Pre-clinical Vaccine and Antibody Development for Coronavirus Disease 2019 (COVID-19)

2019 年冠状病毒病 (COVID-19) 的临床前疫苗和抗体开发

• 批准号: 10712584
• 负责人: Richard A Koup
• 金额: $ 28.54万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10712584
• 关键词: 2019-nCoV; Antibodies; Antibody Response; Antigen Targeting; Antigens; COVID-19; COVID-19 patient; Data; Development; Disease Outbreaks; Emergency Situation; Future; Genes; Genetic; Hepatitis B Surface Antigens; Human; Immune response; Immunization; Laboratories; Moderna COVID-19 vaccine; Mucous Membrane; Mus; National Institute of Allergy and Infectious Disease; Production; Proteins; RNA vaccine; SARS-CoV-2 immunity; SARS-CoV-2 infection; Surface; Testing; Vaccinee; Vaccines; Virus-like particle; antigen test; base; design; genetic vaccine; improved; lumazine; nanoparticle; neutralizing antibody; next generation; pandemic disease; pre-clinical; prevent; self assembly; vaccine candidate; vaccine-induced antibodies; virology

Since there is no effective cure for COVID-19. Though the mRNA vaccines were authorized for emergency use, the durability of protection provided by these two mRNA vaccines is still a concern, given the fact that the spike-specific antibodies decline rapidly in convalescent sera of COVID patients. During the past years, the Virology Laboratory has collaborated with other intramural NIAID labs and other external collaborators to develop a more effective and long-lasting vaccine for controlling the ongoing pandemic and for preventing future outbreaks. For the past last year, we are testing various new designs of non-infectious self-assembly Virus-Like-Particle (VLP) expressing the SARS-CoV-2 spike on the nanoparticles' surface as a potential improved vaccine which may elicit stronger and prolong immune responses. We are testing two concepts, first one is to see if we can express and produce VLPs with target antigens on the VLP surface, the second one is to use gene-base vaccine approach for delivering the modified VLP gene directly in order to avoid the common problems involving the production of the modified VLPs immunogens. We first assessed whether hepatitis B surface antigen (HBsAg)-based nanoparticles and also lumazine synthase nanoparticles with SARS-CoV-2 spike can elicit potent and long lasting immunity against SARS-CoV-2 in mice . The data showed that genetic delivery of SARS-CoV-2 S6P-HBsAg and also on lumazine synthase nanoparticles can both elicit potent and durable neutralizing antibody (nAb) responses. S6P-HBsAgs can elicit substantially more potent nAb responses than S2P matching mRNA-1273 in mice. Our findings highlight the potential of S6P-HBsAgs as next generation genetic vaccine candidates against SARS-CoV-2. Furthermore, we are testing antigen protein mucosal boosting after the initial gene-based prime immunization would elicit improved immune responses or not.

因为新冠肺炎没有有效的治疗方法。尽管信使核糖核酸疫苗被授权紧急使用，但这两种信使核糖核酸疫苗提供的保护的持久性仍然是一个令人担忧的问题，因为在COVID患者的恢复期血清中，尖峰特异性抗体迅速下降。在过去的几年里，病毒学实验室与NIAID的其他内部实验室和其他外部合作者合作，开发了一种更有效和更持久的疫苗，以控制正在进行的大流行和预防未来的暴发。 在过去的一年里，我们正在测试各种新的非传染性自组装病毒样颗粒(VLP)，这种颗粒在纳米颗粒表面表达SARS-CoV-2尖峰，作为一种潜在的改进疫苗，可能会引发更强的和延长免疫反应。我们正在测试两个概念，一是看我们能否在VLP表面表达和生产带有靶抗原的VLP，二是利用基因疫苗的方法直接传递修饰的VLP基因，以避免常见的涉及到修饰的VLP免疫原生产的问题。我们首先评估了基于乙肝表面抗原(HBs)的纳米颗粒和带有SARS-CoV-2尖峰的鲁马津合成酶纳米颗粒是否可以在小鼠中诱导针对SARS-CoV-2的有效和持久的免疫。结果表明，SARS-CoV-2、S6P-HBs和鲁马津合成酶纳米粒的基因传递均可诱导有效而持久的中和抗体(NAB)应答。与S2P匹配的mRNA-1273相比，S6P-HBs Ags可以在小鼠中诱导更强的NAB反应。我们的发现突出了S6P-HBsAgs作为针对SARS-CoV-2的下一代基因疫苗候选的潜力。此外，我们正在测试最初的基于基因的初级免疫后的抗原蛋白粘膜增强是否会引起更好的免疫反应。