Repurposing NASVAC, a hepatitis B therapeutic vaccine, for pre- and postexposure prophylaxis of SARS-CoV-2 infection
Repurposing NASVAC, a hepatitis B therapeutic vaccine, for pre- and postexposure prophylaxis of SARS-CoV-2 infection
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DOI：
10.21203/rs.3.rs-438628/v1
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发表时间：
2021-04
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通讯作者：
S. M. Akbar;M. Mahtab;J. Aguilar;M. Uddin;Sakirul Khan;O. Yoshida;E. Pentón;Guillén . Gerardo;Y. Hiasa
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作者：
S. M. Akbar;M. Mahtab;J. Aguilar;M. Uddin;Sakirul Khan;O. Yoshida;E. Pentón;Guillén . Gerardo;Y. Hiasa
严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）和随后的2019冠状病毒（COVID-19）已导致全球数千万病例和数百万人死亡。尽管COVID-19出现已超过一年，但已报告更多疫情，并出现致命病毒的新变种。这种病毒似乎将在未来几年或几十年内继续感染人类，从而导致更多的疾病和死亡。去年在限制病毒传播方面的经验表明，一种或多种传统的遏制方法可能无效;此外，即使接种疫苗也不可能给社会带来免疫力。另一方面，使用能够从受感染宿主中根除SARS-CoV-2的药物消除病毒可能不是一个可实现的目标。基于这些现实，并在探索了病毒获得和COVID-19发病机制的潜在机制后，我们认为免疫治疗可能是遏制SARS-CoV-2的一个实际选择。在这项研究中，我们重新利用了一种免疫调节剂，其中含有两种B型肝炎病毒抗原，即B型肝炎表面抗原（HBsAg）和B型肝炎核心抗原（HBcAg）（称为NASVAC，古巴哈瓦那CIGB基因工程和生物技术中心），以了解其对SARS-CoV-2的作用。NASVAC在鼻腔给药后诱导了先天免疫细胞因子，并在两周的使用期间阻止了所有20名志愿者被诊断为SARS-CoV-2。四名志愿者在NASVAC给药结束后两周感染了SARS-CoV-2;其中三名志愿者几乎没有表现出任何症状，在没有任何干预的情况下康复，一名患有多种合并症的志愿者在医院接受了四天治疗，并完全康复。总之，对有SARS-CoV-2感染风险的受试者给予NASVAC是安全的。参与研究的受试者的细胞因子反应模式和无感染或轻度COVID-19感染是初步证据，表明该产品可以在SARS-CoV-2获得和/或复制的初始阶段预防或抑制SARS-CoV-2感染，值得进一步探索性试验，以确认NASVAC作为SARS-CoV背景下的前/后预防或先发制人治疗的能力。2感染。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent coronavirus 2019 (COVID-19) have led to tens of millions of cases and millions of deaths around the world. Although more than a year has passed since the emergence of COVID-19, more waves of the pandemic, with new variants of the deadly virus, have been reported. It seems that the virus will continue to infect people for years or decades to come and thus lead to more illnesses and deaths. The experiences last year regarding limiting the transmission of the virus indicate that one or more traditional methods of containment may not be effective; further, even vaccination may not give immunity to society. On the other hand, eliminating the virus using drugs capable of eradicating SARS-CoV-2 from the infected host may not be an achievable goal. Based on these realities and after exploring the mechanism underlying the acquisition of the virus and pathogenesis of COVID-19, we assumed that immune therapy may be a practical option for the containment of SARS-CoV-2. In this study, we repurposed an immune modulator containing two antigens of hepatitis B virus, hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (termed NASVAC, Center for Genetic Engineering and Biotechnology, CIGB, Havana, Cuba), to gain insight into its role against SARS-CoV-2. NASVAC induced cytokines of innate immunity following nasal administration and prevented all 20 volunteers from being diagnosed with SARS-CoV-2 during the two weeks of usage. Four volunteers were infected with SARS-CoV-2 two weeks after the end of NASVAC administration; three of them showed almost no symptoms and recovered without any intervention, and one with several comorbidities attended a hospital for four days and recovered completely. In conclusion, the administration of NASVAC to subjects at risk of SARS-CoV-2 infection was safe. The pattern of cytokine responses and absence of infection or mild COVID-19 infection of the subjects involved in the study are preliminary evidence indicating that this product may prevent or suppress SARS-CoV-2 infection at the initial stages of SARS-CoV-2 acquisition and/or replication and deserve further exploratory trials to confirm the capacity of NASVAC as pre/postexposure prophylaxis or pre-emptive therapy in the context of SARS-CoV-2 infection.