King Hannah A D, Gordon Joyce M, Naouar Ines Elakhal, Ahmed Aslaa, Cincotta Camila Macedo, Subra Caroline, Peachman Kristina K, Hack Holly H, Chen Rita E, Thomas Paul V, Chen Wei-Hung, Sankhala Rajeshwer S, Hajduczki Agnes, Martinez Elizabeth J, Peterson Caroline E, Chang William C, Choe Misook, Smith Clayton, Headley Jarrett A, Elyard Hanne A, Cook Anthony, Anderson Alexander, Wuertz Kathryn McGuckin, Dong Ming, Swafford Isabella, Case James B, Currier Jeffrey R, Lal Kerri G, Amare Mihret F, Dussupt Vincent, Molnar Sebastian, Daye Sharon P, Zeng Xiankun, Barkei Erica K, Alfson Kendra, Staples Hilary M, Carrion Ricardo, Krebs Shelly J, Paquin-Proulx Dominic, Karasavvas Nicos, Polonis Victoria R, Jagodzinski Linda L, Vasan Sandhya, Scott Paul T, Huang Yaoxing, Nair Manoj S, Ho David D, de Val Natalia, Diamond Michael S, Lewis Mark G, Rao Mangala, Matyas Gary R, Gromowski Gregory D, Peel Sheila A, Michael Nelson L, Modjarrad Kayvon, Bolton Diane L
bioRxiv. 2021 Apr 10:2021.04.09.439166. doi: 10.1101/2021.04.09.439166.
Emergence of novel variants of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) underscores the need for next-generation vaccines able to elicit broad and durable immunity. Here we report the evaluation of a ferritin nanoparticle vaccine displaying the receptor-binding domain of the SARS-CoV-2 spike protein (RFN) adjuvanted with Army Liposomal Formulation QS-21 (ALFQ). RFN vaccination of macaques using a two-dose regimen resulted in robust, predominantly Th1 CD4+ T cell responses and reciprocal peak mean neutralizing antibody titers of 14,000-21,000. Rapid control of viral replication was achieved in the upper and lower airways of animals after high-dose SARS-CoV-2 respiratory challenge, with undetectable replication within four days in 7 of 8 animals receiving 50 µg RFN. Cross-neutralization activity against SARS-CoV-2 variant B.1.351 decreased only ∼2-fold relative to USA-WA1. In addition, neutralizing, effector antibody and cellular responses targeted the heterotypic SARS-CoV-1, highlighting the broad immunogenicity of RFN-ALFQ for SARS-like betacoronavirus vaccine development.
The emergence of SARS-CoV-2 variants of concern (VOC) that reduce the efficacy of current COVID-19 vaccines is a major threat to pandemic control. We evaluate a SARS-CoV-2 Spike receptor-binding domain ferritin nanoparticle protein vaccine (RFN) in a nonhuman primate challenge model that addresses the need for a next-generation, efficacious vaccine with increased pan-SARS breadth of coverage. RFN, adjuvanted with a liposomal-QS21 formulation (ALFQ), elicits humoral and cellular immune responses exceeding those of current vaccines in terms of breadth and potency and protects against high-dose respiratory tract challenge. Neutralization activity against the B.1.351 VOC within two-fold of wild-type virus and against SARS-CoV-1 indicate exceptional breadth. Our results support consideration of RFN for SARS-like betacoronavirus vaccine development.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）新型变体的出现凸显了对能够引发广泛且持久免疫力的下一代疫苗的需求。在此，我们报告了一种展示SARS-CoV-2刺突蛋白受体结合域的铁蛋白纳米颗粒疫苗（RFN）与陆军脂质体制剂QS-21（ALFQ）联合使用的评估情况。使用两剂方案对猕猴进行RFN疫苗接种可产生强烈的、主要为Th1型的CD4 + T细胞反应，相互对应的峰值平均中和抗体滴度为14,000 - 21,000。在高剂量SARS-CoV-2呼吸道攻击后，动物的上、下呼吸道实现了病毒复制的快速控制，在接受50μg RFN的8只动物中，有7只在四天内病毒复制检测不到。相对于USA-WA1，对SARS-CoV-2变体B.1.351的交叉中和活性仅下降约2倍。此外，中和、效应抗体和细胞反应靶向异型SARS-CoV-1，突出了RFN-ALFQ在SARS样β冠状病毒疫苗开发方面的广泛免疫原性。
令人担忧的SARS-CoV-2变体（VOC）的出现降低了当前COVID-19疫苗的效力，这是对大流行控制的重大威胁。我们在非人灵长类动物攻击模型中评估了一种SARS-CoV-2刺突受体结合域铁蛋白纳米颗粒蛋白疫苗（RFN），该模型满足了对具有更广泛的泛SARS覆盖范围的下一代有效疫苗的需求。与脂质体-QS21制剂（ALFQ）联合使用的RFN引发的体液和细胞免疫反应在广度和效力方面超过了当前疫苗，并能抵御高剂量呼吸道攻击。对B.1.351 VOC的中和活性在野生型病毒的两倍以内，对SARS-CoV-1的中和活性表明其具有卓越的广度。我们的结果支持将RFN用于SARS样β冠状病毒疫苗的开发。
