广谱肾综合征出血热病毒单克隆抗体的A35的生物学性状

具有中和及血凝抑制活性的、能和世界各地分离到的肾综合征出血热病毒(HFRSV)发生反应的、广谱的单克隆抗体(McAb),对HFRSV的诊断和分子生物学研究都有重要意义。 本文着重比较了HFRSV McAbA5、A19、A25-1、A25-7和A35的生物学性状,并观察了对感染动物的实验治疗效果。     

The role of L3T4+ and Lyt-2+ T cells in the IgE response and immunity to Nippostrongylus brasiliensis

The role of L3T4+ and Lyt-2+ T cells in protective immunity to Nippostrongylus brasiliensis (Nb) was studied in BALB/c mice that were depleted of either the L3T4+ or Lyt-2+ T cell population by injection with rat mAb specific for the appropriate determinant. Host responses to Nb infection including spontaneous elimination of adult worms, development of intestinal mucosal mast cell hyperplasia and the generation of a polyclonal IgE response were all completely blocked by 0.5 mg anti-L3T4 antibody administered simultaneously with Nb inoculation. However, administration of 0.5 mg of anti-Lyt-2 antibody at the same time and 7 days after inoculation with Nb had no effect on any of these responses. Injection of anti-L3T4 antibody as late as 9 days after Nb inoculation interfered with spontaneous cure of Nb infection and anti-L3T4 antibody injection 11 days after Nb inoculation inhibited serum IgE levels measured on day 13 by 50%. In addition, administration of anti-L3T4 antibody at the time of the peak serum IgE response, 13 days after Nb inoculation, accelerated the decline in serum IgE levels. Injection of previously Nb-infected mice with anti-L3T4 antibody at the time of a second Nb inoculation prevented the development of a secondary IgE response but did not affect immunity to Nb infection based on finding no adult worms in the intestines of these mice. These data indicate that 1) L3T4+ T cells are required for spontaneous cure of Nb infection, development of intestinal mucosal mast cell hyperplasia, and the generation and persistence of an IgE response during primary infection with Nb and 2) L3T4+ T cells are required for a considerable time after inoculation for optimal development of these responses. However, L3T4+ T cells are not required for all protective responses in immune mice. In contrast, our data indicate that considerable depletion of the Lyt-2+ T cell population has no significant effect on either worm expulsion or the generation of serum IgE responses.     

Protective effect of measles virus inoculation on subacute sclerosing panencephalitis virus-infected mice

The Biken strain of subacute sclerosing panencephalitis (SSPE) virus caused a fatal neurologic disease in adult mice after intracerebral inoculation. However, the mice were completely protected from the disease when a high dose of measles virus was given intracerebrally after the SSPE virus infection. The measles virus inoculation induced interferon production and immune responses. An experiment with athymic nude mice showed that interferon and anti-measles antibody were able to prolong the incubation period of the disease but not to protect the SSPE virus-infected nude mice from death. For complete protection, T lymphocytes appeared to be essential. The present study suggested that the protective effect of measles virus inoculation is basically due to the induction of immune responses and that SSPE virus infection in mice is susceptible to immune reactions.     

The effect of Bordetella pertussis lymphocytosis-promoting factor (LPF) on antibody response in mice: its enhancing and suppressive effects

The effect of lymphocytosis-promoting factor (LPF) on antibody response in mice was estimated under different sets of experimental conditions. Four- and 6-week-old mice were intravenously inoculated with LPF. Three days later these mice were inoculated either intraperitoneally or intravenously with sheep red blood cell (SRBC) or human serum albumin (HSA) as an antigen. The adjuvant effect of LPF was demonstrated on antibody response in 6-week old mice to intraperitoneally inoculated SRBC but not to intravenously-inoculated one. When 4-week-old mice were immunized, hemagglutinin production in response to intraperitoneally inoculated SRBC was not enhanced by LPF. In addition, a rather suppressive effect of LPF at a comparatively high dose was demonstrated on hemagglutinin production in response to intravenously inoculated SRBC. Anti-HSA production was enhanced by inoculation of LPF in any combination of the mouse age and the route of antigen administration. These findings indicate that the adjuvant effect of LPF on antibody response in mice depends upon experimental conditions: the age of mice, the quality of antigen and the route of antigen administration used for immunization.     

