Tartaglia J, Pincus S, Paoletti E
Bucknell University, Lewisburg, Pennsylvania.
Crit Rev Immunol. 1990;10(1):13-30.
The advent of recombinant DNA techniques and advances in immunology have provided a means for dissecting the immunobiology of disease-causing agents. Identification and expression of individual genes from the pathogens in heterologous systems, such as VV, have yielded valuable information regarding structural properties of the gene products and their role in eliciting protective immunity. Targets of both humoral and/or cellular immunity for many disease-causing agents have been identified or confirmed using a VV expression system (Section IV). Additionally, specific VV recombinants have induced a protective immune response in experimental animals. The ability of VV recombinants to induce pertinent immune responses necessary for protection, the potential to develop polyvalent vaccines, and the successful history of VV as an immunizing agent provide the impetus for engineering VV as a live recombinant vaccine candidate. Critical to the refinement of poxviruses as recombinant immunizing agents is a more in-depth knowledge of the molecular biology of these viruses. Although significant advances have been made in this area within the past 10 years, a greater understanding of the mechanisms governing gene expression and viral virulence factors should enable the development of more safe and effective vaccine candidates. Progression of VV vector technology to other members of the poxvirus family has been successful. Development of other poxviruses as vectors may, therefore, provide a means of generating host-restricted vaccines. Fowlpox recombinant viruses, for instance, may yield candidate vaccines in the poultry industry. Interestingly, it was also demonstrated that these host-restricted recombinant viruses can be used as immunizing vehicles in other species. The ability of a nonreplicating viral vector to elicit a protective immune response is especially intriguing in light of the observation by Morgan et al. that a VV/EBV gp340/220 recombinant, derived from an avirulent VV strain, was unable to protect cottontop tamarins from a live EBV challenge.
重组DNA技术的出现和免疫学的进展为剖析致病因子的免疫生物学提供了一种手段。在诸如痘苗病毒（VV）等异源系统中对病原体的单个基因进行鉴定和表达，已经产生了关于基因产物的结构特性及其在引发保护性免疫中作用的有价值信息。使用VV表达系统已经鉴定或确认了许多致病因子的体液免疫和/或细胞免疫靶点（第四节）。此外，特定的VV重组体已在实验动物中诱导出保护性免疫反应。VV重组体诱导保护所需相关免疫反应的能力、开发多价疫苗的潜力以及VV作为免疫剂的成功历史，为将VV工程改造为活重组疫苗候选物提供了动力。将痘病毒优化为重组免疫剂的关键在于对这些病毒分子生物学有更深入的了解。尽管在过去10年里该领域已取得重大进展，但对基因表达调控机制和病毒毒力因子有更深入的了解应能推动开发出更安全有效的疫苗候选物。将VV载体技术推广到痘病毒家族的其他成员已获成功。因此，开发其他痘病毒作为载体可能提供一种生产宿主限制性疫苗的方法。例如，禽痘重组病毒可能为家禽业提供候选疫苗。有趣的是，还证明这些宿主限制性重组病毒可在其他物种中用作免疫载体。鉴于摩根等人观察到源自无毒VV株的VV/EBV gp340/220重组体无法保护棉顶狨免受活EBV攻击，非复制性病毒载体引发保护性免疫反应的能力尤其引人关注。
