VACCINE FOR EQUINE INFECTIOUS ANEMIA VIRUS VARIANTS

逆转录病毒引起人类和动物的疾病， 免疫抑制 慢病毒（非致癌亚家族）是 包括HTLV-III/LAV/ARV人类病毒组;小反刍动物 山羊进行性关节炎-脑炎病毒群 肺炎病毒;和马传染性贫血病毒（EIAV）。 控制 慢病毒是困难的，因为前病毒的持久性和变化， env基因序列导致表面抗原性变异 糖蛋白 本提案的长期目标是了解 表面关键功能区域的结构组织 EIAV是一种独特的逆转录病毒，可用于抗原性研究 变化和持久性。 这项调查将研究如何一个单一的 功能区-受体结合位点-可用于引发 与EIAV抗原变异体反应的中和抗体应答。 这些抗体单独和联合使用的保护作用 具有针对不变EIAV的细胞毒性T淋巴细胞应答 然后评估感染细胞上的抗原。 述方法将 包括从纯化病毒体表面分离受体结合位点 通过蛋白水解消化和HPLC分析糖蛋白，构建结合 通过肽合成或通过表达克隆env 载体系统中的基因，用受体结合位点免疫马 类似物和刺激细胞毒性T细胞的不变EIAV抗原 淋巴细胞和用EIAV抗原变体攻击免疫的马。 具体目标是： 1.为了确定EIAV的抗原变体是否具有共同的受体， 结合位点 2.为了分离和表征病毒gp 90的片段， 受体结合位点 3.制备免疫化学上类似于 受体结合位点。 4.为了测试受体结合位点类似物引发免疫应答的能力， 马对EIAV抗原变体的交叉保护性免疫应答。 5.为了证明用不变性EIAV抗原免疫， 刺激细胞毒性T淋巴细胞将增强免疫， 受体结合位点类似物。

Retroviruses cause diseases in humans and animals, ranging from neoplasia to immunosuppression. Lentiviruses (a non-oncogenic subfamily) are comprised of the HTLV-III/LAV/ARV human virus group; the small ruminant virus group of caprine arthritis-encephalitis, visna and progressive pneumonia viruses; and equine infectious anemia virus (EIAV). Control of lentiviruses is difficult because of provirus persistence and changes in the env gene sequence resulting in antigenic variation of surface glycoproteins. The long term objective of this proposal is to understand the structural organization of critical functional regions of surface glycoproteins of EIAV, a unique retrovirus for studies of antigenic variation and persistence. This investigation will examine how a single functional region--the receptor binding site--can be used to elicit a neutralizing antibody response that reacts with EIAV antigenic variants. The protective effects of these antibodies both alone and in conjunction with a cytotoxic T lymphocyte response directed against invariant EIAV antigens on infected cells will then be evaluated. The methods will include isolating a receptor binding site from purified virion surface glycoproteins by proteolytic digestion and HPLC, constructing a binding site receptor analog by peptide synthesis or by expression of cloned env gene in a vector system, immunizing horses with the receptor binding site analog and with invariant EIAV antigens that stimulate cytotoxic T lymphocytes and challenging immunized horses with EIAV antigenic variants. The specific aims are: 1. To determine whether antigenic variants of EIAV have a common receptor binding site. 2. To isolate and characterize a fragment of viral gp90 containing the receptor binding site. 3. To make a synthetic or recombinant product immunochemically analogous to the receptor binding site. 4. To test the capacity of the receptor binding site analog to elicit a cross protective immune response in horses against EIAV antigenic variants. 5. To demonstrate that immunization with an invariant EIAV antigen that stimulates cytotoxic T lymphocytes will augment immunication with a receptor binding site analog.