Effect of nonspecific immune stimulation with BCG and polidin on the Ehrlich ascites tumor growth

Investigations were performed to study: 1) the antitumor effect of BCG pretreatment on the development of Ehrlich ascites tumor in mice; 2) the effect of BCG administration in relation to the period of time before tumor inoculation and the dose levels used, and 3) the antitumor effect of an associated pretreatment of BCG and Polidin on the development of Ehrlich ascites tumor. BCG administered prior to Ehrlich ascites tumor inoculation have a protective effect evidenced by a delay in tumor development, a prolonged survival of the tumor host and, in some cases, even inhibition of tumor growth. The effect of BCG was highly dependent on 1) the dose and the time of administration of BCG and) 2 the combined pretreatment of BCG and Polidin.     

甲型H1N1流感病毒佐剂疫苗小鼠免疫效果

为了探讨甲型H1N1流感病毒氢氧化铝佐剂疫苗对小鼠的免疫作用及对小鼠繁殖性能的影响,以不同剂量、不同免疫程序免疫小鼠后定期采血;用血凝抑制(HI)方法检测血清H1N1流感病毒HI抗体滴度,观察H1N1流感病毒佐剂疫苗对小鼠受孕、产仔、哺乳的影响;比较孕鼠及非孕鼠的抗体滴度,免疫后孕鼠所产仔鼠的体重及H1N1胎传抗体水平。结果显示,以0.5μg组开始的不同剂量、不同免疫程序均可使小鼠产生90倍以上水平的H1N1流感病毒抗体;免疫后的小鼠不影响受孕、产仔及哺乳;仔鼠保护性抗体可持续1个月以上。H1N1流感病毒佐剂疫苗是一种高免疫原性的制剂,用低剂量免疫,即可产生90倍以上持续时间较长的保护性抗体。这种佐剂疫苗对小鼠的繁殖性能无明显影响,免疫产生的抗体经胎盘可垂直传递给仔鼠。     

Anti-tumour effect of humoral and cellular immunities mediated by a bacterial immunopotentiator,Lactobacillus casei,in mice

Summary Administration of a mixture containing Lactobacillus casei YIT 9018 (LC9018) and methylcholanthrene-induced fibrosarcoma (Meth A) cells into the peritoneum of syngeneic BALB/c mice suppressed the tumour growth and protected the mice from tumour death. With the appearance of the anti-tumour activity, serum complement-dependent tumour cytotoxic (CDC) antibody was induced on the 5th day after the administration as a result of the adjuvant effect. The cytotoxic antibody was not found in serum on the 5th day after inoculation of Meth A cells alone, but it was induced before the mice died of the tumours. Adjuvant induction of the cytotoxic serum antibody at an early time was also observed using Kirsten murine sarcoma virus-transformed tumour (K234) cells. Both of these cytotoxic antibodies in sera from Meth A-suppressed and the tumour-bearing mice were specific for the tumour cells and were IgM class, since they were absorbed with rabbit anti-mouse IgM antibody. However, the cytotoxic antibody was not found in the peritoneal cavity which was the tumour inoculation site, but binding antibody against the tumour cells was faintly detected in the region using an enzyme-linked immunoabsorbent assay (ELISA). In neutralization tests, the cytotoxic antibody did not exert anti-tumour activity in recipient mice when it was administered to the mice along with the tumour cells or when it was administered i. v. at the time of tumour inoculation. Moreover, the cytotoxic antibody was not available for the antibody-dependent cell-mediated cytotoxicity (ADCC). These results suggest that the cytotoxic antibody did not exert anti-tumour activity in the tumour-suppressed mice. In contrast, peritoneal exudate cells (PEC) on the 5th day, and PEC and spleen cells on the 15th day after i. p. administration of the mixture exerted strong anti-tumour activity as measured by the Winn test.In conclusion, the adjuvant effect of LC9018 induced tumour-specific humoral and cellular immunities but the anti-tumour activity was dependent only on the cellular effectors of the host. The possible use of LC9018 in tumour immunotherapy is discussed.     

