Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

Gao, Rongbao; Cao, Bin; Hu, Yunwen; Feng, Zijian; Wang, Dayan; Hu, Wanfu; Chen, Jian; Zhang, Jie; Qiu, Haibo; Xu, Ke; Xu, Xuewei; Lu, Hongzhou; Zhu, Wenfei; Gao, Zhancheng; Xiang, Nijuan; Shen, Yinzhong; He, Zhike; Gu, Yong; Zhang, Zhiyong; Yang, Yi; Zhao, Xiang; Zhou, Lei; Li, Xiaodan; Zou, Shumei; Zhang, Ye; Li, Xiyan; Yang, Lei; Guo, Jianhua; Dong, Jie; Li, Qun; Dong, Libo; Zhu, Yun; Bai, Tian; Wang, Shiwen; Hao, Pei; Yang, Weizhong; Zhang, Yanping; Han, Jun; Yu, Hongjie; Li, Dexin; Gao, George F.; Wu, Guizhen; Wang, Yu; Yuan, Zhenghong; Shu, Yuelong

doi:10.1056/nejmoa1304459

Cited by 2,131 publications

(2,092 citation statements)

References 24 publications

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“…The first human infections with influenza A(H7N9) virus were identified in China in March 20131. As of July 19, 2016, there were 793 influenza A(H7N9) virus infections in humans reported globally, including 319 fatalities.…”

Section: Introductionmentioning

confidence: 99%

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

Xiang

Bai

Kang

et al. 2017

Influenza Resp Viruses

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BackgroundThe first human infections of novel avian influenza A(H7N9) virus were identified in China in March 2013. Sentinel surveillance systems and contact tracing may not identify mild and asymptomatic human infections of influenza A(H7N9) virus.ObjectivesWe assessed the seroprevalence of antibodies to influenza A(H7N9) virus in three populations during the early stages of the epidemic.Patients/MethodsFrom March 2013 to May 2014, we collected sera from the general population, poultry workers, and contacts of confirmed infections in nine Chinese provinces reporting human A(H7N9) infections and, for contacts, second sera 2‐3 weeks later. We screened for A(H7N9) antibodies by advanced hemagglutination inhibition (HI) assay and tested sera with HI titers ≥20 by modified microneutralization (MN) assay. MN titers ≥20 or fourfold increases in paired sera were considered seropositive.ResultsAmong general population sera (n=1480), none were seropositive. Among poultry worker sera (n=1866), 28 had HI titers ≥20; two (0.11%, 95% CI: 0.02‐0.44) were positive by MN. Among 61 healthcare and 117 non‐healthcare contacts’ sera, five had HI titers ≥20, and all were negative by MN. There was no seroconversion among 131 paired sera.ConclusionsThere was no evidence of widespread transmission of influenza A(H7N9) virus during March 2013 to May 2014, although A(H7N9) may have caused rare, previously unrecognized infections among poultry workers. Although the findings suggest that there were few undetected cases of influenza A(H7N9) early in the epidemic, it is important to continue monitoring transmission as virus and epidemic evolve.

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Section: Introductionmentioning

confidence: 99%

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

Xiang

Bai

Kang

et al. 2017

Influenza Resp Viruses

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“…1,2 Since then, China has experienced five epidemics of human infection with H7N9. 3,4 Outbreaks typically occur in a seasonal pattern peaking during January-March and dropping off by end of May.…”

Section: Concern For An Avian H7n9 Influenza Pandemicmentioning

confidence: 99%

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

Moise

Biron

Boyle

et al. 2018

Human Vaccines & Immunotherapeutics

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The delayed availability of vaccine during the 2009 H1N1 influenza pandemic created a sense of urgency to better prepare for the next influenza pandemic. Advancements in manufacturing technology, speed and capacity have been achieved but vaccine effectiveness remains a significant challenge. Here, we describe a novel vaccine design strategy called immune engineering in the context of H7N9 influenza vaccine development. The approach combines immunoinformatic and structure modeling methods to promote protective antibody responses against H7N9 hemagglutinin (HA) by engineering whole antigens to carry seasonal influenza HA memory CD4+ T cell epitopes – without perturbing native antigen structure – by galvanizing HA-specific memory helper T cells that support sustained antibody development against the native target HA. The premise for this vaccine concept rests on (i) the significance of CD4+ T cell memory to influenza immunity, (ii) the essential role CD4+ T cells play in development of neutralizing antibodies, (iii) linked specificity of HA-derived CD4+ T cell epitopes to antibody responses, (iv) the structural plasticity of HA and (v) an illustration of improved antibody response to a prototype engineered recombinant H7-HA vaccine. Immune engineering can be applied to development of vaccines against pandemic concerns, including avian influenza, as well as other difficult targets.

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“…The goal of this study was to continue evaluation of mAb‐based alternative methods for measuring the potency of inactivated influenza vaccines, focusing on A(H7N9) pandemic influenza vaccines produced following the emergence of novel A(H7N9) viruses in China in 2013 that resulted in hundreds of human fatalities 14, 15. Several mAbs, recognizing different epitopes on the H7 HA, were identified, characterized, and evaluated in both a mAb‐capture ELISA and a mAb‐based biolayer interferometry (BLI) assay.…”

Section: Introductionmentioning

confidence: 99%

Potency determination of inactivated H7 influenza vaccines using monoclonal antibody‐based ELISA and biolayer interferometry assays

Vasudevan

Woerner

Schmeisser

et al. 2017

Influenza Resp Viruses

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BackgroundThe single radial immunodiffusion (SRID) assay, the accepted method for determining potency of inactivated influenza vaccines, measures an immunogenic form of the influenza hemagglutinin. Nevertheless, alternative methods for measuring vaccine potency have been explored to address some of the weaknesses of the SRID assay, including limited sensitivity and the requirement for large amounts of standardized reagents. Monoclonal antibody (mAb)‐based potency assays also have the ability to detect and measure relevant immunogenic forms of HA.ObjectivesThe objective of this study was to continue evaluation of mAb‐based alternative methods for measuring the potency of inactivated influenza vaccines, focusing on A(H7N9) pandemic influenza vaccines.MethodsSeveral murine mAbs that recognize different epitopes on the H7 hemagglutinin (HA) were identified and characterized. These mAbs were evaluated in both a mAb‐capture ELISA and a mAb‐based biolayer interferometry (BLI) assay.ResultsResults indicated that potency of inactivated A(H7N9) vaccines, including vaccine samples that were stressed by heat treatment, measured by either alternative method correlated well with potency determined by the traditional SRID potency assay.ConclusionsThe availability of multiple H7 mAbs, directed to different HA epitopes, provides needed redundancy in the potency analysis as A(H7N9) viruses continue to evolve antigenically and suggests the importance of having a broad, well‐characterized panel of mAbs available for development of vaccines against influenza strains with pandemic potential. In addition, the results highlight the potential of mAb‐based platform such as ELISA and BLI for development as alternative methods for determining the potency of inactivated influenza vaccines.

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Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

Abstract: Novel reassortant H7N9 viruses were associated with severe and fatal respiratory disease in three patients. (Funded by the National Basic Research Program of China and others.).

Cited by 2,131 publications

References 24 publications

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

Sero‐epidemiologic study of influenza A(H7N9) infection among exposed populations, China 2013‐2014

T cell epitope engineering: an avian H7N9 influenza vaccine strategy for pandemic preparedness and response

Potency determination of inactivated H7 influenza vaccines using monoclonal antibody‐based ELISA and biolayer interferometry assays

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