Singh Pratik, Schnitzlein William M, Tripathy Deoki N
Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
Avian Dis. 2005 Sep;49(3):401-8. doi: 10.1637/7340-020705R.1.
Fowlpox virus (FWPV) has been isolated from vaccinated chicken flocks during subsequent fowlpox outbreaks that were characterized by a high degree of mortality and significant economic losses. This inability of current vaccines to induce adequate immunity in poultry could be reflective of an antigenic and/or biologic distinctiveness of FWPV field isolates. In this regard, whereas an infectious reticuloendotheliosis virus (REV) provirus is present in the majority of the field viruses' genomes, only remnants of REV long terminal repeats (LTR) have been retained in the DNAs of each vaccine strain. Although it has not been demonstrated whether the partial LTRs can provide an avenue for FWPV to reacquire the REV provirus by homologous recombination, utilizing viruses of which genomes lack any known integrated retroviral sequences could resolve concern over this issue. Therefore, such an entity was created by genetically modifying a recently isolated field strain of FWPV. This selection, in lieu of a commercial vaccine virus, as the progenitor was based on the probability that a virus circulating in the environment would be more antigenically similar to others in this locale and thus might be a better candidate for vaccine development. A comparison in vivo of the pathogenic traits of the parental wild-type field isolate, its genetically modified progeny, and a rescue mutant in whose genome the REV provirus was inserted at its previous location, indicated that elimination of the provirus sequence correlated with reduced virulence. However, even with elimination of the parasitic REV, the modified FWPV was still slightly more invasive than a commercial vaccine virus. Interestingly, both types of attenuated FWPV elicited a similar degree of antibody production in inoculated chickens and afforded them protection against a subsequent challenge by a field virus, the origin of which was temporally and geographically distinct from that of the progenitor strain. Due to its antigenicity being retained despite a decrease in virulence, this REV-less FWPV could potentially be developed as a vaccine against fowlpox.
在随后发生的以高死亡率和重大经济损失为特征的禽痘疫情中,已从接种过疫苗的鸡群中分离出禽痘病毒(FWPV)。当前疫苗无法在家禽中诱导足够免疫力,这可能反映出FWPV野外分离株的抗原性和/或生物学独特性。在这方面,虽然大多数野外病毒基因组中存在传染性网状内皮组织增生症病毒(REV)前病毒,但每个疫苗株的DNA中仅保留了REV长末端重复序列(LTR)的残余部分。尽管尚未证明部分LTR是否能为FWPV通过同源重组重新获得REV前病毒提供途径,但利用基因组中缺乏任何已知整合逆转录病毒序列的病毒可以解决对此问题的担忧。因此,通过对最近分离的FWPV野外株进行基因改造创建了这样一个实体。选择该野外株而非商业疫苗病毒作为始祖,是基于这样的可能性,即在环境中传播的病毒在抗原性上可能与该地区的其他病毒更相似,因此可能是疫苗开发的更好候选者。对亲本野生型野外分离株、其基因改造后代以及在其基因组中REV前病毒插入其先前位置的拯救突变体的致病特性进行体内比较,结果表明前病毒序列的消除与毒力降低相关。然而,即使消除了寄生性REV,改造后的FWPV仍比商业疫苗病毒略具侵袭性。有趣的是,两种减毒FWPV在接种鸡中引发的抗体产生程度相似,并为它们提供了针对野外病毒后续攻击的保护,该野外病毒的来源在时间和地理上与始祖株不同。由于其在毒力降低的情况下仍保留抗原性,这种无REV的FWPV有可能被开发成一种抗禽痘疫苗。