Li Dapeng, Martinez David R, Schäfer Alexandra, Chen Haiyan, Barr Maggie, Sutherland Laura L, Lee Esther, Parks Robert, Mielke Dieter, Edwards Whitney, Newman Amanda, Bock Kevin W, Minai Mahnaz, Nagata Bianca M, Gagne Matthew, Douek Daniel C, DeMarco C Todd, Denny Thomas N, Oguin Thomas H, Brown Alecia, Rountree Wes, Wang Yunfei, Mansouri Katayoun, Edwards Robert J, Ferrari Guido, Sempowski Gregory D, Eaton Amanda, Tang Juanjie, Cain Derek W, Santra Sampa, Pardi Norbert, Weissman Drew, Tomai Mark A, Fox Christopher B, Moore Ian N, Andersen Hanne, Lewis Mark G, Golding Hana, Seder Robert, Khurana Surender, Baric Ralph S, Montefiori David C, Saunders Kevin O, Haynes Barton F
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
bioRxiv. 2022 Feb 14:2022.01.26.477915. doi: 10.1101/2022.01.26.477915.
Coronavirus vaccines that are highly effective against SARS-CoV-2 variants are needed to control the current pandemic. We previously reported a receptor-binding domain (RBD) sortase A-conjugated ferritin nanoparticle (RBD-scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected monkeys from SARS-CoV-2 WA-1 infection. Here, we demonstrate SARS-CoV-2 RBD-scNP immunization induces potent neutralizing antibodies in non-human primates (NHPs) against all eight SARS-CoV-2 variants tested including the Beta, Delta, and Omicron variants. The Omicron variant was neutralized by RBD-scNP-induced serum antibodies with a mean of 10.6-fold reduction of ID50 titers compared to SARS-CoV-2 D614G. Immunization with RBD-scNPs protected NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protected mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect NHPs and mice from multiple different SARS-related viruses. Such a vaccine could provide the needed immunity to slow the spread of and reduce disease caused by SARS-CoV-2 variants such as Delta and Omicron.
需要高效对抗严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的冠状病毒疫苗来控制当前的大流行。我们之前报道了一种受体结合域（RBD）分选酶A缀合的铁蛋白纳米颗粒（RBD-scNP）疫苗，该疫苗可诱导针对SARS-CoV-2和新出现的乙型冠状病毒属病毒的中和抗体，并保护猴子免受SARS-CoV-2 WA-1感染。在此，我们证明SARS-CoV-2 RBD-scNP免疫在非人灵长类动物（NHP）中诱导产生针对所有八种测试的SARS-CoV-2变体（包括贝塔、德尔塔和奥密克戎变体）的强效中和抗体。与SARS-CoV-2 D614G相比，奥密克戎变体被RBD-scNP诱导的血清抗体中和，ID50滴度平均降低10.6倍。用RBD-scNP免疫可保护NHP免受SARS-CoV-2 WA-1、贝塔和德尔塔变体的攻击，并保护小鼠免受SARS-CoV-2贝塔变体和其他两种异源乙型冠状病毒属病毒的攻击。这些结果证明了RBD-scNP诱导对SARS-CoV-2变体广泛中和以及保护NHP和小鼠免受多种不同SARS相关病毒攻击的能力。这样一种疫苗可以提供所需的免疫力，以减缓德尔塔和奥密克戎等SARS-CoV-2变体的传播并减少其所致疾病。
