Abstract
AbstractFollowing the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using Pichia pastoris, however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally-stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using Pichia pastoris. We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly-expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.
Publisher
Cold Spring Harbor Laboratory
Reference65 articles.
1. Polio Now – GPEI.
2. Zambon M , Martin J. 2018. Polio eradication: next steps and future challenges. Eurosurveillance 23.
3. Two out of three wild poliovirus strains eradicated.
4. Polio vaccination: past, present and future
5. Response to a wild poliovirus type 2 (WPV2)-shedding event following accidental exposure to WPV2, the Netherlands, April 2017;Eurosurveillance,2017
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献