Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate.
Nonhuman primate to human immunobridging to infer the protective effect of an Ebola virus vaccine candidate.
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非人类的灵长类动物对人类免疫三体，以推断埃博拉病毒疫苗候选者的保护作用。
DOI：
10.1038/s41541-020-00261-9
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发表时间：
2020-12-17
期刊：
影响因子：
9.2
通讯作者：
Callendret B
中科院分区：
文献类型：
--
作者：
Roozendaal R;Hendriks J;van Effelterre T;Spiessens B;Dekking L;Solforosi L;Czapska-Casey D;Bockstal V;Stoop J;Splinter D;Janssen S;Baelen BV;Verbruggen N;Serroyen J;Dekeyster E;Volkmann A;Wollmann Y;Carrion R Jr;Giavedoni LD;Robinson C;Leyssen M;Douoguih M;Luhn K;Pau MG;Sadoff J;Vandebosch A;Schuitemaker H;Zahn R;Callendret B
事实证明，对埃博拉病毒（EBOV）疫苗进行传统的有效性试验具有挑战性。在缺乏有效性数据的情况下，免疫桥接是一种推断疫苗保护作用可能性的方法，通过使用疫苗免疫原性与适当动物模型中预期结果之间的关系，将人体中的疫苗免疫原性转化为保护作用。我们在此建议通过免疫印迹法推断Ad26.ZEBOV、MVA-BN-Filo疫苗方案在人类中间隔8周的保护作用。在食蟹猴（非人灵长类动物[NHP]）中使用完全致死EBOV Kikwit攻击模型获得Ad26.ZEBOV和MVA-BN-Filo疫苗方案的免疫原性和保护效力数据。通过逻辑回归分析评估EBOV中和抗体、糖蛋白（GP）结合抗体和GP反应性T细胞与NHP患者存活率之间的相关性。针对EBOV表面GP的结合抗体被鉴定为与EBOV攻击后的存活具有最强相关性的免疫参数，并且用于使用来自I期研究的公开数据来推断疫苗在人中的预测保护作用。人疫苗引发的EBOV GP结合抗体水平在与NHP中针对死亡率的显著保护相关的范围内。基于该免疫桥接分析，由Ad26.ZEBOV、MVA-BN-Filo疫苗方案在人中引发的EBOV GP特异性结合抗体水平将可能提供针对EBOV疾病的保护。
It has been proven challenging to conduct traditional efficacy trials for Ebola virus (EBOV) vaccines. In the absence of efficacy data, immunobridging is an approach to infer the likelihood of a vaccine protective effect, by translating vaccine immunogenicity in humans to a protective effect, using the relationship between vaccine immunogenicity and the desired outcome in a suitable animal model. We here propose to infer the protective effect of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen with an 8-week interval in humans by immunobridging. Immunogenicity and protective efficacy data were obtained for Ad26.ZEBOV and MVA-BN-Filo vaccine regimens using a fully lethal EBOV Kikwit challenge model in cynomolgus monkeys (nonhuman primates [NHP]). The association between EBOV neutralizing antibodies, glycoprotein (GP)-binding antibodies, and GP-reactive T cells and survival in NHP was assessed by logistic regression analysis. Binding antibodies against the EBOV surface GP were identified as the immune parameter with the strongest correlation to survival post EBOV challenge, and used to infer the predicted protective effect of the vaccine in humans using published data from phase I studies. The human vaccine-elicited EBOV GP-binding antibody levels are in a range associated with significant protection against mortality in NHP. Based on this immunobridging analysis, the EBOV GP-specific-binding antibody levels elicited by the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in humans will likely provide protection against EBOV disease.
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影响因子：
7.2
作者：
Golding, Hana;Khurana, Surender;Zaitseva, Marina
通讯作者：
Zaitseva, Marina
DOI：
10.1016/s0140-6736(16)32621-6
发表时间：
2017-02-04
期刊：
Lancet (London, England)
影响因子：
--
作者：
Henao-Restrepo AM;Camacho A;Longini IM;Watson CH;Edmunds WJ;Egger M;Carroll MW;Dean NE;Diatta I;Doumbia M;Draguez B;Duraffour S;Enwere G;Grais R;Gunther S;Gsell PS;Hossmann S;Watle SV;Kondé MK;Kéïta S;Kone S;Kuisma E;Levine MM;Mandal S;Mauget T;Norheim G;Riveros X;Soumah A;Trelle S;Vicari AS;Røttingen JA;Kieny MP
通讯作者：
Kieny MP
DOI：
10.1093/infdis/jiv304
发表时间：
2015-12-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Fitzpatrick G;Vogt F;Moi Gbabai OB;Decroo T;Keane M;De Clerck H;Grolla A;Brechard R;Stinson K;Van Herp M
通讯作者：
Van Herp M
影响因子：
5.5
作者：
Kennedy, RC;Shearer, MH;Hildebrand, W
通讯作者：
Hildebrand, W
影响因子：
6.4
作者：
Khan, AS;Tshioko, FK;Ksiazek, TG
通讯作者：
Ksiazek, TG