Willingness of future A/H7N9 influenza vaccine uptake: A cross-sectional study of Hong Kong community

We conducted a population telephone survey in Hong Kong during the second wave of influenza A/H7N9 outbreak in 2014. Among the respondents, 50.5% of the respondents would like to accept A/H7N9 vaccination in future. Respondents had poor knowledge of A/H7N9 influenza and vaccines. More than 60% of respondents mixed up seasonal influenza this year and A/H7N9 influenza. Results show that socio-demographic factors were all independent of the vaccine uptake willingness while anxiety level and vaccine history were the main affecting factors. Vaccine promotion strategies may focus on influenza knowledge, attitude and behavior.     

人口流动强度与甲型H1N1流感和人感染H7N9禽流感流行的相关性研究

目的 探讨人口流动强度与甲型H1N1流感（简称H1N1）和人感染H7N9禽流感（简称H7N9）的流行关系的模式。方法 利用2009年H1N1监测数据和2013年至2017年2月的H7N9监测数据,采用秩相关、主成分分析、Getis-Ord Gi*热点分析和对应分析探讨人口流动强度与上述两种传染病流行的相关关系。结果 人口流动强度与H1N1和H7N9的发病数均呈正相关。家禽出栏量与H7N9的发病数和人口流动强度也呈正相关。人口流动强度分别与H1N1（〖XC小五号.EPS;P〗=43.40,P<0.0001）和H7N9（〖XC小五号.EPS;P〗=51.82,P=0.0010）的热区位于对应分析图的相同区域,且均存在相同级别的热区聚集在一起,提示人口流动强度与这两种疾病均存在一定的对应关系;家禽出栏量和H7N9的热区位于对应分析图的相同区域,且热区级别大致一一对应,即存在相对严格的对应关系（〖XC小五号.EPS;P〗=36.47,P=0.0140）。人口流动强度与家禽出栏量也存在一定的对应关系,两者的热区位于对应分析图的同一区域（〖XC小五号.EPS;P〗=32.26,P=0.0410）。结论 人口流动强度与H1N1的暴发流行有相关关系,而人口流动强度与H7N9的流行关系是一种典型的“人-物流”的动物源性的传染病模式。     

Live attenuated H7N7 influenza vaccine primes for a vigorous antibody response to inactivated H7N7 influenza vaccine

Background

H7 influenza viruses have emerged as potential pandemic threat. We evaluated the safety and immunogenicity of two candidate H7 pandemic live attenuated influenza vaccines (pLAIV) and their ability to prime for responses to an unadjuvanted H7 pandemic inactivated influenza vaccine (pIIV).

Methods

Healthy seronegative adults received two doses of A/Netherlands/219/03 (H7N7) or one dose of A/chicken/British Columbia/CN-6/04 (H7N3) pLAIV all given as 10^7.5 50% tissue culture infective doses (TCID₅₀) intranasally. A subset of subjects received one 45 μg dose of H7N7 pIIV containing the A/Mallard/Netherlands/12/2000 HA intramuscularly 18–24 months after pLAIV. Viral shedding was assessed by culture and real-time polymerase chain reaction (rRT-PCR), B cell responses following pLAIV were evaluated by ELISPOT and flow cytometry. Serum antibody was assessed by hemagglutination-inhibition (HAI), microneutralization (MN) and ELISA assays after each vaccine.

Results

Serum HAI or MN responses were not detected in any subject following one or two doses of either H7 pLAIV, although some subjects had detectable H7 specific B cells after vaccination. However, 10/13 subjects primed with two doses of H7N7 pLAIV responded to a subsequent dose of the homologous H7N7 pIIV with high titer HAI and MN antibody that cross-reacted with both North American and Eurasian lineage H7 viruses, including H7N9. In contrast, naïve subjects and recipients of a single dose of the mismatched H7N3 pLAIV did not develop HAI or MN antibody after pIIV.

