Atochina-Vasserman Elena N, Lindesmith Lisa C, Mirabelli Carmen, Ona Nathan A, Reagan Erin K, Brewer-Jensen Paul D, Mercado-Lopez Xiomara, Shahnawaz Hamna, Meshanni Jaclynn A, Baboo Ishana, Mallory Michael L, Zweigart Mark R, May Samantha R, Mui Barbara L, Tam Ying K, Wobus Christiane E, Baric Ralph S, Weissman Drew
Institue for RNA Innovation, the University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
NPJ Vaccines. 2024 Oct 1;9(1):182. doi: 10.1038/s41541-024-00976-z.
Nucleoside-modified mRNA-LNP vaccines have revolutionized vaccine development against infectious pathogens due to their ability to elicit potent humoral and cellular immune responses. In this article, we present the results of the first norovirus vaccine candidate employing mRNA-LNP platform technology. The mRNA-LNP bivalent vaccine encoding the major capsid protein VP1 from GI.1 and GII.4 of human norovirus, generated high levels of neutralizing antibodies, robust cellular responses, and effectively protected human enteroids from infection by the most prevalent genotype (GII.4). These results serve as a proof of concept, demonstrating that a modified-nucleoside mRNA-LNP vaccine based on norovirus VP1 sequences can stimulate an immunogenic response in vivo and generates neutralizing antibodies capable of preventing viral infection in models of human gastrointestinal tract infection.
核苷修饰的mRNA-LNP疫苗因其能够引发强大的体液免疫和细胞免疫反应，彻底改变了针对传染性病原体的疫苗开发。在本文中，我们展示了首个采用mRNA-LNP平台技术的诺如病毒候选疫苗的结果。编码人诺如病毒GI.1和GII.4主要衣壳蛋白VP1的mRNA-LNP二价疫苗，产生了高水平的中和抗体、强大的细胞反应，并有效保护人肠上皮细胞免受最流行基因型（GII.4）的感染。这些结果作为概念验证，表明基于诺如病毒VP1序列的修饰核苷mRNA-LNP疫苗能够在体内刺激免疫原性反应，并产生能够在人类胃肠道感染模型中预防病毒感染的中和抗体。
