风疹减毒活疫苗主种子批毒种(松叶株)的安全性和免疫原性检测

评价兰州生物制品研究所用风疹病毒松叶株主种子批毒种制备的冻干风疹减毒活疫苗的安全性和免疫原性。采用自身对照、开放性的免疫原性临床观察试验,对100名8～10月龄筛选后符合条件的健康易感儿童,皮下接种1剂风疹减毒活疫苗,观察其免疫后的局部和全身反应并采集每个受试者免前和免后35d的血清标本,检测风疹HI抗体,计算阳转率和几何平均滴度。试验中所有受试者在系统观察期内均未观察到注射部位局部的不良反应;总的发热率为5%,且均为轻度发热;有1例在观察期内出现腹泻和咳嗽并持续5d,发生率为1%,属中度全身反应;血清风疹病毒抗体(HI)阳转率为100%,GMT为1:638.7±1.7。该疫苗与国内、外其它种类的风疹疫苗一样具有良好的安全性和免疫原性。     

Immunization of acute leukemic children with a live varicella vaccine (Oka strain)

A total of 52 acute leukemic children have been safely and effectively vaccinated with live varicella (Oka strain) vaccine given under close clinical and immunological observation. The incidence of zoster in the vaccinated children group was slightly less than that in the group that had experienced natural varicella.     

Evaluation of live trivalent vaccine of measles AIK-C strain, mumps Hoshino strain and rubella Takahashi strain, by virus-specific interferon-gamma production and antibody response

A trivalent measles-mumps-rubella live virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was evaluated in 229 children, aged 1 to 5 years. The vaccine induced a high seroconversion rate: 221 (98.7%) out of 224 subjects initially seronegative for measles virus, 167 (93.3%) out of 179 initially seronegative for mumps virus, and 212 (99.1%) out of 214 initially seronegative for rubella virus. It also induced a sufficient cellular immunity against each of the three viruses in over 90% of the subjects, as judged by virus-specific interferon-gamma (IFN-gamma) production. Virus-specific IFN-gamma production was observed 10 days after vaccination by stimulation with measles virus and rubella virus and 14 days after vaccination by stimulation with mumps virus. Mumps-virus-specific IFN-gamma production was observed in 7 out of 12 recipients without seroconversion for mumps virus. And measles-virus-specific IFN-gamma production was demonstrated in one out of three recipients without seroconversion for measles virus. A significant correlation was observed between the serum antibody and IFN-gamma production six weeks after vaccination for measles virus (r = 0.201, P less than 0.01) and for mumps virus (r = 0.174, P less than 0.05) but not for rubella virus (r = -0.045, P less than 0.05). The incidence of febrile reactions of greater than or equal to 37.5 C was quite low, 14.4%, and that of greater than or equal to 39 C occurred in only 1.3% of the recipients. These results suggested that the trivalent vaccine induced sufficient humoral and cellular immunity and yet resulted in no more untoward reaction than observed from the measles vaccine alone.     

Development and characterization of a live varicella vaccine (Oka strain)

A live varicella vaccine (Oka strain) was developed by serial passage of the Oka strain isolated in our laboratory, in human embryonic lung cells (11 times at 34 C) and guinea pig embryo cells (12 times at 37 C). It is slightly temperature sensitive at 39 C and shows a higher ratio of infectivity in guinea pig embryo cells to infectivity in human embryo cells than wild-type strains. The DNA digest with Hpa I enzyme of the Oka strain contained one unique fragment (K), although its mobility differed only slightly from that of the corresponding fragment of wild-type strains. Studies with clinical varicella zoster virus (VZV) isolates from vaccinees indicated that tests on the ratio of infectivity in guinea pig embryo fibroblasts (GPEF) to that in human embryo fibroblasts (HuEF) and the profile of the DNA digest with Hpa I are useful for differentiation of the vaccine strain from wild-type strains. The vaccine virus showed stable immunogenicity during at least 15 further repeated passages in human diploid cells, a character which seems helpful for production of a large quantity of vaccine virus for practical use.     

Characteristics of the immune response of children in the Arctic to live measles vaccine

The intensity of immune response to live measles vaccine varies in children living in different climatic and geographical regions. The least intensive immunogenesis is registered in children living in the Arctic regions. The level of seroconversion in children living in these regions rises in response to measles vaccine containing a 10-fold amount of the virus per immunization dose.     

Studies on live rubella vaccine. VI. Seroepidemiological surveillance and immunization of adolescents in high school.

The rubella seroimmunity status of a total of 1,204 students aged 12 to 19 in a junior and a senior high school in Osaka district was surveyed. Among these, 487 students (40.5%) were found to be seronegative (less than 1 : 8) by the hemagglutination inhibition (HI) test. A total of 287 students were immunized with live rubella vaccine, Biken lot No.7233. This caused an increased titer in all except one of the 262 seronegative students, while among 25 students with an initial HI antibody titer of 1 : 8 it caused more than 4-fold increase in 20 and 2-fold increase in 5. The vaccine caused no clinical manifestations, such as fever, rash or arthralgia.     

