A protective multiple gene-deleted African swine fever virus genotype II, Georgia 2007/1, expressing a modified non-haemadsorbing CD2v protein.
A protective multiple gene-deleted African swine fever virus genotype II, Georgia 2007/1, expressing a modified non-haemadsorbing CD2v protein.
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DOI：
10.1080/22221751.2023.2265661
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发表时间：
2023-12
影响因子：
13.2
通讯作者：
Dixon, Linda K.
中科院分区：
文献类型：
--
作者：
Rathakrishnan, Anusyah;Reis, Ana L.;Petrovan, Vlad;Goatley, Lynnette C.;Moffat, Katy;Lui, Yuan;Vuong, Mai T.;Ikemizu, Shinji;Davis, Simon J.;Dixon, Linda K.
非洲猪瘟病毒是一种复杂的DNA病毒，在猪和野猪中造成高致死率，并具有巨大的社会经济影响。通过引入单或双氨基酸替代来减少或消除与红细胞的结合并降低病毒在血液中的持久性，构建了一种减毒基因II型毒株。突变型CD2v蛋白在感染细胞表面的表达水平与野生型蛋白相似。三种重组病毒也缺失了K145R、EP153R和一种病毒的DP148R基因。在猪免疫后，该病毒在CD2v Q96R中替换了一个氨基酸，诱导了中等水平的复制，并对强毒ASFV具有100%的保护作用。另外两种重组病毒在CD2v、Q96R和K108D中替换了两个氨基酸，并且在体外诱导不与红细胞结合。在免疫猪中，检测到血液中的病毒水平降低，并且检测到强烈的早期asfv特异性抗体和细胞反应。攻毒后，观察到攻毒病毒的低至中度复制。用删除DP148R基因的病毒免疫的猪，攻毒后的临床症状减少。在不同剂量范围内，保护水平保持在83-100%。对病毒GeorgiaΔDP148RΔK145RΔEP153R-CD2v_mutantQ96R/K108D的进一步实验表明，病毒在组织中的传播水平低，高剂量时出现短暂的临床症状。结果支持进一步评价GeorgiaΔDP148RΔK145RΔEP153R-CD2v_mutantQ96R/K108D作为候选疫苗。
African swine fever virus is a complex DNA virus that causes high fatality in pigs and wild boar and has a great socio-economic impact. An attenuated genotype II strain was constructed by replacing the gene for wildtype CD2v protein with versions in which single or double amino acid substitutions were introduced to reduce or abrogate the binding to red blood cells and reduce virus persistence in blood. The mutant CD2v proteins were expressed at similar levels to the wildtype protein on the surface of infected cells. Three recombinant viruses also had K145R, EP153R, and in one virus DP148R genes deleted. Following immunization of pigs, the virus with a single amino acid substitution in CD2v, Q96R, induced moderate levels of replication, and 100% protection against virulent ASFV. Two additional recombinant viruses had two amino acid substitutions in CD2v, Q96R, and K108D, and induced no binding to red blood cells in vitro. In immunized pigs, reduced levels of virus in blood and strong early ASFV-specific antibody and cellular responses were detected. After challenge low to moderate replication of challenge virus was observed. Reduced clinical signs post-challenge were observed in pigs immunized with the virus from which DP148R gene was deleted. Protection levels of 83–100% were maintained across a range of doses. Further experiments with virus GeorgiaΔDP148RΔK145RΔEP153R-CD2v_mutantQ96R/K108D showed low levels of virus dissemination in tissue and transient clinical signs at high doses. The results support further evaluation of GeorgiaΔDP148RΔK145RΔEP153R-CD2v_mutantQ96R/K108D as a vaccine candidate.
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影响因子：
5.4
作者：
Rathakrishnan A;Connell S;Petrovan V;Moffat K;Goatley LC;Jabbar T;Sánchez-Cordón PJ;Reis AL;Dixon LK
通讯作者：
Dixon LK
影响因子：
5.7
作者：
BODIAN, DL;JONES, EY;DAVIS, SJ
通讯作者：
DAVIS, SJ
DOI：
10.4049/jimmunol.2200813
发表时间：
2023-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Huang, Li;Chen, Weiye;Weng, Changjiang
通讯作者：
Weng, Changjiang
影响因子：
4.7
作者：
Rathakrishnan, Anusyah;Moffat, Katy;Dixon, Linda K.
通讯作者：
Dixon, Linda K.
影响因子：
5.4
作者：
Goatley, Lynnette C.;Dixon, Linda K.
通讯作者：
Dixon, Linda K.