Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection

Gao, Hainv; Lu, Hongzhou; Cao, Bin; Du, Bin; Shang, Hong; Gan, Jing; Lu, Shuaiyao; Yang, Yida; Fang, Qiang; Shen, Yinzhong; Xi, Xiuming; Gu, Qin; Zhou, Xianmei; Qu, Hongping; Zheng, Yan; Li, Fangming; Zhao, Wei; Gao, Zhancheng; Wang, Guangfa; Ruan, Lifang; Wang, Weihong; Ye, Jun; Cao, Haipeng; Li, Xingwang; Zhang, Wenhong; Fang, Xu-Chen; He, Jian; Liang, Weifeng; Xie, Jian‐Wei; Zeng, Mei; Wu, Xin; Li, Jun; Xia, Qi; Jin, Zhaochen; Chen, Qi; Tang, Chao; Zhang, Zhiyong; Hou, Bao-Min; Feng, Zhixian; Sheng, Jifang; Zhong, Nanshan; Li, Lanjuan

doi:10.1056/nejmoa1305584

Cited by 612 publications

(620 citation statements)

References 16 publications

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“…The high mortality associated with H7N9 infection and development of ARDS is similar to what has been reported for H5N1. An associated cytokine storm has been described in both of these patient groups, with proinflammatory cytokines/chemokines documented in plasma and pulmonary lavage samples (1)(2)(3). The increased cytokine responses have recently been correlated with increased severity and mortality observed in patients (2)(3)(4).…”

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confidence: 96%

“…An associated cytokine storm has been described in both of these patient groups, with proinflammatory cytokines/chemokines documented in plasma and pulmonary lavage samples (1)(2)(3). The increased cytokine responses have recently been correlated with increased severity and mortality observed in patients (2)(3)(4). Elevated levels of interleukin (IL)-10, IL-6, IL-8, and macrophage inflammatory protein-1β (MIP-1β) in plasma were found to be predictive of a less favorable or fatal outcome.…”

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confidence: 99%

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A broadly neutralizing human monoclonal antibody is effective against H7N9

Tharakaraman

Subramanian

Viswanathan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Emerging strains of influenza represent a significant public health threat with potential pandemic consequences. Of particular concern are the recently emerged H7N9 strains which cause pneumonia with acute respiratory distress syndrome. Estimates are that nearly 80% of hospitalized patients with H7N9 have received intensive care unit support. VIS410, a human antibody, targets a unique conserved epitope on influenza A. We evaluated the efficacy of VIS410 for neutralization of group 2 influenza strains, including H3N2 and H7N9 strains in vitro and in vivo. VIS410, administered at 50 mg/kg, protected DBA mice infected with A/Anhui/2013 (H7N9), resulting in significant survival benefit upon single-dose (−24 h) or double-dose (−12 h, +48 h) administration (P < 0.001). A single dose of VIS410 at 50 mg/kg (−12 h) combined with oseltamivir at 50 mg/kg (−12 h, twice daily for 7 d) in C57BL/6 mice infected with A/Shanghai 2/2013 (H7N9) resulted in significant decreased lung viral load (P = 0.002) and decreased lung cytokine responses for nine of the 11 cytokines measured. Based on these results, we find that VIS410 may be effective either as monotherapy or combined with antivirals in treating H7N9 disease, as well as disease from other influenza strains.

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confidence: 96%

mentioning

confidence: 99%

A broadly neutralizing human monoclonal antibody is effective against H7N9

Tharakaraman

Subramanian

Viswanathan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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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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“…While mainland China was the source of nearly all of these cases (552 cases plus several exported cases), several cases were confirmed in Hong Kong (12 cases), Taipei (four cases), Malaysia (one case) and Canada (two cases from China) (WHO, 2015). Most H7N9 patients have a high fever and cough at the onset of the illness, and rapidly develop lower respiratory tract infections, which cause severe symptoms (Gao et al, 2013a;Shen et al, 2014). H7N9 infection causes pneumonia and acute respiratory distress syndrome (ARDS), which result in a case fatality rate of more than 30 % (Chi et al, 2013;Wang et al, 2014;Yu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory cytokine dysregulation is associated with novel avian influenza A (H7N9) virus in primary human macrophages

Zhao

Ding

et al. 2016

Journal of General Virology

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Since March 2013, more than 500 laboratory-confirmed human H7N9 influenza A virus infection cases have been recorded, with a case fatality rate of more than 30 %. Clinical research has shown that cytokine and chemokine dysregulation contributes to the pathogenicity of the H7N9 virus. Here, we investigated cytokine profiles in primary human macrophages infected with the novel H7N9 virus, using cytokine antibody arrays. The levels of several pro-inflammatory cytokines, particularly TNF-a, were increased in H7N9-infected macrophages. Induction of the transcriptional and translational levels of the pro-inflammatory cytokines by H7N9 virus seemed to be intermediate between those induced by highly pathogenic avian H5N1 and pandemic human H1N1 viruses, which were detected by ELISA and real-time quantitative PCR, respectively. Additionally, compared with H5N1, the upregulation of pro-inflammatory cytokines caused by H7N9 infection occurred rapidly but mildly. Our results identified the overall profiles of cytokine and chemokine induction by the H7N9 influenza virus in an in vitro cell-culture model, and could provide potential therapeutic targets for the control of severe human H7N9 disease.

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Clinical Findings in 111 Cases of Influenza A (H7N9) Virus Infection

Abstract: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Cited by 612 publications

References 16 publications

A broadly neutralizing human monoclonal antibody is effective against H7N9

A broadly neutralizing human monoclonal antibody is effective against H7N9

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

Pro-inflammatory cytokine dysregulation is associated with novel avian influenza A (H7N9) virus in primary human macrophages

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