There is an urgent requirement for safe and effective vaccines to prevent novel coronavirus disease (COVID-19) caused by SARS-CoV-2. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferret and rhesus macaques challenged with SARS-CoV-2 to assess the potential for VED in animals vaccinated with formaldehyde-inactivated SARS-CoV-2 (FIV) formulated with Alhydrogel, compared to a negative control vaccine in ferrets or unvaccinated macaques. We showed no evidence of enhanced disease in ferrets or rhesus macaques given FIV except for mild transient enhanced disease seen at seven days post infection in ferrets. This increased lung pathology was observed early in the infection (day 7) but was resolved by day 15. We also demonstrate that formaldehyde treatment of SARS-CoV-2 reduces exposure of the spike receptor binding domain providing a mechanistic explanation for suboptimal immunity.

中文翻译：

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对雪貂和恒河猴进行福尔马林灭活疫苗免疫后，SARS-CoV-2攻击的免疫和病理结果

迫切需要安全有效的疫苗，以预防由SARS-CoV-2引起的新型冠状病毒疾病（COVID-19）。开发新的病毒疫苗所关注的是诱导疫苗增强疾病（VED）的潜力。在几项针对SARS-CoV-1和MERS疫苗的临床前研究中均报道了这一现象，但在SARS-CoV-2疫苗中未见报道。我们已经用SARS-CoV-2攻击的雪貂和恒河猴来评估用Alhydrogel配制的甲醛灭活SARS-CoV-2（FIV）疫苗接种的动物中VED的潜力，与雪貂或未接种猕猴的阴性对照疫苗相比。我们没有显示出给予FIV的雪貂或恒河猴增强疾病的证据，除了在雪貂感染后7天出现的轻度短暂性疾病增强。