Population-level antibody estimates to novel influenza A/H7N9.
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ABSTRACT:
SUBMITTER: Boni MF
PROVIDER: S-EPMC3719906 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Since its first emergence in East China in early 2013, many cases of avian influenza A H7N9 have been reported. The disease has extended to 22 provinces in mainland China and some surrounding areas. Strategies to combat viral infection are urgently needed. We previously isolated a human monoclonal antibody, HNIgGA6, that neutralized the H7N9 virus both in vitro and in vivo In this study, we determined the crystal structure of viral hemagglutinin (HA) globular head bound to the fragment antigen-binding region (Fab) of HNIgGA6. The crystal structure shows that the tip of the HNIgGA6 heavy-chain complementarity-determining region 3 (HCDR3) directly interposes into the receptor binding site (RBS) and mimics, in many respects, the interaction of the sialic acid receptor. Three residues at Y98, H183, and E190, which are critical to human cellular receptor binding, are also essential for HNIgGA6 recognition. Meanwhile, dual mutations at V186G and L226Q in RBS were able to disrupt viral HA1 binding with the antibody. Our study provides a better understanding of the mechanism for protective antibody recognition and a sound foundation for the design of therapeutic drugs and vaccines against H7N9 influenza.IMPORTANCE Neutralization by antibody is one of the most important mechanisms for a host to defend against viral infections. Human-originated antibody HNIgGA6 was generated in response to the natural infectious H7N9 virus and showed potential for use in suppression of H7N9 infection, with possible therapeutic implications. The crystal structure of the HNIgGA6/HA1 complex provided new insight into the protective immune response to H7N9 virus in humans, as well as possibilities for the development of effective H7N9 pandemic vaccines and antiviral molecules.
| S-EPMC5809732 | biostudies-literature
Project description:UnlabelledA novel avian-origin influenza A/H7N9 virus infecting humans was first identified in March 2013 and, as of 30 May 2013, has caused 132 human infections leading to 33 deaths. Phylogenetic studies suggest that this virus is a reassortant, with the surface hemagglutinin (HA) and neuraminidase (NA) genes being derived from duck and wild-bird viruses, respectively, while the six "internal gene segments" were derived from poultry H9N2 viruses. Here we determine the pathogenicity of a human A/Shanghai/2/2013 (Sh2/H7N9) virus in healthy adult mice in comparison with that of A/chicken/Hong Kong/HH8/2010 (ck/H9N2) virus, highly pathogenic avian influenza (HPAI) A/Hong Kong/483/1997 (483/H5N1) virus, and a duck influenza A H7N9 virus of different genetic derivation, A/duck/Jiangxi/3286/2009 (dk/H7N9). Intranasal infection of mice with Sh2/H7N9 virus doses of 10(3), 10(4), and 10(5) PFU led to significant weight loss without fatality. This virus was more pathogenic than dk/H7N9 and ck/H9N2 virus, which has six internal gene segments that are genetically similar to Sh2/H7N9. Sh2/H7N9 replicated well in the nasal cavity and lung, but there was no evidence of virus dissemination beyond the respiratory tract. Mice infected with Sh2/H7N9 produced higher levels of proinflammatory cytokines in the lung and serum than did ck/H9N2 and dk/H7N9 but lower levels than 483/H5N1. Cytokine induction was positively correlated with virus load in the lung at early stages of infection. Our results suggest that Sh2/H7N9 virus is able to replicate and cause disease in mice without prior adaptation but is less pathogenic than 483/H5N1 virus.ImportanceAn H7N9 virus isolate causing fatal human disease was found to be more pathogenic for mice than other avian H9N2 or H7N9 viruses but less pathogenic than the highly pathogenic avian influenza virus (HPAI) H5N1. Similarly, the ability of Sh2/H7N9 to elicit proinflammatory cytokines in the lung and serum of mice was intermediate to ck/H9N2 and dk/H7N9 on the one hand and HPAI H5N1 on the other. These findings accord with the observed epidemiology in humans, in whom, as with seasonal influenza viruses, H7N9 viruses cause severe disease predominantly in older persons while HPAI H5N1 can cause severe respiratory disease and death in children and young adults.
| S-EPMC3705449 | biostudies-literature
Project description:The emergence of the novel H7N9 influenza A virus (IAV) has caused global concerns about the ability of this virus to spread between humans. Analysis of the receptor-binding properties of this virus using a recombinant protein approach in combination with fetuin-binding, glycan array and human tissue-binding assays demonstrates increased binding of H7 to both α2-6 and α2-8 sialosides as well as reduced binding to α2-3-linked SIAs compared to a closely related avian H7N9 virus from 2008. These differences could be attributed to substitutions Q226L and G186V. Analysis of the enzymatic activity of the neuraminidase N9 protein indicated a reduced sialidase activity, consistent with the reduced binding of H7 to α2-3 sialosides. However, the novel H7N9 virus still preferred binding to α2-3- over α2-6-linked SIAs and was not able to efficiently bind to epithelial cells of human trachea in contrast to seasonal IAV, consistent with its limited human-to-human transmission.
