Immunological and pathological outcomes of SARS-CoV-2 challenge after formalin-inactivated vaccine immunisation of ferrets and rhesus macaques
Immunological and pathological outcomes of SARS-CoV-2 challenge after formalin-inactivated vaccine immunisation of ferrets and rhesus macaques
复制标题
雪貂和恒河猴福尔马林灭活疫苗免疫后 SARS-CoV-2 攻击的免疫学和病理学结果
DOI：
10.1101/2020.12.21.423746
复制
发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Bewley K
中科院分区：
文献类型：
--
作者：
Bewley K
目前迫切需要安全有效的疫苗来预防由SARS-CoV-2引起的新型冠状病毒病（COVID-19）。开发新病毒疫苗的一个问题是诱导疫苗增强疾病（VED）的可能性。在SARS-CoV-1和MERS疫苗的几项临床前研究中报告了这一点，但尚未报告SARS-CoV-2疫苗。我们使用了用SARS-CoV-2攻击的雪貂和恒河猴，以评估与雪貂或未接种疫苗的恒河猴中的阴性对照疫苗相比，用Alhydrogel配制的去甲氨蝶呤灭活的SARS-CoV-2（FIV）疫苗接种的动物中VED的可能性。我们没有发现雪貂或恒河猴感染FIV后疾病增强的证据，除了雪貂感染后7天出现轻度一过性疾病增强。在感染早期（第7天）观察到这种增加的肺部病理学，但在第15天消退。我们还表明，甲醛处理的SARS-CoV-2减少暴露的刺突受体结合域提供了一个机制解释次优免疫。
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.
登录
查看更多内容
ABSL-3 实验室灵活的成像方法
影响因子：
1.5
作者：
M. Dennis;S. Parks;Gordon Bell;Irene Taylor;J. Lakeman;S. Sharpe
通讯作者：
S. Sharpe
影响因子：
11.4
作者：
Caly, Leon;Druce, Julian;Catton, Mike G.
通讯作者：
Catton, Mike G.
影响因子：
64.5
作者：
Meckiff BJ;Ramírez-Suástegui C;Fajardo V;Chee SJ;Kusnadi A;Simon H;Eschweiler S;Grifoni A;Pelosi E;Weiskopf D;Sette A;Ay F;Seumois G;Ottensmeier CH;Vijayanand P
通讯作者：
Vijayanand P
DOI：
10.1016/s0140-6736(20)32466-1
发表时间：
2021-12-19
期刊：
Lancet (London, England)
影响因子：
--
作者：
Ramasamy MN;Minassian AM;Ewer KJ;Flaxman AL;Folegatti PM;Owens DR;Voysey M;Aley PK;Angus B;Babbage G;Belij-Rammerstorfer S;Berry L;Bibi S;Bittaye M;Cathie K;Chappell H;Charlton S;Cicconi P;Clutterbuck EA;Colin-Jones R;Dold C;Emary KRW;Fedosyuk S;Fuskova M;Gbesemete D;Green C;Hallis B;Hou MM;Jenkin D;Joe CCD;Kelly EJ;Kerridge S;Lawrie AM;Lelliott A;Lwin MN;Makinson R;Marchevsky NG;Mujadidi Y;Munro APS;Pacurar M;Plested E;Rand J;Rawlinson T;Rhead S;Robinson H;Ritchie AJ;Ross-Russell AL;Saich S;Singh N;Smith CC;Snape MD;Song R;Tarrant R;Themistocleous Y;Thomas KM;Villafana TL;Warren SC;Watson MEE;Douglas AD;Hill AVS;Lambe T;Gilbert SC;Faust SN;Pollard AJ;Oxford COVID Vaccine Trial Group
通讯作者：
Oxford COVID Vaccine Trial Group
影响因子：
--
作者：
Kruse, Robert L
通讯作者：
Kruse, Robert L