Department of Hepatitis and AIDS, Pasteur Institute of Iran, Tehran, Iran.
Amirabad Virology Laboratory, Vaccine Unit, Tehran, Iran.
Rev Med Virol. 2022 May;32(3):e2305. doi: 10.1002/rmv.2305. Epub 2021 Oct 26.
The development of effective and safe COVID-19 vaccines is a major move forward in our global effort to control the SARS-CoV-2 pandemic. The aims of this study were (1) to develop an inactivated whole-virus SARS-CoV-2 candidate vaccine named BIV1-CovIran and (2) to determine the safety and potency of BIV1-CovIran inactivated vaccine candidate against SARS-CoV-2. Infectious virus was isolated from nasopharyngeal swab specimen and propagated in Vero cells with clear cytopathic effects in a biosafety level-3 facility using the World Health Organization's laboratory biosafety guidance related to COVID-19. After characterisation of viral seed stocks, the virus working seed was scaled-up in Vero cells. After chemical inactivation and purification, it was formulated with alum adjuvant. Finally, different animal species were used to determine the toxicity and immunogenicity of the vaccine candidate. The study showed the safety profile in studied animals including guinea pig, rabbit, mice and monkeys. Immunisation at two different doses (3 or 5 μg per dose) elicited a high level of SARS-CoV-2 specific and neutralising antibodies in mice, rabbits and nonhuman primates. Rhesus macaques were immunised with the two-dose schedule of 5 or 3 μg of the BIV1-CovIran vaccine and showed highly efficient protection against 10 TCID50 of SARS-CoV-2 intratracheal challenge compared with the control group. These results highlight the BIV1-CovIran vaccine as a potential candidate to induce a strong and potent immune response that may be a promising and feasible vaccine to protect against SARS-CoV-2 infection.
开发有效和安全的 COVID-19 疫苗是我们全球努力控制 SARS-CoV-2 大流行的重要进展。本研究的目的是：（1）开发一种名为 BIV1-CovIran 的灭活全病毒 SARS-CoV-2 候选疫苗；（2）确定 BIV1-CovIran 灭活候选疫苗对 SARS-CoV-2 的安全性和效力。从鼻咽拭子标本中分离出传染性病毒，并在生物安全 3 级设施中的 Vero 细胞中用世界卫生组织关于 COVID-19 的实验室生物安全指南进行传代培养，出现明确的细胞病变效应。在对病毒种源进行鉴定后，将病毒工作种子在 Vero 细胞中进行扩大培养。化学灭活和纯化后，用铝佐剂进行配制。最后，使用不同的动物物种来确定候选疫苗的毒性和免疫原性。研究表明，候选疫苗在包括豚鼠、兔、鼠和猴在内的研究动物中具有良好的安全性。在两个不同剂量（每个剂量 3 或 5μg）下免疫，可在小鼠、兔和非人灵长类动物中引起高水平的 SARS-CoV-2 特异性和中和抗体。恒河猴用 BIV1-CovIran 疫苗的两剂量方案（5 或 3μg）免疫，与对照组相比，对 10 TCID50 的 SARS-CoV-2 气管内攻击显示出高度有效的保护作用。这些结果突出了 BIV1-CovIran 疫苗作为一种有潜力的候选疫苗，可以诱导强烈和有效的免疫反应，可能是一种有前途和可行的疫苗，可预防 SARS-CoV-2 感染。
