CORONAVIRUS IMMUNOGENS
CORONAVIRUS IMMUNOGENS
复制标题
DOI：
10.1016/0378-1135(93)90030-b
复制
发表时间：
1993-11-01
影响因子：
3.3
通讯作者：
SAIF, LJ
中科院分区：
文献类型：
--
作者：
SAIF, LJ
冠状病毒（CV）感染多种家畜、家禽和伴侣动物。它们属于至少五个抗原组。 CV 会引起呼吸道和/或肠道的局部感染，但猫传染性腹膜炎病毒 (FIPV) 和血凝性脑脊髓炎 (HEV) 会引起全身感染。肠致病性CV感染绒毛肠细胞，导致绒毛萎缩，导致吸收不良性腹泻。几种CV（牛CV-BCV、猪呼吸道CV-PRCV、传染性支气管炎病毒-IBV）会引起呼吸道疾病。目前的证据表明，针对肠道和呼吸道CV感染的保护作用是由CV复制的主要位点的被动或主动免疫介导的。诱导被动免疫的母亲疫苗接种方法包括使用灭活和改良的活病毒疫苗。改良活病毒和 Ts 突变体 CV (FIPV) 也用作口服或鼻内疫苗，以诱导主动粘膜免疫。这些疫苗在该领域的成功常常受到许多潜在问题的影响。冠状病毒是球形、有包膜的病毒，直径范围为 80-160 nm，含有正链 RNA 基因组。它们具有明显的表面尖刺，一些物种显示出较小的表面突起边缘，据信是血凝素（HE）。冠状病毒具有 3 至 4 种结构蛋白：刺突 (S) 糖蛋白 (150-200 kDa)、整合膜糖蛋白 (M；20-30 kDa) 和核衣壳磷蛋白 (N；43-50 kDa)。 CV 的一个子集（BCV、HEV、火鸡 CV）在病毒体表面具有第三种糖蛋白，即 HE (60-65 kDa)。这些蛋白质可以使用混合单克隆抗体 (mAb) 在 ELISA 中针对每种蛋白质的不同表位进行定量。大多数研究都集中在 S 蛋白作为 CV 疫苗的候选抗原，因为它会诱导病毒中和 (VN) 抗体。然而，HE 蛋白刺激 VN 和 HE 抑制抗体的产生，M 蛋白诱导抗体在补体存在的情况下中和病毒。将体外 VN 抗体活性与体内保护联系起来的尝试表明，在一些研究中，VN mAb 被动转移至 S 或 HE 蛋白可提供针对 CV 攻击的被动保护，但在其他研究中则不然。其他研究表明其他 CV 蛋白在免疫中可能发挥作用。针对传染性胃肠炎 (TGEV) M 蛋白的单克隆抗体研究为 M 蛋白在猪血白细胞诱导 αIFN 中的直接作用提供了证据。这种现象对 TGEV 免疫的潜在意义尚不清楚。类似地，IBV的研究表明，T细胞识别的决定簇驻留在N蛋白上，并且这些决定簇可能在IBV的异源菌株之间共享，从而导致交叉保护的诱导。因此，N 蛋白上的表位对于诱导细胞介导的免疫 (CMI) 可能很重要。 CMI 可能在保护猫免受 FIPV 侵害方面发挥重要作用，因为通过诱导免疫复合物和抗体依赖性增强 FIPV 对巨噬细胞的感染性，诱导 FIPV S 蛋白的循环抗体有助于疾病发病机制。需要加深对动物自然 CV 感染后抗体和 CMI 反应的了解，以确定诱导保护性的抗原和表位 免疫反应。 CV结构蛋白基因在各种载体中的表达将为未来宿主物种的免疫原性研究提供所需的重组蛋白。此外，在肠道中复制并表达冠状病毒基因的活rDNA载体可能会提供新一代冠状病毒疫苗。
Coronaviruses (CV) infect a variety of livestock, poultry and companion animals. They belong to at least five antigenic groups. CV cause localized infections of the respiratory and/or intestinal tracts, with the exception of feline infectious peritonitis virus (FIPV) and hemagglutinating encephalomyelitis (HEV) which cause systemic infections. The enteropathogenic CV infect the villous enterocytes resulting in villous atrophy leading to malabsorptive diarrhea. Several CV (bovine CV-BCV, porcine respiratory CV-PRCV, infectious bronchitis virus-IBV) cause respiratory disease.Current evidence indicates that protection against enteric and respiratory CV infections is mediated by passive or active immunity at the primary site of CV replication. Maternal vaccination approaches to induce passive immunity include the use of inactivated and modified live viral vaccines. Modified live viruses and a Ts mutant CV (FIPV) are also used as oral or intranasal vaccines to induce active mucosal immunity. The success of these vaccines in the field is often compromised by a number of potential problems.Coronaviruses are spherical, enveloped viruses, ranging from 80-160 nm in diameter and containing a positive-stranded RNA genome. They possess prominent surface spikes and some species display a fringe of smaller surface projections believed to be the hemagglutinin (HE). Coronaviruses possess 3 to 4 structural proteins: the spike (S) glycoprotein (150-200 kDa), the integral membrane glycoprotein (M; 20-30 kDa) and the nucleocapsid phosphoprotein (N; 43-50 kDa). A subset of CV (BCV, HEV, turkey CV) possess a third glycoprotein on the virion surface, the HE (60-65 kDa). These proteins can be quantitated using pooled monoclonal antibodies (mAb) to distinct epitopes of each protein in ELISA.Most research has focused on the S protein as a candidate antigen for CV vaccines since it induces virus neutralizing (VN) antibodies. However the HE protein stimulates the production of VN and HE inhibiting antibodies and the M protein induces antibodies that neutralize virus in the presence of complement. Attempts to correlate in vitro VN antibody activity with in vivo protection have shown that the passive transfer of VN mAb to the S or HE protein conferred passive protection against CV challenge in some studies, but not others. Additional research has implicated a possible role for other CV proteins in immunity. Studies of mAb to the M protein of transmissible gastroenteritis (TGEV) have provided evidence for a direct role of the M protein in the induction of alphaIFN by porcine blood leukocytes. The potential significance of this phenomenon to immunity to TGEV is unclear. Similarly, studies of IBV have suggested that determinants recognized by T cells reside on the N protein and these determinants may be shared among heterologous strains of IBV, resulting in the induction of cross-protection. Thus epitopes on the N protein may be important for induction of cell mediated immunity (CMI). CMI may play an important role in protection of cats against FIPV, since induction of circulating antibodies to the S protein of FIPV contributes to disease pathogenesis by the induction of immune complexes and antibody dependent enhancement of the infectivity of FIPV for macrophages.An increased understanding of antibody and CMI responses following natural CV infections in animals is needed to identify the antigens and epitopes that induce protective immune responses. The expression of CV structural protein genes in various vectors will provide the recombinant proteins needed for future immunogenicity studies in the host species. Furthermore, live rDNA vectors that replicate in the gut and express coronavirus genes may provide a new generation of coronavirus vaccines.