Joyce Michael G, King Hannah A D, Naouar Ines Elakhal, Ahmed Aslaa, Peachman Kristina K, Cincotta Camila Macedo, Subra Caroline, 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, Lee Parker J, Headley Jarrett A, Taddese Mekdi G, Elyard Hanne A, Cook Anthony, Anderson Alexander, McGuckin-Wuertz Kathryn, Dong Ming, Swafford Isabella, Case James B, Currier Jeffrey R, Lal Kerri G, O'Connell Robert J, Molnar Sebastian, Nair Manoj S, Dussupt Vincent, Daye Sharon P, Zeng Xiankun, Barkei Erica K, Staples Hilary M, Alfson Kendra, Carrion Ricardo, Krebs Shelly J, Paquin-Proulx Dominic, Karasavva Nicos, Polonis Victoria R, Jagodzinski Linda L, Amare Mihret F, Vasan Sandhya, Scott Paul T, Huang Yaoxing, 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, Bolton Diane L, Modjarrad Kayvon
bioRxiv. 2021 Mar 25:2021.03.24.436523. doi: 10.1101/2021.03.24.436523.
The emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019 (COVID-19). We developed and evaluated an adjuvanted SARS-CoV-2 Spike Ferritin Nanoparticle (SpFN) vaccine in nonhuman primates (NHPs). High-dose (50 g) SpFN vaccine, given twice within a 28 day interval, induced a Th1-biased CD4 T cell helper response and a peak neutralizing antibody geometric mean titer of 52,773 against wild-type virus, with activity against SARS-CoV-1 and minimal decrement against variants of concern. Vaccinated animals mounted an anamnestic response upon high-dose SARS-CoV-2 respiratory challenge that translated into rapid elimination of replicating virus in their upper and lower airways and lung parenchyma. SpFN's potent and broad immunogenicity profile and resulting efficacy in NHPs supports its utility as a candidate platform for SARS-like betacoronaviruses.
ONE-SENTENCE SUMMARY: A SARS-CoV-2 Spike protein ferritin nanoparticle vaccine, co-formulated with a liposomal adjuvant, elicits broad neutralizing antibody responses that exceed those observed for other major vaccines and rapidly protects against respiratory infection and disease in the upper and lower airways and lung tissue of nonhuman primates.
新型严重急性呼吸综合征冠状病毒2（SARS-CoV-2）变体的出现凸显了对能提供针对2019冠状病毒病（COVID-19）广泛保护的下一代疫苗的持续需求。我们在非人类灵长类动物（NHP）中开发并评估了一种佐剂化的SARS-CoV-2刺突铁蛋白纳米颗粒（SpFN）疫苗。高剂量（50微克）的SpFN疫苗在28天间隔内接种两次，诱导了以Th1为主的CD4 T细胞辅助反应，针对野生型病毒的中和抗体几何平均滴度峰值为52773，对SARS-CoV-1有活性，对关注的变体的活性降低最小。接种疫苗的动物在高剂量SARS-CoV-2呼吸道攻击后产生了回忆反应，这转化为其上下呼吸道和肺实质中复制病毒的快速清除。SpFN强大而广泛的免疫原性特征及其在NHP中的有效性支持其作为类SARSβ冠状病毒候选平台的实用性。
一种与脂质体佐剂共同配制的SARS-CoV-2刺突蛋白铁蛋白纳米颗粒疫苗引发了广泛的中和抗体反应，超过了其他主要疫苗所观察到的反应，并能迅速保护非人类灵长类动物的上下呼吸道和肺组织免受呼吸道感染和疾病。
