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Plant-made polio type 3 stabilized VLPs-a candidate synthetic polio vaccine.

ABSTRACT: Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6?Å resolution by cryo-electron microscopy and single-particle reconstruction reveals a structure almost indistinguishable from wild-type PV3.Despite the success of current vaccination against poliomyelitis, safe, cheap and effective vaccines remain sought for continuing eradication effort. Here the authors use plants to express stabilized virus-like particles of type 3 poliovirus that can induce a protective immune response in mice transgenic for the human poliovirus receptor.

SUBMITTER: Marsian J

PROVIDER: S-EPMC5557999 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Plant-made polio type 3 stabilized VLPs-a candidate synthetic polio vaccine.

Marsian Johanna J Fox Helen H Bahar Mohammad W MW Kotecha Abhay A Fry Elizabeth E EE Stuart David I DI Macadam Andrew J AJ Rowlands David J DJ Lomonossoff George P GP

Nature communications 20170815 1

Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized virus-like particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation ...[more]

PMID: 28811473

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Project description:BackgroundYemen has faced one of the worst humanitarian crises in the world since the start of the war in 2015. In 2020; 30 Vaccine Derived Polio Virus type 1 (VDPV1) isolates were detected in Saadah governorate. The aims are to characterize the outbreak and address the gaps predisposing the emergence and circulation of VDPV1 in Saadah governorate, Yemen.MethodA retrospective descriptive study of confirmed cases of VDPV1 between January and December 2020 was performed. Surveillance staff collected data from patient cases, contacts, as well as stool specimens that shipped to WHO accredited polio labs. Data of population immunity was also reviewed. The difference in days between the date of sample collection, shipment, and receiving lab result was used to calculate the average of delayed days for lab confirmation.ResultsFrom January to December 2020, a total of 114 cases of acute flaccid paralysis (AFP) were reported from 87% (13/15) districts, and cVDPV1 was confirmed among 26% (30) AFP cases. 75% (21) were < 5 years, 73% (20) had zero doses of Oral Polio Vaccine (OPV). The first confirmed case (3%) was from Saadah city, with paralysis onset at the end of January 2020 followed by 5 cases (17%) in March from another four districts, 8 cases (27%) in April, and 13 (43%) up to December 2020 were from the same five districts in addition to 3 (10%) form three new districts. The lab confirmation was received after an average of 126 days (71-196) from sample collection. The isolates differ from the Sabin 1 type by 17- 30 VP1 nucleotides (nt) and were linked to VDPV1 with 13 (nt) divergence that isolated in July 2020 from stool specimens collected before one year from contacts of an inadequate AFP case reported from Sahar district.ConclusionThe new emerging VDPV1 was retrospectively confirmed after one year of sample collection from Sahar district. Delayed lab confirmation, as well as the response and low immunization profile of children against polio, were the main predisposing factors for cVDPV1 outbreak. This outbreak highlights the need to maintain regular biweekly shipments to referral polio labs in the short-term, and the exploration of other options in the longer-term to enable the Yemen National Lab to fully process national samples itself.

Dataset Information

Plant-made polio type 3 stabilized VLPs-a candidate synthetic polio vaccine.

Publications

Plant-made polio type 3 stabilized VLPs-a candidate synthetic polio vaccine.

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