Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

196份恙虫病患者血清IgM抗体分析

采用斑点酶标染色技术对临床疑似恙虫病患者196份血清进行了IgM抗体的检测并作了初步统计分析。总检出率为92.3%；病后3天内检出率为50%，抗体滴度几何平均值（GMT）为226；4-7天检出率为83%，GMT为320；第4周抗体滴度达峰值，GMT为1585，检出率为100%，同时在4周内棋 GMT与发病时间呈正相关。提示应用本法进行IgM抗体的检测对恙虫病的早期诊断和流行病学调查有着重要意义。     

5例孕妇梅毒临床分析

目的:了解孕妇梅毒感染率,制定相应的预防措施。方法:对469例建立围产期保健卡的孕妇进行梅毒螺旋体快速血浆反应试验(RPR),阳性者再进行梅毒补体试验确诊(TPPA)。结果:5例孕妇确诊梅毒感染,感染率为1·07%。结论:孕期开展RPR筛查十分必要。     

RPR与TPHA法检测梅毒螺旋体的比较与应用

梅毒螺旋体存在于病人的血液或脑脊液内 ,在人工培养基或组织培养中不能生长。当梅毒螺旋体进入人体 3～ 6周后 ,可在病人血清中检测出两种抗体 ,一种是针对非螺旋体抗原的抗体 ,应用ＲＰＲ试验 (ｒａｐｉｄｐｌａｓｍａｒｅｇａｉｎｃｉｒｄｅｃａｒｄｔｅｓｔ快速血浆反应素环状卡片试验 )检测 ;另一种是针对螺旋体抗原的抗体 ,应用ＴＰＨＡ试验 (ｔｒｅｐｏｎｅｍａｐａｌｉｄｕｍｈｅｍａｇｇｌｕｔｉｎａｔｉｏｎａｓｓａｙ)检测。本文就 2 0 0 0年 9月～ 2 0 0 1年9月在我院检验结果进行分析现报告如下。1　材料与方法1 1　检测对象2 …     

Encephalomyocarditis (EMC) virus-induced sialodacryoadenitis in mice

The mode of occurrence of the D variant of encephalomyocarditis (EMC-D) virus-induced acute sialodacryoadenitis was investigated using three strains of mice differing in their sensitivity to EMC-D virus-induced diabetes (C57BL/6: resistant; BALB/c: moderately sensitive; DBA/2: highly sensitive). Mice were intranasally inoculated with high (10(5) PFU/mouse) or low dose (10(2) PFU/mouse) of EMC-D virus. Although there were individual differences, the blood virus titer generally reached the peak earlier in the high-dose group than in the low-dose group. Signals of viral RNA and histopathological changes were seen in parotid glands and intraorbital and extraorbital lachrymal glands. In these glands, signals of viral RNA and histopathological changes were detected only in acinar cells and initial lesions were characterized by pyknosis of acinar cells. Coagulative necrosis with interstitial inflammatory cell infiltration developed later in parotid glands of BALB/c mice of the high-dose group and in intraorbital and extraorbital lachrymal glands of all groups except for C57BL/6 mice of the low-dose group. Such changes were not observed in epithelial cells of the ductal system. The present results indicate that EMC-D virus shows clear tissue and cell tropism within the salivary and lachrymal glands, probably due to the distribution of receptors for EMC virus.     

微量法测定血清杀菌效价的临床应用

目的 :评价血清杀菌效价测定对指导临床用药的意义。方法 :应用改进设计的一种微量法测定血清杀菌效价 2 0例次 ,查阅病历 17份 ,典型病例分析 3例。结果 :峰时、谷时均有一定杀菌效价。 17例各种抗感染 ,包括耐药菌感染、复杂病例均有效。峰时杀菌效价一般以 1∶8为宜 ,<1∶8临床也有效。抑菌效价与杀菌效价有一定的相关性。结论 :能适时客观地反映体内综合的杀菌效果 ,指导临床合理用药。     

