Two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against Zika virus infection in rhesus macaques

Zika virus (ZIKV) infection has caused major public health problems recently. To develop subunit vaccines for ZIKV, we have previously constructed recombinant ZIKV envelope protein domain III (EDIII), and the entire ectodomain (E80, which comprises EDI, EDII and EDIII), as vaccine candidates and showed both of them being immunogenic and protective in murine models. In this follow-up study, we compared these vaccine candidates in non-human primates. Both of them elicited neutralizing antibody responses, but only E80 immunization inhibited ZIKV infection in both peripheral blood and monkey tissues, whereas EDIII increased blood ZIKV RNA through possibly antibody-dependent enhancement. Further investigations revealed that the virion-binding antibody response in E80 immunized monkeys persisted longer and stronger than in EDIII immunized monkeys. These results demonstrate that E80 is superior to EDIII as a vaccine candidate, and that the magnitude, quality and durability of virion-binding neutralizing antibodies are correlates of protection.     

1990—2019年中国丙型病毒性肝炎疾病负担评估

目的 分析1990—2019年中国丙型病毒性肝炎疾病负担变化趋势与流行现状,为推动消除丙型病毒性肝炎行动提供科学依据。方法 利用2019全球疾病负担研究(GBD 2019)数据,分析中国人群丙型病毒性肝炎发病、患病、伤残调整生命年(DALY)及寿命损失年(YLL)的30年变化趋势与现状,应用GraphPad Prism 8.0作图。结果 2019年,中国丙型病毒性肝炎疾病总负担之标化DALY率约101/10万人年;急性丙型病毒性肝炎标化发病率约47/10万;丙型病毒性肝炎相关慢性肝病的发病率高峰在40～44岁,标化患病率约1 247/10万。1990—2019年,丙型病毒性肝炎总标化发病率和标化患病率均于2015年降到波谷,之后4年急转上升;标化DALY率30年持续下降。结论 丙型病毒性肝炎疾病负担以丙型病毒性肝炎相关慢性肝病为主;因直接抗病毒药物治疗周期短、疗效好,建议加大宣传力度,加强丙型病毒性肝炎筛查,推进健康中国建设。     

Genetic characterization and recombinant history of a novel HIV-1 circulating recombinant form (CRF101_01B) identified in Yunnan,China

The high frequency of multiple HIV-1 recombinant events among the B, C and CRF01_AE were constantly occurring in Yunnan China. Here, we characterized a novel HIV-1 circulating recombinant form (CRF) consisting of CRF01_AE and subtype B (CRF101_01B) from three epidemiologically unlinked individuals. Phylogenetic analysis based on near full length genome (NFLG) sequences revealed that CRF101_01B formed a distinct monophyletic cluster supported by a high bootstrap value of 100%, distantly related to all known HIV-1 CRFs. CRF101_01B had a CRF01_AE backbone with two B segments inserted, respectively, in the gag and pol region. Further, subregion tree analysis showed that CRF01_AE backbone and subtype B segment inserted originated from a Thailand lineage. In addition, our study found that CRF101_01B originated around the year 1996–1998. This findings described a novel HIV-1 CRF, and highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in Yunnan, China.     

Specificity of tuberculin skin test improved by BCG immunization schedule change in Japan

IntroductionTuberculin skin test (TST) has been used to diagnose tuberculosis (TB) and latent tuberculosis infection (LTBI). However, in Bacillus Calmette-Guérin (BCG) vaccinated patients, TST tends to produce false-positive results. According to the previous vaccination schedule, Japanese people were mandated to receive up to three doses of BCG-vaccine. The vaccination schedule was changed in 2003 and as per the new schedule, only infants are administered a dose of BCG vaccine. Our hypothesis is that this change can lead to a reduction in the cross-reaction to TST.MethodsWe evaluated the TST results obtained from 1097 recruits from six defense camps and 667 recruits from an air base. These TST data were divided into two groups according to the date of birth: a new group and an old group according to the BCG immunization schedule. We then analyzed positive and negative reaction of TST and erythema sizes.ResultsWe confirmed that the change in BCG-vaccination schedule significantly decreased TST false-positive reaction (P_meta = 1.4 × 10⁻¹⁸; risk ratio = 0.83; 95% confidence interval: 0.80–0.87) and erythema size (P_meta = 1.1 × 10⁻⁴; mean difference = 6.6 mm; 95% confidence interval: 3.2 mm–9.9 mm).ConclusionsWe showed the reduction in BCG cross-reaction to TST, in the new BCG vaccination schedule group, compared to the old group, we also have extracted information on the improvement in the specificity of TST for LTBI and TB diagnosis, which resulted from BCG schedule change.     

