USDA, Agricultural Research Service, United States National Poultry Research Center, Avian Disease & Oncology Laboratory, East Lansing, MI 48823,
USDA, Agricultural Research Service, United States National Poultry Research Center, Avian Disease & Oncology Laboratory, East Lansing, MI 48823.
Avian Dis. 2021 Jun;65(2):241-249. doi: 10.1637/aviandiseases-D-20-00122.
Marek's disease virus (MDV) is an important poultry pathogen that is controlled through widespread vaccination with avirulent and attenuated strains. However, continued evolution of field viruses to higher virulence has required ongoing improvement of available vaccine strains, and these vaccine strains offer an attractive platform for designing recombinant vector vaccines with cross-protection against MDV and additional pathogens. Recent reports of failures in vaccine licensing trials of positive controls to reach appropriately high levels of Marek's disease incidence prompted us to evaluate possible combinations of outbred specific-pathogen-free layer lines and alternative virulent challenge strains that could provide more consistent models for serotype 3 vectored vaccine development. Choice of layer line and virulent MDV challenge strain each contributed to the ability of a challenge model to reach 80% virulence in unvaccinated positive control groups in the majority of trials, without overwhelming serotype 3 vectored vaccine protection in vaccinated groups. Conversely, reducing challenge virus dose by a factor of four, or vaccine dose by half, had no consistent effect across these models. Although MDV strain 617A had the most potential as an alternative to strains that are currently approved for licensing trials, no combination of layer line and challenge virus consistently met the goals for a successful challenge model in all study replicates, indicating that high variability is an inherent difficulty in MDV challenge studies, at least when outbred birds are used.
马立克氏病病毒（MDV）是一种重要的家禽病原体，通过广泛接种无毒性和减毒菌株来进行控制。然而，野毒株不断进化为更高的毒力，这要求对现有疫苗株进行持续改进，这些疫苗株为设计针对 MDV 和其他病原体的具有交叉保护作用的重组载体疫苗提供了有吸引力的平台。最近，阳性对照疫苗许可试验失败的报告表明，需要改进现有的疫苗株，以达到适当高的马立克氏病发病率水平，这促使我们评估了不同的方法，包括选用不同的、具有特定病原的无特定病原体鸡系和替代的强毒力攻毒株，以提供更一致的 3 型血清型载体疫苗开发模型。选择鸡系和强毒力 MDV 攻毒株，在大多数试验中，对未接种疫苗的阳性对照组达到 80%的毒力具有重要作用，而对接种疫苗的对照组中 3 型血清型载体疫苗的保护作用没有影响。相反，将攻毒病毒剂量减少 4 倍或疫苗剂量减少一半，对这些模型没有一致的影响。虽然 MDV 株 617A 作为替代目前批准用于许可试验的菌株具有最大的潜力，但在所有研究重复中，没有一种鸡系和攻毒病毒的组合能够始终满足成功攻毒模型的目标，这表明在 MDV 攻毒研究中，高变异性是一个固有的困难，至少在使用杂交鸡时是这样。