国产重组(酵母)乙型肝炎疫苗的免疫动力学研究

目的　评价国产重组(酵母)乙型肝炎(乙肝)疫苗(YDV)的免疫学效果,建立免疫动力学模型,以预测国产YDV的免疫持久性,为初次免疫后何时进行加强免疫提供参考依据。方法　采用队列研究的方法,对接种国产YDV者的乙肝病毒表面抗体(抗HBs)滴度进行了5年的追踪观察。利用曲线拟合方法建立免疫动力学模型,并对其免疫持久性进行预测。在接种疫苗后第8年,再次对研究队列进行抗 HBs滴度实际测定,以检验模型预测结果的可靠性。结果　接种YDV5年后,抗HBs阳性率由接种后第1年的10 0 %下降到73% ,抗 HBs几何平均滴度(GMT)由接种后第1年的16 0mIU/ml下降到5 3mIU/ml。到第8年时,实际测定值下降到35mIU/ml,所拟合的模型为Y =16 5 . 6 7exp(- 0 .0 19X) ,决定系数R2 为0 . 98,模型预测的结果为2 7mIU/ml,比实际值低8mIU/ml。结论　按照模型预测的结果,接种国产YDV 12年后,其抗 HBsGMT为10 74mIU/ml,仍维持在10mIU/ml的保护性水平以上。由于在第8年时,模型预测值低于实际测定值,因此国产YDV的抗HBsGMT至少可维持12年的预测结果有一定的可靠性。     

管碟法测定抗生素效价中的影响因素分析及对策

目的提高管碟法测定抗生素效价的准确性。 方法按操作步骤逐步分析，并提出合理的解决方案。 结果减少外界因素与人为因素给试验带来的误差。 结论可以提高测定结果的准确性。     

Safety and immunogenicity of a quadrivalent inactivated subunit non-adjuvanted influenza vaccine: A randomized,double-blind,active-controlled phase 1 clinical trial

Quadrivalent influenza inactivated vaccine (IIV4) is more likely to provide wider protection against yearly circulating influenza viruses than trivalent inactivated influenza vaccine (IIV3). In this study, a total of 320 participants were allocated to four age cohorts (6–35 months, 3–8 years, 9–17 years, and ≥ 18 years; 80 participants/cohort) according to their actual date of birth. Participants in each cohort were randomly assigned to two groups to receive intramuscular injection of the trial vaccine or the comparative vaccine in a one-dose (3–8 years, 9–17 years,and ≥ 18 years) schedule on day 0 or two-dose (6–35 months cohort) schedule on day 0 and 28. The first objective is to evaluate the safety and immunogenicity of the full-dose subunit non-adjuvanted IIV4 (FD-subunit NAIIV4) we developed versus an active-control, China-licensed split-virion NAIIV4, in people ≥ 3 years. The second objective is to evaluate the safety and immunogenicity of FD-subunit NAIIV4 versus the half-dose (HD-subunit NAIIV4) in toddlers aged 6–35 months. Results showed that all adverse reactions noted were rare, mild, and self-limited. In ≥ 3 years cohorts, systemic adverse reactions in FD-subunit NAIIV4 groups were less than the active control split-virion NAIIV4 groups ([Systemic adverse reaction rates (95%CI)], 15.0 (8.6–21.4) versus 19.2(12.1–26.2), p = 0.391). The overall seroprotection efficacy after vaccination were comparable between FD-subunit NAIIV4 and the active control split-virion NAIIV4([Seroprotection rates (95%CI)], H1N1, 99.2(81.3–100.0) versus 94.9(90.9–98.9), p = 0.117; H3N2, 81.7(74.7–88.6) versus 82.1(75.1–89.0), p = 0.939; BV, 75.8(68.2–83.5) versus 74.4(66.4–82.3), p = 0.793; BY, 94.2(90.0–98.4) versus 92.3(87.5–97.1), p = 0.568). Additionally, FD-subunit NAIIV4 has comparable safety and better seroprotection versus that of the half-dose in 6–35 months toddlers groups ([Total adverse reaction rates (95%CI)], 37.5(18.5–56.5) versus 47.5(26.1–68.9), p = 0.366) ([Seroprotection rates (95%CI)], H1N1, 85(56.4–100.0) versus 75.7(47.6–100.0), p = 0.117; H3N2, 50(28.1–71.9) versus 29.7(12.2–47.3), p = 0.070; BV, 75(48.2–100.0) versus 29.7(12.2–47.3), p < 0.001; BY, 75(48.2–100.0) versus 56.8(32.5–81.0), p = 0.091). As a result, the FD-subunit NAIIV4 we developed is safe and effective to provide broader and adequate protection against the circulating influenza viruses during 2018–2019, which could be an essential component of the global preventive strategy for influenza pandemic.