A novel nutritional index and adverse outcomes in ischemic stroke: Results from the third China National Stroke Registry

Background and aimsFew studies have applied the triglyceride, cholesterol, body weight index (TCBI) in acute ischemic stroke (AIS). We investigated the association between the TCBI and adverse clinical outcomes in patients with AIS.Methods and resultsBased on the Third China National Stroke Registry (CNSR-III) data from August 2015 to March 2018, we evaluated the nutritional status of patients with AIS using the TCBI. Patients were categorized according to quartile levels of the TCBI. The main outcomes were poor functional outcomes and recurrent stroke at 1-year and secondary outcomes were adverse outcomes at 3 and 6 months after stroke onset. Poor functional outcomes consisted of all-cause mortality and major disabilities. Multivariate analyses with logistic or Cox regression analysis and restricted cubic splines determined the association between the TCBI and adverse outcomes. We included 9708 patients. At the 1-year follow-up, 1323 patients (13.6%) had died or experienced major disability. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the lowest quartile at 1-year were 1.47 (1.22–1.78) for poor functional outcomes, 1.46 (1.18–1.81) for major disability, and 1.34 (0.94–1.86) for all-cause mortality. Kaplan–Meier analysis demonstrated an inverse relationship between all-cause mortality and the TCBI (log-rank p < 0.05). An approximately L-shaped relationship between TCBI levels and poor functional outcomes and major disability was observed at 1-year.ConclusionThe novel TCBI was associated with short- and long-term adverse outcomes in AIS. Thus, it may be useful for predicting adverse outcomes in patients with AIS.     

Are refugees arriving in Denmark an under-immunised group for measles? A cross-sectional serology study

BackgroundIn 2018, Europe faced the highest number of Measles cases in a decade. In Denmark, the childhood vaccination programme has a coverage of approximately 90%. To eliminate the disease, vaccine coverage needs to be above the herd immunity threshold of 95%. This can be even more difficult to obtain, when vaccination programmes break down due to war, natural disasters etc. and concern has been raised, that unvaccinated refugees could facilitate spread of measles when migrating.MethodsIn order to address this concern, we tested 513 newly arrived refugees and family reunified refugees aged between 0 and 70 years for measles IgG antibodies. The participants were tested as part of a general health assessment between May 2016 and October 2018. In the cohort, 50% were males and the majority came from Syria (55%).ResultsWe found that 85% of the total group of refugees had immunity against measles. The 15% lacking antibodies were evenly distributed between the various countries of origin. Moreover, we found immunity to increase with age, leaving young children most vulnerable to infection, 79.9% (<19 years) vs 89.1% (≥19 years). Interview questions on previous vaccinations did not correlate to serology.ConclusionRefugees have measles immunity slightly lower than the host population.     

HIV确诊后尽早启动治疗可能减少患者脱失

目的  分析从人类免疫缺陷病毒(human immunodeficiency virus, HIV)确诊到启动治疗时间间隔对艾滋病抗病毒治疗中患者脱失的影响,为指导动员治疗咨询提供参考。 方法  对云南省15年艾滋病抗病毒治疗(antiretroviral therapy, ART)数据回顾性分析,用COX回归评估不同时间间隔组患者首次发生脱失的风险。 结果  2004年-2018年在云南省接受ART的110 373例HIV感染者纳入分析,从HIV确诊到启动ART时间中位数47(11,550) d,中位随访2.63(0.88,5.28)年。其中47 974例(43.5%)患者在确诊HIV后30 d内启动ART,15 811例(14.3%)间隔时间在31~90 d,14 253(12.9%)例间隔时间在91~365 d,32 335例(29.3%)间隔时间超过365 d。总脱失率为6.77/100人年(95% CI：6.69~6.85)。以 < 30 d组为参照,30~ d组、91~ d组、>365 d组发生脱失的风险分别提高了10%、22%和14%。 < 30 d组、30~ d组、91~ d组、>365 d组患者治疗1年累计脱失率分别为11.4%、12.7%、15.0%和15.7%。 结论  通过真实世界数据证实：缩短从HIV确诊到启动ART时间间隔(30 d内)可以减少治疗中脱失。研究结果支持“艾滋病检测与治疗一站式服务”作为防治措施实施,并为云南省指导动员治疗咨询提供建议。     

Immunization with lipopolysaccharide-free outer membrane complexes protects against Acinetobacter baumannii infection

Outer membrane complex (OMC) vaccines, which contain antigens from the bacterial outer membrane, have been developed for multiple Gram-negative bacteria. However, OMC vaccines demonstrate high endotoxin activity due to the presence of lipopolysaccharide in the bacterial outer membrane, thus precluding their use in humans. We isolated OMCs from an LPS-deficient strain of A. baumannii (IB010) which completely lacks LPS due to a mutation in the lpxD gene. OMCs from IB010 demonstrated a more than 10,000-fold reduction in endotoxin activity compared to OMCs from wild type A. baumannii. Vaccination with IB010 OMCs produced similar levels of antigen-specific IgG and IgM after two administrations compared to wild type OMCs, and resulted in a similar reduction in post-infection spleen bacterial loads and serum pro-inflammatory cytokine levels. Vaccination with IB010 OMCs provided significant protection against infection compared to control mice, indicating the LPS-free OMCs could contribute to vaccine strategies for preventing infection by A. baumannii.