Conclusions

While pLAIVs did not elicit detectable serum MN or HAI antibody, strain-specific pLAIV priming established long term immune memory that was cross-reactive with other H7 influenza strains. Understanding the mechanisms underlying priming by pLAIV may aid in pandemic vaccine development.     

Complete protection against lethal challenge of novel H7N9 virus with heterologous inactivated H7 vaccine in mice

A prototype H7 influenza vaccine constructed based on the H7N7 outbreak in 2003 was tested for the protective efficacy against the novel H7N9 virus in a lethal murine challenge model. Serum samples from vaccinated mice showed significant neutralizing activity against the H7N9 virus and the mice were completely protected with no significant weight loss. The results have direct implications on how to overcome potential vaccine shortage and identify donors for immune sera for passive immunization.     

Safety and immunogenicity of an 8 year interval heterologous prime-boost influenza A/H7N7-H7N9 vaccination

Background

Influenza A/H7N9 viruses are undergoing antigenic drift since their emergence in 2013, and vaccination strategies are needed for pandemic preparedness. Two doses of adjuvanted monovalent inactivated influenza A/H7N9 vaccine (IIV1 A/H7N9) are needed for optimal serological responses. However, administering 2 doses in a pandemic setting might be challenging. We evaluated the immunogenicity of “boosting” with IIV1 A/H7N9 in subjects “primed” 8?years previously with IIV1 A/H7N7.

An Advax-CpG55.2 adjuvanted recombinant hemagglutinin vaccine provides immunity against H7N9 influenza in adult and neonatal mice

There is a major unmet need for strategies to improve the immunogenicity and effectiveness of pandemic influenza vaccines, particularly in poor responder populations such as neonates. Recombinant protein approaches to pandemic influenza offer advantages over more traditional inactivated virus approaches, as they are free of problems such as egg adaptation or need for high level biosecurity containment for manufacture. However, a weakness of recombinant proteins is their low immunogenicity. We asked whether the use of an inulin polysaccharide adjuvant (Advax) alone or combined with a TLR9 agonist (CpG55.2) would enhance the immunogenicity and protection of a recombinant hemagglutinin vaccine against H7N9 influenza (rH7HA), including in neonatal mice. Advax adjuvant induced predominantly IgG1 responses against H7HA, whereas Advax-CpG55.2 adjuvant also induced IgG2a, IgG2b and IgG3 responses, consistent with the TLR9 agonist component inducing a Th1 bias. Advax-CpG55.2 adjuvanted rH7HA induced high serum neutralizing antibody titers in adult mice. In newborns it similarly overcame immune hypo-responsiveness and enhanced serum anti-rH7HA IgG levels in 7-day-old BALB/C and C57BL/6 mice. Immunized adult mice were protected against a lethal H7N9 virus challenge. When formulated with Advax-CpG55.2 adjuvant, greater protection was seen with rH7HA than with inactivated H7 whole virus antigen. Advax-CpG55.2 adjuvanted rH7HA represents a promising influenza vaccine platform for further development.     

甲型H1N1流感疫苗接种对其暴发疫情的影响

目的了解甲型H1N1流感(甲流)疫苗接种后对甲流暴发疫情的影响。方法对2011年4—5月发生在学校的1起甲流暴发疫情进行流行病学描述性分析,用回顾性队列研究的方法分析甲流疫苗接种对该起暴发疫情的影响。结果该校542名师生中191人患病,罹患率为35.24%,发病时间主要集中在4月19—25日,发病人群主要为1～6年级的小学生(χ2=9.972,P0.01),住校生发病高于非住校生,112名接种过甲流疫苗的师生发病率为16.96%,明显低于未接种疫苗的师生(40%),差异有统计学意义(χ2=20.661,P0.05),OR=0.306(95%CI∶0.180～0.521)。结论接种甲流疫苗可以有效预防甲型H1N1流感的发生,减少暴发疫情的发病率。     

