Fooks A R, Jeevarajah D, Lee J, Warnes A, Niewiesk S, ter Meulen V, Stephenson J R, Clegg J C
Centre for Applied Microbiology and Research, Porton Down, Salisbury, UK.
J Gen Virol. 1998 May;79 ( Pt 5):1027-31. doi: 10.1099/0022-1317-79-5-1027.
The genes encoding the measles virus (MV) haemagglutinin (H) and fusion (F) proteins were placed under the control of the human cytomegalovirus immediate early promoter in a replication-deficient adenovirus vector. Immunofluorescence and radioimmune precipitation demonstrated the synthesis of each protein and biological activity was confirmed by the detection of haemadsorption and fusion activities in infected cells. Oral as well as parenteral administration of the H-expressing recombinant adenovirus elicited a significant protective response in mice challenged with MV. While the F-expressing adenovirus failed to protect mice, cotton rats immunized with either the H- or F-expressing recombinant showed reduced MV replication in the lungs. Antibodies elicited in mice following immunization with either recombinant had no in vitro neutralizing activity, suggesting a protective mechanism involving a cell-mediated immune response. This study demonstrates the feasibility of using oral administration of adenovirus recombinants to induce protective responses to heterologous proteins.
将编码麻疹病毒（MV）血凝素（H）和融合（F）蛋白的基因置于复制缺陷型腺病毒载体中人类巨细胞病毒立即早期启动子的控制之下。免疫荧光和放射免疫沉淀法证实了每种蛋白的合成，并且通过检测感染细胞中的血细胞吸附和融合活性确认了生物学活性。口服以及肠胃外给予表达H的重组腺病毒在受到MV攻击的小鼠中引发了显著的保护性反应。虽然表达F的腺病毒未能保护小鼠，但用表达H或F的重组体免疫的棉鼠肺部的MV复制减少。用任一重组体免疫后在小鼠中引发的抗体没有体外中和活性，提示存在涉及细胞介导免疫反应的保护机制。本研究证明了口服给予腺病毒重组体以诱导对异源蛋白产生保护性反应的可行性。
