Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals.
Mosaic sarbecovirus vaccination elicits cross-reactive responses in pre-immunized animals.
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花叶沙贝克病毒疫苗接种可在预免疫动物中引起交叉反应。
DOI：
10.1101/2024.02.08.576722
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Muramatsu,H
中科院分区：
文献类型：
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作者：
Cohen,AlexanderA;Keeffe,JenniferR;Schiepers,Ariën;Dross,SandraE;Greaney,AllisonJ;Rorick,AnnieV;Gao,Han;Gnanapragasam,PriyanthiNP;Fan,Chengcheng;WestJr,AnthonyP;Ramsingh,ArleneI;Erasmus,JesseH;Pata,JaniceD;Muramatsu,H
使用mosaic-8b（呈现8种SARS样β冠状病毒[sarbecovirus]受体结合域[RBD]的纳米颗粒）进行免疫比仅含有同型SARS-CoV-2 RBD的纳米颗粒更能引发更广泛的交叉反应抗体，并可预防sarbecovirus。为了研究原始抗原原罪（OAS）对马赛克-8b功效的影响，我们评估了非人类灵长类动物和小鼠先前接种的COVID-19疫苗对马赛克-8b、admix-8b（8种同型）或同型SARS-CoV-2免疫引起的抗sarbecovirus反应的影响，发现马赛克-8b的最大交叉反应性。分子命运图谱显示，来自特定 B 细胞群的抗体被差异化检测，由 WA1 刺突 mRNA-LNP 引发的 B 细胞在 RBD 纳米颗粒增强后主导了抗体反应。虽然马赛克 8b 和同型纳米颗粒增强了交叉反应抗体，但新生抗体主要由马赛克 8b 诱导，并且这些抗体对变异 RBD 具有特异性，与马赛克 8b 上的 RBD 具有更高的同一性。这些结果为美洲国家组织的机制提供了信息，并支持使用mosaic-8b来保护接种了COVID-19疫苗/感染的人类免受迄今为止未知的SARS-CoV-2变体和具有人类溢出潜力的动物SARS病毒的侵害。
Immunization with mosaic-8b (nanoparticles presenting 8 SARS-like betacoronavirus [sarbecovirus] receptor-binding domains [RBDs]) elicits more broadly cross-reactive antibodies than homotypic SARS-CoV-2 RBD-only nanoparticles and protects against sarbecoviruses. To investigate original antigenic sin (OAS) effects on mosaic-8b efficacy, we evaluated the effects of prior COVID-19 vaccinations in non-human primates and mice on anti-sarbecovirus responses elicited by mosaic-8b, admix-8b (8 homotypics), or homotypic SARS-CoV-2 immunizations, finding the greatest cross-reactivity for mosaic-8b. As demonstrated by molecular fate mapping, in which antibodies from specific cohorts of B cells are differentially detected, B cells primed by WA1 spike mRNA-LNP dominated antibody responses after RBD-nanoparticle boosting. While mosaic-8b- and homotypic-nanoparticles boosted cross-reactive antibodies,de novoantibodies were predominantly induced by mosaic-8b, and these were specific for variant RBDs with increased identity to RBDs on mosaic-8b. These results inform OAS mechanisms and support using mosaic-8b to protect COVID-19-vaccinated/infected humans against as-yet-unknown SARS-CoV-2 variants and animal sarbecoviruses with human spillover potential.