Foreign Animal Disease Research Unit, Plum Island Animal Disease Center, U.S. Department of Agriculture, Agricultural Research Service, Orient, NY 11957, USA.
Foreign Animal Disease Research Unit, U.S. Department of Agriculture, Agricultural Research Service, National Bio and Agro-Defense Facility, Manhattan, KS 66502, USA.
Viruses. 2024 Feb 28;16(3):376. doi: 10.3390/v16030376.
The African swine fever virus (ASFV) mutant ASFV-G-∆I177L is a safe and efficacious vaccine which induces protection against the challenge of its parental virus, the Georgia 2010 isolate. Although a genetic DIVA (differentiation between infected and vaccinated animals) assay has been developed for this vaccine, still there is not a serological DIVA test for differentiating between animals vaccinated with ASFV-G-∆I177L and those infected with wild-type viruses. In this report, we describe the development of the ASFV-G-∆I177L mutant having deleted the gene, which encodes for the viral protein responsible for mediating the hemadsorption of swine erythrocytes. The resulting virus, ASFV-G-∆I177L/∆EP402R, does not have a decreased ability to replicates in swine macrophages when compared with the parental ASFV-G-∆I177L. Domestic pigs intramuscularly (IM) inoculated with either 10 or 10 HAD of ASFV-G-∆I177L/∆EP402R remained clinically normal, when compared with a group of mock-vaccinated animals, indicating the absence of residual virulence. Interestingly, an infectious virus could not be detected in the blood samples of the ASFV-G-∆I177L/∆EP402R-inoculated animals in either group at any of the time points tested. Furthermore, while all of the mock-inoculated animals presented a quick and lethal clinical form of ASF after the intramuscular inoculation challenge with 10 HAD of highly virulent parental field isolate Georgia 2010 (ASFV-G), all of the ASFV-G-∆I177L/∆EP402R-inoculated animals were protected, remaining clinically normal until the end of the observational period. Most of the ASFV-G-∆I177L/∆EP402R-inoculated pigs developed strong virus-specific antibody responses against viral antigens, reaching maximum levels at 28 days post inoculation. Importantly, all of the sera collected at that time point in the ASFV-G-∆I177L/∆EP402R-inoculated pigs did not react in a direct ELISA coated with the recombinant EP402R protein. Conversely, the EP402R protein was readily recognized by the pool of sera from the animals immunized with recombinant live attenuated vaccine candidates ASFV-G-∆I177L, ASFV-G-∆MGF, or ASFV-G-∆9GL/∆UK. Therefore, ASFV-G-∆I177L/∆EP402R is a novel, safe and efficacious candidate with potential to be used as an antigenically DIVA vaccine.
非洲猪瘟病毒（ASFV）突变株 ASFV-G-∆I177L 是一种安全有效的疫苗，可诱导对其亲本病毒（格鲁吉亚 2010 分离株）的保护。尽管已经为这种疫苗开发了一种基因差异免疫（DIVA）检测方法，但仍然没有一种血清学 DIVA 检测方法可以区分用 ASFV-G-∆I177L 接种的动物和感染野生型病毒的动物。在本报告中，我们描述了缺失编码介导猪红细胞吸附的病毒蛋白的 基因的 ASFV-G-∆I177L 突变株的开发。与亲本 ASFV-G-∆I177L 相比，产生的病毒 ASFV-G-∆I177L/∆EP402R 复制能力在猪巨噬细胞中没有降低。与一组模拟接种的动物相比，肌肉内（IM）接种 10 或 10 HAD 的 ASFV-G-∆I177L/∆EP402R 的家猪保持临床正常，表明没有残留毒力。有趣的是，在任何测试时间点，两组中都未在 ASFV-G-∆I177L/∆EP402R 接种动物的血液样本中检测到感染性病毒。此外，虽然所有模拟接种的动物在肌肉内接种高致病性亲本田间分离株格鲁吉亚 2010（ASFV-G）10 HAD 后迅速出现致命的 ASF 临床形式，但所有 ASFV-G-∆I177L/∆EP402R 接种的动物都受到保护，在观察期结束前保持临床正常。大多数接种 ASFV-G-∆I177L/∆EP402R 的猪对病毒抗原产生了强烈的病毒特异性抗体反应，在接种后 28 天达到最大水平。重要的是，在接种后的那个时间点，从接种了重组活减毒疫苗候选物 ASFV-G-∆I177L、ASFV-G-∆MGF 或 ASFV-G-∆9GL/∆UK 的动物收集的所有血清均未在包被重组 EP402R 蛋白的直接 ELISA 中反应。相反，EP402R 蛋白很容易被免疫了重组活减毒疫苗候选物 ASFV-G-∆I177L、ASFV-G-∆MGF 或 ASFV-G-∆9GL/∆UK 的动物的血清池识别。因此，ASFV-G-∆I177L/∆EP402R 是一种新型、安全、有效的候选疫苗，具有作为抗原差异免疫疫苗的潜力。
