英国Andrew Macadam等研究人员合作揭示脊髓灰质炎病毒1型和3型减毒口服疫苗的遗传稳定化。2023年6月14日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员表示，使用Sabin口服小儿麻痹症减毒活疫苗（OPV）进行接种，可产生强大的肠道和体液免疫力，是控制小儿麻痹症的关键。与任何RNA病毒一样，OPV也会迅速演化，失去对重新获得毒力至关重要的减毒决定因素，从而产生疫苗衍生的、毒性脊髓灰质炎病毒变体。这些变体在免疫力低下的人群中传播，导致传播的、疫苗衍生的脊髓灰质炎病毒进一步演化，并具有更高的传播能力，这是脊髓灰质炎重新出现的重大风险。一种新的2型OPV（nOPV2）在遗传稳定性和免疫原性方面具有良好的临床数据，最近获得了世界卫生组织的授权，可用于应对传播性、疫苗衍生的脊髓灰质炎病毒爆发的情况。

研究人员报告了另外两种针对1型和3型脊髓灰质炎病毒的候选减毒活疫苗的开发。这些候选疫苗是通过用Sabin 1或3型的编码区替换nOPV2的编码区产生的。这些嵌合病毒显示出与nOPV2相似的生长表型，免疫原性与它们的亲本Sabin毒株相当，但减毒程度更高。研究人员在小鼠身上的实验和深度测序分析证实，这些候选病毒仍然是减毒的，并保留了所有记录在案的关于加速病毒演化后的遗传稳定性nOPV2特征。重要的是，这些候选疫苗作为单价和多价制剂在小鼠体内具有很高的免疫原性，可能有助于根除脊髓灰质炎病毒。

附：英文原文

Title: Genetic stabilization of attenuated oral vaccines against poliovirus types 1 and 3

Author: Yeh, Ming Te, Smith, Matthew, Carlyle, Sarah, Konopka-Anstadt, Jennifer L., Burns, Cara C., Konz, John, Andino, Raul, Macadam, Andrew

Issue&Volume: 2023-06-14

Abstract: Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence1,2,3 resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.

DOI: 10.1038/s41586-023-06212-3

Source: https://www.nature.com/articles/s41586-023-06212-3