A highly immunogenic UVC inactivated Sabin based polio vaccine.

IF 6.9 1区 医学 Q1 IMMUNOLOGY NPJ Vaccines Pub Date : 2024-11-14 DOI:10.1038/s41541-024-00995-w
Gregory J Tobin, John K Tobin, Taralyn J Wiggins, Ruth V Bushnell, Arina V Kozar, Matthew F Maale, David A MacLeod, Heather N Meeks, Michael J Daly, Stephen J Dollery
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Abstract

Despite their efficacy, the currently available polio vaccines, oral polio vaccine (OPV) and inactivated polio vaccine (IPV), possess inherent flaws posing significant challenges in the global eradication of polio. OPV, which uses live Sabin attenuated strains, carries the risk of reversion to pathogenic forms and causing vaccine-associated paralytic poliomyelitis (VAPP) and vaccine-derived polio disease (VDPD) in incompletely vaccinated or immune-compromised individuals. Conventional IPVs, which are non-replicative, are more expensive to manufacture and introduce biohazard and biosecurity risks due to the use of neuropathogenic strains in production. These types of limitations have led to a call by the Global Polio Eradication Initiative and others for the development of updated polio vaccines. We are developing a novel Ultraviolet-C radiation (UVC) inactivation method that preserves immunogenicity and is compatible with attenuated strains of polio. The method incorporates an antioxidant complex, manganese-decapeptide-phosphate (MDP), derived from the radioresistant bacterium Deinococcus radiodurans. The inclusion of MDP protects the immunogenic neutralizing epitopes from damage during UVC inactivation. The novel vaccine candidate, ultraIPVTM, produced using these methods demonstrates three crucial attributes: complete inactivation, which precludes the risk of vaccine-associated disease; use of non-pathogenic strains to reduce production risks; and significantly enhanced yield of doses per milligram of input virus, which could increase vaccine supply while reducing costs. Additionally, ultraIPVTM retains antigenicity post-freeze-thaw cycles, a testament to its robustness.

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基于 Sabin 的高免疫原性紫外线灭活脊髓灰质炎疫苗。
尽管目前可用的脊髓灰质炎疫苗(口服脊髓灰质炎疫苗 (OPV) 和脊髓灰质炎灭活疫苗 (IPV))具有功效,但它们也存在固有的缺陷,给全球根除脊髓灰质炎带来了重大挑战。口服脊髓灰质炎疫苗(OPV)使用的是 Sabin 减毒活疫苗株,存在返祖致病的风险,会导致未完全接种疫苗或免疫力低下的人患上疫苗相关性麻痹性脊髓灰质炎(VAPP)和疫苗衍生脊髓灰质炎疾病(VDPD)。传统 IPV 是非复制型疫苗,生产成本较高,而且由于在生产过程中使用了神经致病株,因此存在生物危害和生物安全风险。这些限制因素促使全球根除脊髓灰质炎倡议和其他组织呼吁开发更新的脊髓灰质炎疫苗。我们正在开发一种新型紫外线-C 辐射(UVC)灭活方法,这种方法既能保持免疫原性,又能与脊髓灰质炎减毒株兼容。该方法采用了一种抗氧化剂复合物--锰-十肽-磷酸(MDP),这种复合物来源于抗放射细菌--放射性碘化球菌(Deinococcus radiodurans)。MDP 的加入可保护免疫原性中和表位免受紫外线灭活过程中的破坏。使用这些方法生产的新型候选疫苗 ultraIPVTM 具有三个关键特性:完全灭活,排除了疫苗相关疾病的风险;使用非致病性菌株,降低生产风险;每毫克输入病毒的剂量产量显著提高,可在降低成本的同时增加疫苗供应量。此外,ultraIPVTM 在冻融循环后仍能保持抗原性,这证明了它的稳定性。
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来源期刊
NPJ Vaccines
NPJ Vaccines Immunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍: Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.
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