一起无防护禽肉加工引起人感染H7N9禽流感病毒的流行病学调查

目的 分析1例人感染高致病性H7N9禽流感病例的感染模式及病原变异情况,为禽流感防控提供依据。方法 采用流行病学方法调查病例可疑暴露史及感染途径,追踪调查病例病情进展;使用核酸检测、病毒分离、基因测序及进化分析等技术对采集的相关标本展开病原学分析。结果 病例无活禽接触史,发病前一周在狭小通风不畅厨房内不带手套加工烹饪光鸡;病例下呼吸道提取物、病家剩余冷冻光鸡表面涂抹标本、活禽来源市场环境标本均检出高度同源的H7N9禽流感病毒,且均在HA基因的裂解位点出现多个碱性氨基酸（PEVPKRKRTAR/GL）插入的突变。结论 无防护禽肉操作是"禽-人"传播模式下的重要感染方式之一,现行的活禽限售区防控措施效果有限,应尽快推进规模化标准养殖,实现活禽全城限售、集中屠宰、冰鲜上市。     

Cross-protection against H7N9 influenza strains using a live-attenuated H7N3 virus vaccine

In 2013, avian H7N9 influenza viruses were detected infecting people in China resulting in high mortality. Influenza H7 vaccines that provide cross-protection against these new viruses are needed until specific H7N9 vaccines are ready to market. In this study, an available H7N3 cold-adapted, temperature sensitive, live attenuated influenza vaccine (LAIV) elicited protective immune responses in ferrets against H7N9 viruses. The H7N3 LAIV administered alone (by intranasal or subcutaneous administration) or in a prime-boost strategy using inactivated H7N9 virus resulted in high HAI titers and protected 100% of the animals against H7N9 challenge. Naïve ferrets passively administered immune serum from H7N3 LAIV infected animals were also protected. In contrast, recombinant HA protein or inactivated viruses did not protect ferrets against challenge and elicited lower antibody titers. Thus, the H7N3 LAIV vaccine was immunogenic in healthy seronegative ferrets and protected these ferrets against the newly emerged H7N9 avian influenza virus.     

四川省阿坝州5例人感染H7N9禽流感病例流行病学特征分析

目的 分析阿坝州2017年人感染H7N9禽流感病例的流行病学特征,为该州制定禽流感预防和控制策略提供依据。方法 对阿坝州2017年报告的5例人感染H7N9禽流感病例按照国家卫生计生委下发的《人感染H7N9禽流感疫情防控方案（第三版）》进行调查,使用Excel 2007、SPSS 17.0进行数据统计分析。结果 阿坝州2017年首次出现人感染H7N9禽流感疫情,共有5例人感染H7N9禽流感确诊病例,死亡3例,病死率为60.00%。男2例,女3例,男女性别比为0.67∶1。其中,最小年龄51岁,最大年龄76岁,平均年龄60.8岁,年龄中位数57岁。病例均有活禽农贸市场暴露史。病例报告县农贸市场外环境标本阳性率较未报告病例县农贸市场高,差异有统计学意义(χ2 = 6.73,P＜0.05)。结论 阿坝州此次疫情地区分散,时间集中,农贸市场禽类暴露是感染的危险因素。采取关闭活禽市场能明显控制疫情发展;病例以散发为主,目前暂无足够的证据支持病毒在人与人之间传播。     

