Nanishi Etsuro, Borriello Francesco, Seo Hyuk-Soo, O'Meara Timothy R, McGrath Marisa E, Saito Yoshine, Chen Jing, Diray-Arce Joann, Song Kijun, Xu Andrew Z, Barman Soumik, Menon Manisha, Dong Danica, Caradonna Timothy M, Feldman Jared, Hauser Blake M, Schmidt Aaron G, Baden Lindsey R, Ernst Robert K, Dillen Carly, Yu Jingyou, Chang Aiquan, Hilgers Luuk, Platenburg Peter Paul, Dhe-Paganon Sirano, Barouch Dan H, Ozonoff Al, Zanoni Ivan, Frieman Matthew B, Dowling David J, Levy Ofer
Precision Vaccines Program, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
NPJ Vaccines. 2023 Feb 14;8(1):18. doi: 10.1038/s41541-023-00610-4.
Development of SARS-CoV-2 vaccines that protect vulnerable populations is a public health priority. Here, we took a systematic and iterative approach by testing several adjuvants and SARS-CoV-2 antigens to identify a combination that elicits antibodies and protection in young and aged mice. While demonstrating superior immunogenicity to soluble receptor-binding domain (RBD), RBD displayed as a protein nanoparticle (RBD-NP) generated limited antibody responses. Comparison of multiple adjuvants including AddaVax, AddaS03, and AS01B in young and aged mice demonstrated that an oil-in-water emulsion containing carbohydrate fatty acid monosulphate derivative (CMS:O/W) most effectively enhanced RBD-NP-induced cross-neutralizing antibodies and protection across age groups. CMS:O/W enhanced antigen retention in the draining lymph node, induced injection site, and lymph node cytokines, with CMS inducing MyD88-dependent Th1 cytokine polarization. Furthermore, CMS and O/W synergistically induced chemokine production from human PBMCs. Overall, CMS:O/W adjuvant may enhance immunogenicity and protection of vulnerable populations against SARS-CoV-2 and other infectious pathogens.
开发能保护弱势群体的新冠病毒疫苗是一项公共卫生优先事项。在此,我们采用了一种系统且迭代的方法,通过测试多种佐剂和新冠病毒抗原,以确定一种能在年轻和老年小鼠中引发抗体并提供保护的组合。虽然与可溶性受体结合结构域(RBD)相比,作为蛋白质纳米颗粒展示的RBD(RBD-NP)表现出更高的免疫原性,但它引发的抗体反应有限。在年轻和老年小鼠中对包括AddaVax、AddaS03和AS01B在内的多种佐剂进行比较后发现,一种含有碳水化合物脂肪酸单硫酸盐衍生物的水包油乳液(CMS:O/W)能最有效地增强RBD-NP诱导的跨年龄组交叉中和抗体及保护作用。CMS:O/W增强了引流淋巴结、注射部位和淋巴结细胞因子中的抗原保留,其中CMS诱导依赖MyD88的Th1细胞因子极化。此外,CMS和O/W协同诱导人外周血单个核细胞产生趋化因子。总体而言,CMS:O/W佐剂可能增强弱势群体对新冠病毒和其他传染性病原体的免疫原性及保护作用。