Clinical application of a live varicella vaccine (Oka strain) in a hospital

A total of 239 children, including 22 high-risk children and 55 non-high risk diseased children have been immunized with a live varicella vaccine (Oka strain) since June, 1978. No clinical reaction attributable to the vaccine has been observed. Of these children, 87 received emergency vaccination. Of 47 children receiving emergency vaccination because they had been in contact with varicella patients either in hospital, school or a playground, only 5 developed varicella and their symptoms were mild. Of 40 children receiving emergency vaccination because of exposure to varicella in their home, 10 developed mild varicella and 30 were protected. Clinical symptoms of varicella when seen seemed to be due to incomplete protection because the vaccine was given too late rather than to clinical reactions to the vaccine. During follow-up period of 6 to 66 months after vaccination, 8 children showed very mild rashes without fever as the result of exogenous varicella infection.     

Macrophage proinflammatory response to Francisella tularensis live vaccine strain requires coordination of multiple signaling pathways

The macrophage proinflammatory response to Francisella tularensis (Ft) live vaccine strain (LVS) was shown previously to be TLR2 dependent. The observation that intracellular Ft LVS colocalizes with TLR2 and MyD88 inside macrophages suggested that Ft LVS might signal from within the phagosome. Macrophages infected with LVSDeltaiglC, a Ft LVS mutant that fails to escape from the phagosome, displayed greatly increased expression of a subset of TLR2-dependent, proinflammatory genes (e.g., Tnf) but decreased expression of others (e.g., Ifnb1). This latter subset was similarly mitigated in IFN-beta(-/-) macrophages indicating that while Ft LVS-induced TLR2 signaling is necessary, cytosolic sensing of Ft to induce IFN-beta is required for full induction of the macrophage proinflammatory response. Although LVSDeltaiglC greatly increased IL-1beta mRNA in wild-type macrophages, protein secretion was not observed. IL-1beta secretion was also diminished in Ft LVS-infected IFN-beta(-/-) macrophages. rIFN-beta failed to restore IL-1beta secretion in LVSDeltaiglC-infected macrophages, suggesting that signals in addition to IFN-beta are required for assembly of the inflammasome and activation of caspase-1. IFN-beta plays a central role in controlling the macrophage bacterial burden: bacterial recovery was greater in IFN-beta(-/-) than in wild-type macrophages and treatment of Ft LVS-infected macrophages with rIFN-beta or 5,6-dimethylxanthenone-4-acetic acid, a potent IFN-beta inducer, greatly decreased the intracellular Ft LVS burden. In toto, these observations support the hypothesis that the host inflammatory response to Ft LVS is complex and requires engagement of multiple signaling pathways downstream of TLR2 including production of IFN-beta via an unknown cytosolic sensor and activation of the inflammasome.     

冻干风疹活疫苗生产工艺研究

文报告了冻干风疹减毒活疫苗生产工艺及疫苗研制结果。在对日本化学血清疗法研究所疫苗生产株—松叶株全面检定的基础上,通过对原代兔肾细胞培养条件及病毒培养条件的试验优化,建立了疫苗生产工艺并制备出了冻干风疹活疫苗制剂,稳定性试验表明其安全有效、质量稳定可靠,而且其生产工艺切实可行、投入产出率高。     

Clinical trial of the Oka strain of live attenuated varicella vaccine on healthy children

Clinical and serological follow-up studies were made on 257 healthy children who had received live varicella vaccine (strain Oka) in Showa Hospital. Good antibody responses were shown with a seroconversion rate of 98.4% (253/257) by the immune adherence hemagglutination test. Mild adverse reactions were observed in 11 of the vaccinated children. During observation periods of 6 months to 4 years, 6 of the 253 children who were successfully vaccinated contracted mild varicella, while all 4 vaccinees who showed no primary immune response contracted mild to moderate clinical varicella. It is concluded that this vaccine is highly immunogenic and causes few clinical reactions in normal children.     

Studies on live rubella vaccine. V. Quantitative aspects of interference between rubella, measles and mumps viruses in their trivalent vaccine

Rubella vaccine combined with measles and mumps vaccines was administered in a single injection to children of 1 to 5 years of age. All three vaccines were serologically effective, and the clinical reactions caused by measles vaccine were considerably alleviated, when 6 x 10(3) PFU of rubella and 10(4) TCD50 per dose of mumps vaccines were combined with 5 x 10(4) TCD50 of measles vaccine. When a larger amount of mumps vaccine (3 x 10(5) TCD50/dose) was used, it caused interference with the rubella and measles viruses, i.e., the antibody response to rubella virus became poor and the incidence of clinical reactions to measles virus decreased. On the other hand, when 5 x 10(5) TCD50/dose of measles vaccine was combined with 10(4) TCD50/dose of mumps vaccine, the clinical reactions to measles virus were decreased but were almost the same as those induced by this vaccine alone.