Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401, USA.
Vaccine. 2011 Oct 13;29(44):7659-69. doi: 10.1016/j.vaccine.2011.07.140. Epub 2011 Aug 12.
Vaccinia virus deleted for the innate immune evasion gene, E3L, has been shown to be highly attenuated and yet induces a protective immune response against challenge by homologous virus in a mouse model. In this manuscript the NYCBH vaccinia virus vaccine strain was compared to NYCBH vaccinia virus deleted for E3L (NYCBHΔE3L) in a rabbitpox virus (RPV) challenge model. Upon scarification, both vaccines produced a desired skin lesion, although the lesion produced by NYCBHΔE3L was smaller. Both vaccines fully protected rabbits against lethal challenge by escalating doses of RPV, from 10LD(50) to 1000LD(50). A single dose of NYCBHΔE3L protected rabbits from weight loss, fever, and clinical symptoms following the lowest dose challenge of 10LD(50), however it allowed a moderate level of RPV replication at the challenge site, some spread to external skin and mucosal surfaces, and increased numbers of secondary lesions as compared to vaccination with NYCBH. Alternately, two doses of NYCBHΔE3L fully protected rabbits from weight loss, fever, and clinical symptoms, following challenge with 100-1000LD(50) RPV, and it prevented development of secondary lesions similar to protection seen with NYCBH. Finally, vaccination with either one or two doses of NYCBHΔE3L resulted in similar neutralizing antibody titers following RPV challenge as compared to titers obtained by vaccination with NYCBH. These results support the efficacy of the attenuated NYCBHΔE3L in protection against an orthologous poxvirus challenge.
痘苗病毒中先天免疫逃逸基因 E3L 的缺失株已被证实具有高度减毒特性，并且在小鼠模型中能够诱导针对同源病毒的保护性免疫反应。在本研究中，我们比较了 NYCBH 痘苗病毒疫苗株和 NYCBH 缺失 E3L 株（NYCBHΔE3L）在兔痘病毒（RPV）挑战模型中的效果。划痕接种后，两种疫苗均产生了理想的皮肤损伤，尽管 NYCBHΔE3L 引起的损伤较小。两种疫苗均能完全保护兔子免受致死剂量 RPV 的致死性攻击，从 10LD（50）到 1000LD（50）。单次接种 NYCBHΔE3L 可保护兔子免受 10LD（50）最低剂量攻击后体重减轻、发热和临床症状的影响，但在挑战部位允许中等水平的 RPV 复制，一些病毒扩散到外部皮肤和黏膜表面，并导致更多的继发损伤，与 NYCBH 疫苗接种相比。相反，两次接种 NYCBHΔE3L 可完全保护兔子免受 100-1000LD（50）RPV 攻击后体重减轻、发热和临床症状的影响，并可预防与 NYCBH 相似的继发损伤的发展。最后，与 NYCBH 疫苗接种相比，单次或两次接种 NYCBHΔE3L 后，在 RPV 攻击后产生的中和抗体滴度相似。这些结果支持 NYCBHΔE3L 在预防同源痘病毒攻击方面的有效性。