我国H7N9禽流感病毒血凝素和神经氨酸酶基因的分子进化分析

  目的  通过对安徽省安庆市人感染H7N9禽流感外环境标本检测,分析外环境中病毒污染情况,研究判断人感染H7N9的风险,为制定防控措施提供依据。  方法  于2017年1月5日 — 2月22日,采用完全随机抽样的方法,采集安庆市38家农贸市场、4例确诊人感染H7N9禽流感病例居家禽类相关标本共324份,用实时荧光定量RT-PCR方法进行甲型流感病毒通用核酸检测,对阳性标本进一步进行H7N9检测。  结果  安庆市H7N9禽流感病毒阳性率28.40 %,11个县（市、区）中有10个检出H7N9病毒阳性,阳性率90.90 % （10/11）。主城区阳性率37.68 %（26/69）高于非主城区,差异有统计学意义（χ² = 9.23,P < 0.05）;鸡、鸭、鸽子标本中,鸡标本阳性率最高31.75 %（80/252）,差异有统计学意义（χ² = 6.57,P < 0.05）;农贸市场来源的标本阳性率为29.77 %（92/309）,病例家来源的标本阳性率为0,差异有统计学意义（χ² = 6.24,P < 0.05）;不同类型标本中,咽拭子和肛拭子阳性率最高,分别为42.86 %（9/21）和40.00 %（2/5）,其次为饮水和污水;发生人感染病例前外环境标本阳性率38.71 %（12/31）高于发生后,但2者间的差异无统计学意义（χ² = 1.79,P > 0.05）。  结论  安庆市农贸市场存在H7N9禽流感病毒污染。     

Protective immunity to H7N9 influenza viruses elicited by synthetic DNA vaccine

Despite an intensive vaccine program influenza infections remain a major health problem, due to the viruses’ ability to change its envelope glycoprotein hemagglutinin (HA), through shift and drift, permitting influenza to escape protection induced by current vaccines or natural immunity. Recently a new variant, H7N9, has emerged in China causing global concern. First, there have been more than 130 laboratory-confirmed human infections resulting in an alarmingly high death rate (32.3%). Second, genetic changes found in H7N9 appear to be associated with enabling avian influenza viruses to spread more effectively in mammals, thus transmitting infections on a larger scale. Currently, no vaccines or drugs are effectively able to target H7N9. Here, we report the rapid development of a synthetic consensus DNA vaccine (pH7HA) to elicit potent protective immunity against the H7N9 viruses. We show that pH7HA induces broad antibody responses that bind to divergent HAs from multiple new members of the H7N9 family. These antibody responses result in high-titer HAI against H7N9. Simultaneously, this vaccine induces potent polyfunctional effector CD4 and CD8T cell memory responses. Animals vaccinated with pH7HA are completely protected from H7N9 virus infection and any morbidity associated with lethal challenge. This study establishes that this synthetic consensus DNA vaccine represents a new tool for targeting emerging infection, and more importantly, its design, testing and development into seed stock for vaccine production in a few days in the pandemic setting has significant implications for the rapid deployment of vaccines protecting against emerging infectious diseases.     

H7N9 influenza and its impact on pregnancy

This short article specifically focuses on the new emerging H7N9 influenza which has just been observed since early 2013. As a new disease, it is lack for the knowledge on the new H7N9 influenza. Here, the author will discuss on the impact of emerging H7N9 influenza on pregnancy.     

广西南宁市一起家庭聚集性人感染H7N9禽流感疫情的调查

目的 探讨南宁市一起人感染H7N9禽流感的传播模式。方法 应用现场流行病学方法调查2例病例及其82名密切接触者, 对采集的相关标本进行H7N9禽流感病毒核酸检测和病毒分离, 并分析基因序列和进化树同源性。结果 病例A在最后一次暴露于广东中山市活禽市场后4 d于当地发病, 并在发病后第2天返回广西南宁市横县家中。病例B(病例A之子, 5岁)无明确禽类接触史, 但与病例A同居一室密切接触, 4 d后发病。从2例中均分离出H7N9禽流感病毒, 2株病毒基因序列和系统进化树分析具有高度同源性, 且关系最近。指示病例(病例A)的其他81名密切接触者未出现人感染H7N9禽流感病毒症状。结论 二代病例(病例B)可能在无防护情况下密切接触指示病例而感染, 提示H7N9禽流感病毒可通过人-人传播, 但其传染力有限且非持续性。     

