Division of Avian Infectious Diseases, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, The Chinese Academy of Agricultural Sciences, Harbin, China.
PLoS One. 2013;8(1):e53340. doi: 10.1371/journal.pone.0053340. Epub 2013 Jan 3.
Herpesvirus of turkey (HVT) as a vector to express the haemagglutinin (HA) of avian influenza virus (AIV) H5 was developed and its protection against lethal Marek's disease virus (MDV) and highly pathogenic AIV (HPAIV) challenges was evaluated previously. It is well-known that avirulemt MDV type 1 vaccines are more effective than HVT in prevention of lethal MDV infection. To further increase protective efficacy against HPAIV and lethal MDV, a recombinant MDV type 1 strain 814 was developed to express HA gene of HPAIV H5N1.
METHODOLOGY/PRINCIPAL FINDINGS: A recombinant MDV-1 strain 814 expressing HA gene of HPAIV H5N1 virus A/goose/Guangdong/3/96 at the US2 site (rMDV-HA) was developed under the control of a human CMV immediate-early promoter. The HA expression in the rMDV-HA was tested by immunofluorescence and Western blot analyses, and in vitro and in vivo growth properties of rMDV-HA were also analyzed. Furthermore, we evaluated and compared the protective immunity of rMDV-HA and previously constructed rHVT-HA against HPAIV and lethal MDV. Vaccination of chickens with rMDV-HA induced 80% protection against HPAIV, which was better than the protection rate by rHVT-HA (66.7%). In the animal study with MDV challenge, chickens immunized with rMDV-HA were completely protected against virulent MDV strain J-1 whereas rHVT-HA only induced 80% protection with the same challenge dose.
CONCLUSIONS/SIGNIFICANCE: The rMDV-HA vaccine was more effective than rHVT-HA vaccine for protection against lethal MDV and HPAIV challenges. Therefore, avirulent MDV type 1 vaccine is a better vector than HVT for development of a recombinant live virus vaccine against virulent MDV and HPAIV in poultry.
火鸡疱疹病毒(HVT)作为载体表达禽流感病毒(AIV)H5 的血凝素(HA)已被开发出来,其对致死性马立克氏病病毒(MDV)和高致病性 AIV(HPAIV)的保护作用已得到评估。众所周知,无致弱力的 MDV 1 型疫苗在预防致死性 MDV 感染方面比 HVT 更有效。为了进一步提高对 HPAIV 和致死性 MDV 的保护效力,开发了表达 HPAIV H5N1 HA 基因的重组 MDV 1 型 814 株。
方法/主要发现:在人 CMV 早期启动子的控制下,在 US2 位点表达 HPAIV H5N1 病毒 A/鹅/广东/3/96 HA 基因的重组 MDV-1 株 814(rMDV-HA)被开发出来。通过免疫荧光和 Western blot 分析检测 rMDV-HA 的 HA 表达,并分析 rMDV-HA 的体外和体内生长特性。此外,我们评估并比较了 rMDV-HA 和之前构建的 rHVT-HA 对 HPAIV 和致死性 MDV 的保护免疫。rMDV-HA 疫苗接种可使鸡对 HPAIV 的保护率达到 80%,优于 rHVT-HA(66.7%)的保护率。在 MDV 攻毒的动物研究中,用 rMDV-HA 免疫的鸡完全免受强毒 MDV 株 J-1 的侵害,而用相同剂量的 rHVT-HA 仅诱导 80%的保护率。
结论/意义:rMDV-HA 疫苗比 rHVT-HA 疫苗更有效地预防致死性 MDV 和 HPAIV 挑战。因此,无致弱力的 MDV 1 型疫苗是比 HVT 更好的载体,可用于开发针对家禽强毒 MDV 和 HPAIV 的重组活病毒疫苗。