Richardson J, Moraillon A, Crespeau F, Baud S, Sonigo P, Pancino G
Génétique des Virus (ICGM-CNRS UPR 0415), Institut Cochin de Génétique Moléculaire, Paris, France.
J Virol. 1998 Mar;72(3):2406-15. doi: 10.1128/JVI.72.3.2406-2415.1998.
Recent advances in the quantitative assessment of viral burden, by permitting the extension of criteria applied to assess the efficacy of vaccines from all-or-none protection to diminution of the viral burden, may allow the identification of original immunogens of value in combined vaccines. Peptides corresponding to three domains of the envelope glycoproteins of feline immunodeficiency virus that are recognized during natural infection were used to immunize cats. After challenge with a primary isolate of feline immunodeficiency virus, the development of acute infection was monitored by quantitative assessment of the viral burden in plasma and tissues by competitive reverse transcription-PCR, by measurement of the humoral response developed to viral components, and by lymphocyte subset analysis. Whereas immunization with two peptides derived from the surface glycoprotein had no effect on the early course of infection, immunization with a peptide derived from the transmembrane glycoprotein delayed infection, as reflected by a diminished viral burden in the early phase of primary infection and delayed seroconversion. This peptide, located in the membrane-proximal region of the extracellular domain, has homology to an epitope of human immunodeficiency virus type 1 recognized by a broadly neutralizing monoclonal antibody. These results suggest that lentivirus transmembrane glycoproteins share a determinant in the juxtamembrane ectodomain which could be of importance in the design of vaccines against AIDS.
病毒载量定量评估方面的最新进展,通过允许将用于评估疫苗效力的标准从全或无保护扩展到病毒载量的减少,可能有助于识别联合疫苗中有价值的原始免疫原。使用与猫免疫缺陷病毒包膜糖蛋白三个结构域相对应的肽来免疫猫,这些结构域在自然感染期间会被识别。在用猫免疫缺陷病毒的原始分离株进行攻击后,通过竞争性逆转录聚合酶链反应对血浆和组织中的病毒载量进行定量评估、测量针对病毒成分产生的体液反应以及进行淋巴细胞亚群分析,来监测急性感染的发展。虽然用源自表面糖蛋白的两种肽进行免疫对感染的早期进程没有影响,但用源自跨膜糖蛋白的一种肽进行免疫延迟了感染,这在原发性感染的早期阶段病毒载量减少和血清转化延迟中得到体现。这种肽位于细胞外结构域的膜近端区域,与被一种广泛中和单克隆抗体识别的1型人类免疫缺陷病毒的一个表位具有同源性。这些结果表明,慢病毒跨膜糖蛋白在近膜胞外结构域共享一个决定簇,这在抗艾滋病疫苗的设计中可能很重要。