Detecting Spread of Avian Influenza A(H7N9) Virus Beyond China

During February 2013–March 2015, a total of 602 human cases of low pathogenic avian influenza A(H7N9) were reported; no autochthonous cases were reported outside mainland China. In contrast, since highly pathogenic avian influenza A(H5N1) reemerged during 2003 in China, 784 human cases in 16 countries and poultry outbreaks in 53 countries have been reported. Whether the absence of reported A(H7N9) outside mainland China represents lack of spread or lack of detection remains unclear. We compared epidemiologic and virologic features of A(H5N1) and A(H7N9) and used human and animal influenza surveillance data collected during April 2013–May 2014 from 4 Southeast Asia countries to assess the likelihood that A(H7N9) would have gone undetected during 2014. Surveillance in Vietnam and Cambodia detected human A(H5N1) cases; no A(H7N9) cases were detected in humans or poultry in Southeast Asia. Although we cannot rule out the possible spread of A(H7N9), substantial spread causing severe disease in humans is unlikely.     

Squalene-adjuvanted H7N9 virus vaccine induces robust humoral immune response against H7N9 and H7N7 viruses

Recent cases of avian influenza H7N9 have caused great concerns that virus may become transmittable between humans. It is imperative to develop an effective vaccine to fight against the pandemic potential of this H7N9 influenza virus to protect human from the disease. This study aims to investigate an optimized formulation for the development of H7N9 vaccines. Various doses of H7N9 inactivated whole or split-virus antigens (0.5, 1.5, or 3 μg based on hemagglutinin content) combined with squalene-based adjuvant (AddaVAX), aluminum hydroxide Al(OH)₃ or without adjuvant were evaluated for the efficacy of H7N9 vaccine regiments in mice. With either H7N9 whole or split-virus based vaccines, AddaVAX-adjuvanted formulations were the most immunogenic in eliciting significant humoral immune response against H7N9 virus and exhibited strong cross-reactive response in hemagglutination inhibition (HAI) and viral-neutralization assays against H7N7 virus as well. In contrast, formulations with Al(OH)₃ or without adjuvant were less immunogenic and elicited lower titers of HAI and microneutralization assays against both viruses. Dose-sparing experiments suggested that the formulation with as low as 0.004 μg of split or whole virus vaccine antigens together with 50% AddaVAX provided sufficient sero-protective HAI titers and achieved essential virus-neutralizing antibody titers against H7-subtype influenza viruses in mice. Protection experiments demonstrated that the formulation of 0.004 μg to 0.5 μg of split-virion vaccines with AddaVAX conferred full protection against viral challenge up to 100 LD50 of wild-type H7N9 virus, with 0% survival in placebo group. Taken together, our study demonstrates that squalene-based adjuvant can significantly enhance the protective efficacy of H7N9 virus vaccine and provides a useful strategy to confront the potential pandemic outbreaks of H7N9 virus.     

A single dose of whole inactivated H7N9 influenza vaccine confers protection from severe disease but not infection in ferrets

The H7N9 influenza virus caused significant mortality and morbidity in infected humans during an outbreak in China in 2013 stimulating vaccine development efforts. As previous H7-based vaccines have been poorly immunogenic in humans we sought to determine the immunogenic and protective properties of an inactivated whole virus vaccine derived from a 2013 H7N9 virus in ferrets. As whole virus vaccine preparations have been shown to be more immunogenic in humans, but less likely to be used, than split or surface antigen formulations, we vaccinated ferrets with a single dose of 15, 30, or 50 μg of the vaccine and subsequently challenged with wild-type A/Anhui/1/2013 (H7N9) either by direct instillation or by contact with infected animals. Although ferrets vaccinated with higher doses of vaccine had higher serum hemagglutinin inhibition (HI) titers, the titers were still low. During subsequent instillation challenge, however, ferrets vaccinated with 50 μg of vaccine showed no illness and shed significantly less virus than mock vaccinated controls. All vaccinated ferrets had lower virus loads in their lungs as compared to controls. In a separate study where unvaccinated-infected ferrets were placed in the same cage with vaccinated-uninfected ferrets, vaccination did not prevent infection in the contact ferrets, although they showed a trend of lower viral load. Overall, we conclude that inactivated whole-virus H7N9 vaccine was able to reduce the severity of infection and viral load, despite the lack of hemagglutinin-inhibiting antibodies.     

