Pearce E J, James S L, Hieny S, Lanar D E, Sher A
Immunology and Cell Biology, National Institutes of Allergy and Infectious Diseases, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1988 Aug;85(15):5678-82. doi: 10.1073/pnas.85.15.5678.
Paramyosin (Sm97), a 97-kDa myofibrillar protein identified by the unusually monospecific antibody response induced by intradermal vaccination of mice with a complex soluble worm antigen preparation (SWAP) of adult Schistosoma mansoni administered with bacillus Calmette-Guérin (BCG), was purified and tested for its capacity to protect mice against challenge infection. When administered intradermally with BCG at total doses of only 4-40 micrograms per mouse, both the native molecule and a recombinant expression product containing approximately 50% of the whole protein were found to confer significant resistance (26-33%) against challenge infection, while 2 mg of unfractionated SWAP was required to induce similar levels of protection. In addition, paramyosin was shown to stimulate T lymphocytes from vaccinated mice to produce lymphokines [e.g., gamma interferon (IFN-gamma)] that activate macrophages to kill schistosomula. Neither schistosome myosin nor a heterologous paramyosin from a different invertebrate genus were protective, indicating a requirement for specific epitopes in the immunization. That the protection induced by paramyosin involves a T-cell-mediated mechanism was supported by the failure of anti-paramyosin antibodies to passively transfer significant resistance to infection to recipient mice. Lymphocytes from mice vaccinated with paramyosin were found to produce IFN-gamma in response to living schistosomula, suggesting that during challenge infection of vaccinated hosts, paramyosin (a nonsurface antigen) may elicit a protective T-cell response as a consequence of its release from migrating parasite larvae. Paramyosin-depleted SWAP was also found to be protective as well as stimulatory for T lymphocytes from SWAP-vaccinated mice, indicating that other antigens in this preparation may have immunoprophylactic potential. In summary, these results (i) suggest that the induction of T-cell-dependent cell-mediated immunity against soluble nonsurface antigens may be an effective strategy for immunization against multicellular parasites and (ii) in the case of schistosomes, identify paramyosin as a candidate vaccine immunogen in this category.
副肌球蛋白（Sm97）是一种97 kDa的肌原纤维蛋白，通过用卡介苗（BCG）辅助皮内接种成年曼氏血吸虫的复合可溶性虫抗原制剂（SWAP）诱导小鼠产生异常单特异性抗体反应而得以鉴定。该蛋白经纯化后，对其保护小鼠抵抗攻击感染的能力进行了测试。当与BCG一起以每只小鼠仅4 - 40微克的总剂量皮内给药时，发现天然分子和含有约50%全蛋白的重组表达产物均能赋予对攻击感染的显著抗性（26 - 33%），而诱导类似保护水平则需要2毫克未分级的SWAP。此外，副肌球蛋白被证明能刺激接种疫苗小鼠的T淋巴细胞产生淋巴因子[如γ干扰素（IFN - γ）]，从而激活巨噬细胞杀死血吸虫幼虫。血吸虫肌球蛋白和来自不同无脊椎动物属的异源副肌球蛋白均无保护作用，这表明免疫中需要特定表位。抗副肌球蛋白抗体不能将显著的抗感染抗性被动转移给受体小鼠，这支持了副肌球蛋白诱导的保护涉及T细胞介导机制的观点。发现接种副肌球蛋白小鼠的淋巴细胞在接触活的血吸虫幼虫时会产生IFN - γ，这表明在接种疫苗宿主的攻击感染期间，副肌球蛋白（一种非表面抗原）可能由于其从迁移的寄生虫幼虫中释放而引发保护性T细胞反应。还发现去除副肌球蛋白的SWAP对来自接种SWAP小鼠的T淋巴细胞具有保护作用和刺激作用，这表明该制剂中的其他抗原可能具有免疫预防潜力。总之，这些结果（i）表明诱导针对可溶性非表面抗原的T细胞依赖性细胞介导免疫可能是针对多细胞寄生虫免疫的有效策略，（ii）就血吸虫而言，确定副肌球蛋白为这类候选疫苗免疫原。
