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

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 viruslike 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

Plant-made vaccines in support of the Millennium Development Goals

Vaccines are one of the most successful public health achievements of the last century. Systematic immunisation programs have reduced the burden of infectious diseases on a global scale. However, there are limitations to the current technology, which often requires costly infrastructure and long lead times for production. Furthermore, the requirement to keep vaccines within the cold-chain throughout manufacture, transport and storage is often impractical and prohibitively expensive in developing countries—the very regions where vaccines are most needed. In contrast, plant-made vaccines (PMVs) can be produced at a lower cost using basic greenhouse agricultural methods, and do not need to be kept within such narrow temperature ranges. This increases the feasibility of developing countries producing vaccines locally at a small-scale to target the specific needs of the region. Additionally, the ability of plant-production technologies to rapidly produce large quantities of strain-specific vaccine demonstrates their potential use in combating pandemics. PMVs are a proven technology that has the potential to play an important role in increasing global health, both in the context of the 2015 Millennium Development Goals and beyond

Percentage of SNPs (type 1 error) above HLOD thresholds using PedCut followed by two-point parametric linkage analyses assuming dominant and recessive models and nonparametric linkage analysis using the ‘all’ and ‘pairs’ statistics.

<p>Percentage of SNPs (type 1 error) above HLOD thresholds using PedCut followed by two-point parametric linkage analyses assuming dominant and recessive models and nonparametric linkage analysis using the ‘all’ and ‘pairs’ statistics.</p

Percentage of SNPs (type 1 error) above parametric HLOD and nonparametric LOD thresholds using PedCut followed by multipoint parametric linkage analyses assuming dominant and recessive models and nonparametric linkage analysis using the ‘all’ and ‘pairs’ statistics.

<p>Percentage of SNPs (type 1 error) above parametric HLOD and nonparametric LOD thresholds using PedCut followed by multipoint parametric linkage analyses assuming dominant and recessive models and nonparametric linkage analysis using the ‘all’ and ‘pairs’ statistics.</p

Average percentage of times (power) per model disease SNPs was under p-value thresholds when running MQLS on whole simulated pedigrees.

<p>Power ≥80% in bold.</p

Power to detect parametric HLOD and nonparametric LOD thresholds using PedCut followed by multipoint parametric linkage analyses assuming dominant and recessive models and nonparametric linkage analysis using the ‘all’ and ‘pairs’ statistics.

<p>All numbers are percentages.</p

Percentage of times (power) disease SNP crossed parametric HLOD or nonparametric LOD thresholds using PedCut followed by Merlin two-point parametric and nonparametric linkage analyses.

<p>1000 replicates of each disease model were performed. All numbers are percentages. Power >80% in bold.</p

Demographics of Amish Samples Used For Follow-up Genotyping.

<p>Percent female, age of exam and onset averages and standard deviations were calculated for the 921 samples which passed QC for follow-up genotyping.</p><p>Demographics of Amish Samples Used For Follow-up Genotyping.</p

MQLS-corrected allele frequencies and case-control association p-values for the top sequencing variants in the sequencing dataset.

<p>Chr = chromosome. MAF = minor allele frequency. Nucleotide position is based upon the UCSC hg19 human reference genome. Gene and Function annotated by SeattleSeq134.</p><p>MQLS-corrected allele frequencies and case-control association p-values for the top sequencing variants in the sequencing dataset.</p