One-shot vaccination with an insect cell-derived low-dose influenza A H7 virus-like particle preparation protects mice against H7N9 challenge

Human infections with a novel influenza A H7N9 subtype virus were reported in China recently. The virus caused severe disease with high mortality rates and it raised concerns over its pandemic potential. Here, we assessed in the mouse model protective efficacy of single immunisations with low vaccine doses of insect cell-derived H7 virus-like particles, consisting of hemagglutinin and matrix protein. Vaccinated mice were fully protected and survived a stringent lethal challenge (100 mLD50) with H7N9, even after a single, unadjuvanted, low vaccine dose (0.03 μg). Serum analysis revealed broad reactivity and hemagglutination inhibition activity across a panel of divergent H7 strains. Moreover, we detected significant levels of cross-reactivity to related group 2 hemagglutinins. These data demonstrate that virus-like particle vaccines have the potential to induce broadly protective immunity against the novel H7N9 virus and a variety of other H7 strains.     

2009年北京市学生甲型H1N1流感流行特征

目的描述北京市学生甲型H1N1流感感染情况,分析其流行各阶段的特征。方法收集2009年5月11日～12月31日中国疾病预防控制中心(CDC)《疾病监测信息系统》中报告的学生甲型H1N1流感确诊病例个案信息,应用Excel和SPSS统计软件进行分析。结果 2009年5月11日～12月31日,北京市共确诊甲型H1N1流感学生病例6568例,平均年龄(13.7±4.0)岁,小学和初中学生最多,占68.87%。甲型H1N1在学生中的传播过程分为4个时期。5～6月以外籍输入性病例为主,7～8月聚集性疫情由中小学生向大学生扩散,9～10月,日均确诊病例数突增至94.58人/d,城区发病人数是郊区的2.04倍,44.40%的确诊病例为学校聚集性病例,11～12月,日均确诊病例数迅速下降至3.06人/d,进入12月以后维持在较低水平。结论北京市学生甲型H1N1流感流行特征为:低年龄组高发,从低年龄组向高年龄组扩散,城区向郊区扩散和学校聚集性的特点。     

Complex reassortment of polymerase genes in Asian influenza A virus H7 and H9 subtypes

The epidemic first caused by a novel H7N9 avian influenza A virus (IAV) has emerged in China recently. Meanwhile, a novel H7N7 IAV with the ability to infect mammals was also found in China. Both IAVs of H7 subtype possess internal genes originating from H9N2. As internal polymerase genes play a key role for interspecies transmission of IAVs, it is important to trace the reassortment history of polymerase genes in the IAVs of H7 and H9 subtypes. Here, by comprehensive phylogenetic analyses of Asian H7 and H9 polymerases, we showed a significant incongruence among the tree topologies of polymerase genes PA, PB1 and PB2, which suggested frequent intra-subtype reassortments in the IAVs of H9N2. Moreover, the PA gene of H1N1pdm09 clustered with that of H9N2 located at the basal position of clade A, including most strains isolated from mammals and the recent novel H7N9 in the phylogenetic tree of PA. This finding indicated that the H1N1pdm09-like PA gene may play an important role in the human H7N9 epidemic. Results also showed that the earlier strains of H7 subtype were divided into several clusters dispersed within the strains of H9N2, implying multiple direct and/or indirect reassortments may occur between H7 and H9 polymerase genes. Furthermore, the most recent reassortments occurred multiply on the polymerase genes of the newly emerging H7N9 isolated from human in South China, evolving E627K mutation in PB2 independently. These results suggest that the reassortment history of polymerase genes in Asian IAVs of H7 and H9 subtypes is complex and timely evolutionary analyses on the novel H7N9 with newly adapted polymerase are necessary for preventing a potential outbreak in South China.