antigenically indistinguishable from virions, ECs readily convert to an expanded conformation at moderate temperatures. In the closely related poliovirus, these conformational changes result in loss of antigenic sites required to elicit protective immune responses. Whether this is true for EVA71 remains to be determined and is the subject of this investigation. We previously reported the selection of a thermally resistant EVA71 genogroup B2 population using successive rounds of heating and passage. The mutations found in the structural protein-coding region of the selected population conferred increased thermal stability to both virions and naturally produced ECs. Here, we introduced these mutations into a recombinant expression system to produce stabilized virus-like particles (VLPs) in Pichia pastoris. The stabilized VLPs retain the native virion-like antigenic conformation as determined by reactivity with a specific antibody. Structural studies suggest multiple potential mechanisms of antigenic stabilization, however, unlike poliovirus, both native and expanded EVA71 particles elicited antibodies able to directly neutralize virus in vitro. Therefore, anti-EVA71 neutralizing antibodies are elicited by sites which are not canonically associated with the native conformation, but whether antigenic sites specific to the native conformation provide additional protective responses in vivo remains unclear. VLPs are likely to provide cheaper and safer alternatives for vaccine production and these data show that VLP vaccines are comparable with inactivated virus vaccines at inducing neutralising antibodies.

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Section: Introductionmentioning

confidence: 99%

Production of antigenically stable enterovirus A71 virus-like particles in Pichia pastoris as a vaccine candidate

Kingston

Snowden

Martyna

et al. 2023

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…The heterozygous single nucleotide polymorphism (SNP) (Ala67Thr) in CD155 gene has been reported in healthy population (6.8 to 8.5%) and the incidence has been shown to be significantly higher in polio paresis (13.3%) and progressive muscular atrophy (20%) patients89. Nandi and colleagues10 in this issues have reported development of an SNP assay to detect the single nucleotide substitution (GCGaACG) in CD155/PVR gene. The assay seems to be suitable for large scale screening of PPS samples for identification of heterozygous SNP in the CD155/PVR gene10.…”

mentioning

confidence: 99%

“…Nandi and colleagues10 in this issues have reported development of an SNP assay to detect the single nucleotide substitution (GCGaACG) in CD155/PVR gene. The assay seems to be suitable for large scale screening of PPS samples for identification of heterozygous SNP in the CD155/PVR gene10. However, the screening for PVR gene polymorphism (Ala67Thr) should be further confirmed on a large sample of PPS patients in different population groups in India.…”

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confidence: 99%