Radioprotective efficacy of tocopherol succinate is mediated through granulocyte-colony stimulating factor

The purpose of this study was to elucidate the role of granulocyte colony-stimulating factor (G-CSF) induced by α-tocopherol succinate (TS) in protecting mice from total-body irradiation. CD2F1 mice were injected with a radioprotective dose of TS and the levels of cytokine in serum induced by TS were determined by multiplex Luminex. Neutralization of G-CSF was accomplished by administration of a G-CSF antibody and confirmed by cytokine analysis. The role of G-CSF on gastrointestinal tissue protection afforded by TS after irradiation (11 Gy, 0.6 Gy/min of ⁶⁰Co γ-radiation) was determined by analysis of jejunum histopathology for crypt, villi, mitotic figures, apoptosis, and cell proliferation. Our results demonstrate that TS protected mice against high doses of radiation-induced gastrointestinal damage and TS also induced very high levels of G-CSF and keratinocyte-derived chemokine (KC) production in peripheral blood 24 h after subcutaneous administration. When TS-injected mice were administered a neutralizing antibody to G-CSF, there was complete neutralization of G-CSF in circulating blood, and the protective effect of TS was significantly abrogated by G-CSF antibody. Histopathology of jejunum from TS-injected and irradiated mice demonstrated protection of gastrointestinal tissue, yet the protection was abrogated by administration of a G-CSF antibody. In conclusion, our current study suggests that induction of G-CSF resulting from TS administration is responsible for protection from ⁶⁰Co γ-radiation injury.     

单克隆抗体对感染流行性感冒病毒的小鼠的疗效观察

治疗流行性感冒(简称流感)对年老体弱者有着重要意义。由于流感病毒的一个新亚型出现后,往往要经历十几年至20多年的流行,因此选出具有亚型内共同抗原决定簇的McAb,用于治疗流感是可行的,文献也曾有过报道。前文已报道关于甲3型流感病毒McAb的建立,本文用抗甲3型流感病毒上海/32/84血凝素McAb,与1977年以来分离的甲3型流感     

Induction of effective immunity to Moloney murine sarcoma virus using monoclonal anti-idiotypic antibody as immunogen

We have isolated an anti-idiotypic mAb (RS1.1.3), which recognizes an idiotope present on several IgM mAb specific for Moloney murine leukemia virus (M-MuLV)-determined cell surface Ag. The binding of RS1.1.3 to idiotypic antibody could be inhibited by specific Ag. Intraperitoneal immunization of mice with purified RS1.1.3 antibody-induced effective immunity against Moloney murine sarcoma virus challenge. A single injection of RS1.1.3 7 days before virus challenge resulted in a 27% reduction in tumor load compared to non-immune control mice challenged with the same dose of virus, whereas multiple injections of RS1.1.3 before virus challenge resulted in a 75% reduction in tumor load. The protective effect of anti-idiotype immunization appeared to be T dependent, because immunization of athymic mice had no effect on their susceptibility to tumor virus challenge. Administration of the anti-idiotypic antibody after virus inoculation caused an increase in tumor load of nearly 50% compared to non-immune controls. BALB/c mice immunized with RS1.1.3 developed anti-anti-idiotypic antibodies, as well as M-MuLV Ag-specific antibodies. Analysis of sera from RS1.1.3-immune mice subsequently challenged with Moloney murine sarcoma virus indicated an inverse relationship between tumor load and M-MuLV-specific serum IgG titers induced by the RS1.1.3 immunization. These results indicate that anti-idiotypic mAb may be used as immunogen to induce Ag-specific antibody responses, and to cause effective immunity to a retro-virus-induced tumor.