| S-EPMC3808826 | biostudies-literature
Project description:Conventional inactivated avian influenza vaccines have performed poorly in past vaccine trials, leading to the hypothesis that they are less immunogenic than seasonal influenza vaccines. We tested this hypothesis by comparing the immunogenicity of the H5N1 and H7N9 vaccines (avian influenza vaccines) to a seasonal trivalent inactivated influenza vaccine in naïve ferrets, administered with or without the adjuvants MF59 or AS03. Vaccine immunogenicity was assessed by measuring neutralizing antibody titers against hemagglutinin and neuraminidase and by hemagglutinin -specific IgG levels. Two doses of unadjuvanted vaccines induced low or no HA-specific IgG responses and hemagglutination-inhibiting titers. Adjuvanted vaccines induced comparable IgG-titers, but poorer neutralizing antibody titers for the H5 vaccine. All adjuvanted vaccines elicited detectable anti- neuraminidase -antibodies with the exception of the H5N1 vaccine, likely due to the low amounts of neuraminidase in the vaccine. Overall, the H5N1 vaccine had poorer capacity to induce neutralizing antibodies, but not HA-specific IgG, compared to H7N9 or trivalent inactivated influenza vaccine.
| S-EPMC5627238 | biostudies-literature
Project description:Avian influenza A(H7N9) virus has caused 5 epidemic waves in China since its emergence in 2013. We investigated the dynamic changes of antibody response to this virus over 1 year postinfection in 25 patients in Suzhou City, Jiangsu Province, China, who had laboratory-confirmed infections during the fifth epidemic wave, October 1, 2016-February 14, 2017. Most survivors had relatively robust antibody responses that decreased but remained detectable at 1 year. Antibody response was variable; several survivors had low or undetectable antibody titers. Hemagglutination inhibition titer was >1:40 for <40% of the survivors. Measured in vitro in infected mice, hemagglutination inhibition titer predicted serum protective ability. Our findings provide a helpful serologic guideline for identifying subclinical infections and for developing effective vaccines and therapeutics to counter H7N9 virus infections.
| S-EPMC5875250 | biostudies-literature
Project description:BackgroundThe new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.MethodsH7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.ResultsThe mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.ConclusionThe mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
| S-EPMC9276153 | biostudies-literature
Project description:Emerging H7N9 influenza virus infections in Asia have once more spurred the development of effective prepandemic H7 vaccines. However, many vaccines based on avian influenza viruses--including H7--are poorly immunogenic, as measured by traditional correlates of protection. Here we reevaluated sera from an H7N1 human vaccine trial performed in 2006. We examined cross-reactive antibody responses to divergent H7 strains, including H7N9, dissected the antibody response into head- and stalk-reactive antibodies, and tested the in vivo potency of these human sera in a passive-transfer H7N9 challenge experiment with mice. Although only a low percentage of vaccinees induced neutralizing antibody responses against the homologous vaccine strain and also H7N9, we detected strong cross-reactivity to divergent H7 hemagglutinins (HAs) in a large proportion of the cohort with a quantitative enzyme-linked immunosorbent assay. Furthermore, H7N1 vaccination induced antibodies to both the head and stalk domains of the HA, which is in sharp contrast to seasonal inactivated vaccines. Finally, we were able to show that both neutralizing and nonneutralizing antibodies improved in vivo virus clearance in a passive-transfer H7N9 challenge mouse model.
| S-EPMC4135918 | biostudies-literature
Project description:BackgroundNational estimates of influenza burden may not reflect state-level influenza activity, and local surveillance may not capture the full burden of influenza.MethodsTo provide state-level information about influenza burden, we estimated excess pneumonia and influenza (P&I) and respiratory and circulatory (R&C) hospitalizations and deaths in Colorado from local hospital discharge records, death certificates, and influenza virus surveillance using negative binomial models.ResultsFrom July 2007 to June 2016, influenza was associated with an excess of 17 911 P&I hospitalizations (95%CI: 15 227, 20 354), 30 811 R&C hospitalizations (95%CI: 24 344, 37 176), 1,064 P&I deaths (95%CI: 757, 1298), and 3828 R&C deaths (95%CI: 2060, 5433). There was a large burden of influenza A(H1N1) among persons aged 0-64 years, with high median seasonal rates of excess hospitalization among persons aged 0-4 years. Persons aged ≥65 years experienced the largest numbers and highest median seasonal rates of excess hospitalization and death associated with influenza A (H3N2). The burden of influenza B was generally lower, with elevated median seasonal rates of excess hospitalization among persons aged 0-4 years and ≥65 years.ConclusionsThese findings complement existing influenza surveillance. Periodic state-level estimates of influenza disease burden may be useful for setting state public health priorities and planning prevention and control initiatives.
| S-EPMC7040963 | biostudies-literature
Project description:In spring 2013, influenza A(H7N9) virus was isolated from an apparently healthy tree sparrow in Chongming Dongping National Forest Park, Shanghai City, China. The entire gene constellation of the virus is similar to that of isolates from humans, highlighting the need to monitor influenza A(H7N9) viruses in different species.
| S-EPMC4012817 | biostudies-literature
Project description:BackgroundIn late March 2013, a new avian-origin influenza virus emerged in eastern China. This H7N9 subtype virus has since infected 240 people and killed 60, and has awakened global concern as a potential pandemic threat. Ecological niche modeling has seen increasing applications as a useful tool in mapping geographic potential and risk of disease transmission.Methodology/principalsWe developed two datasets based on seasonal variation in Normalized Difference Vegetation Index (NDVI) from the MODIS sensor to characterize environmental dimensions of H7N9 virus. One-third of well-documented cases was used to test robustness of models calibrated based on the remaining two-thirds, and model significance was tested using partial ROC approaches. A final niche model was calibrated using all records available.Conclusions/significanceCentral-eastern China appears to represent an area of high risk for H7N9 spread, but suitable areas were distributed more spottily in the north and only along the coast in the south; highly suitable areas also were identified in western Taiwan. Areas identified as presenting high risk for H7N9 spread tend to present consistent NDVI values through the year, whereas unsuitable areas show greater seasonal variation.
| S-EPMC3972139 | biostudies-literature