Levine S, Dillman T R, Montgomery P C
Department of Immunology and Microbiology, Wayne State University, School of Medicine, Detroit, Michigan 48201.
Proc Soc Exp Biol Med. 1989 Apr;190(4):349-56. doi: 10.3181/00379727-190-42871.
A lyophilized subunit vaccine prepared from purified respiratory syncytial virus, which contained the envelope glycoproteins F and G and the nonglycosylated matrix protein VPM, was tested in SJL mice for its ability to protect the lungs of mice from intranasal viral challenge. Initially, the mice were injected subcutaneously with one, two, or three doses of 5 or 25 micrograms of vaccine in 50% complete Freund's adjuvant or with complete Freund's adjuvant or phosphate-buffered saline only. Although none of the mice produced neutralizing serum antibody, three doses of 25 micrograms elicited antibodies to F, G, and VPM. Despite the absence of detectable neutralizing antibodies, the lungs of 93% of the vaccinated mice were protected from intranasal viral challenge. Because the initial protocol did not elicit neutralizing antibodies and a few single-dose animals were not protected, a second vaccine trial was carried out. For these studies the priming dose was increased to 50 micrograms, which was followed, in half the vaccine recipients, by a second dose of 25 micrograms. Mice given the priming dose of vaccine produced antibody to G and showed no neutralizing activity, whereas the mice given two doses of vaccine produced antibodies to G, F, and VPM and also displayed neutralizing activity for respiratory syncytial virus. The lungs of 100% of the vaccine recipients in this trial were protected from intranasal challenge. Although the vaccine elicited antibody to VPM, this response did not correlate with protection. In addition, examination of the sera from unimmunized mice recovering from respiratory syncytial virus infection revealed a serum antibody profile similar to that noted for humans, lacking antibody to VPM. Thus, the data show that a combined glycoprotein subunit vaccine affords complete protection to viral challenge and offers an approach to develop a multivalent subunit vaccine.
一种由纯化呼吸道合胞病毒制备的冻干亚单位疫苗，其包含包膜糖蛋白F和G以及非糖基化基质蛋白VPM，在SJL小鼠中进行了测试，以评估其保护小鼠肺部免受鼻内病毒攻击的能力。最初，小鼠皮下注射一剂、两剂或三剂5或25微克疫苗（溶于50%完全弗氏佐剂中），或仅注射完全弗氏佐剂或磷酸盐缓冲盐水。尽管没有一只小鼠产生中和血清抗体，但三剂25微克疫苗可引发针对F、G和VPM的抗体。尽管没有可检测到的中和抗体，但93%接种疫苗的小鼠肺部受到保护，免受鼻内病毒攻击。由于最初的方案未引发中和抗体，且少数单剂量动物未得到保护，因此进行了第二次疫苗试验。在这些研究中，启动剂量增加到50微克，一半的疫苗接种者随后接受第二剂25微克疫苗。接受启动剂量疫苗的小鼠产生了针对G的抗体，但没有中和活性，而接受两剂疫苗的小鼠产生了针对G、F和VPM的抗体，并且对呼吸道合胞病毒也表现出中和活性。在该试验中，100%的疫苗接种者肺部受到保护，免受鼻内攻击。尽管疫苗引发了针对VPM的抗体，但这种反应与保护作用无关。此外，对从呼吸道合胞病毒感染中恢复的未免疫小鼠血清的检测显示，其血清抗体谱与人类相似，缺乏针对VPM的抗体。因此，数据表明，一种联合糖蛋白亚单位疫苗能为病毒攻击提供完全保护，并为开发多价亚单位疫苗提供了一种方法。
