Development and applications of universal H7 subtype-specific antibodies for the analysis of influenza H7N9 vaccines

Gravel, Caroline; Elmgren, C.; Muralidharan, Abenaya; Hashem, Anwar M.; Jaentschke, Bozena; Xu, Kangwei; Widdison, J; Arnold, K S; Farnsworth, Aaron; Rinfret, Aline; Domselaar, Gary Van; Wang, Junzhi; Li, Changgui; Li, Xuguang

doi:10.1016/j.vaccine.2015.01.034

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…Likewise, mAb # 3 specifically bound to two different lineages of IBV with equal efficiency, without any cross‐reactivity to IAV (Figure 6c,d). The availability of group‐specific mAbs will be instrumental in establishing a novel ELISA‐based approach for the quantitation of trivalent seasonal influenza vaccines (Chae, Kim, Kim, et al, 2019; Gravel et al, 2015; Rajendran et al, 2018), pre‐pandemic vaccines, or HA stalk‐based cross‐protective universal vaccine (Erbelding et al, 2018; Jang & Seong, 2014). MAbs that bind to HA‐stalk have been reported to potentiate ADCC (Jegaskanda, Reading, & Kent, 2014).…”

Section: Resultsmentioning

confidence: 99%

Built‐in RNA‐mediated chaperone (chaperna) for antigen folding tailored to immunized hosts

Kim

Lim

Sung

et al. 2020

Biotech & Bioengineering

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High-quality antibody (Ab) production depends on the availability of immunologically relevant antigens. We present a potentially universal platform for generating soluble antigens from bacterial hosts, tailored to immunized animals for Ab production. A novel RNA-dependent chaperone, in which the target antigen is genetically fused with an RNA-interacting domain (RID) docking tag derived from the immunized host, promotes the solubility and robust folding of the target antigen. We selected the N-terminal tRNA-binding domain of lysyl-tRNA synthetase (LysRS) as the RID for fusion with viral proteins and demonstrated the expression of the RID fusion proteins in their soluble and native conformations; immunization predominantly elicited Ab responses to the target antigen, whereas the "self" RID tag remained nonimmunogenic. Differential immunogenicity of the fusion proteins greatly enriched and simplified the screening of hybridoma clones of monoclonal antibodies (mAbs), enabling specific and sensitive serodiagnosis of MERS-CoV infection. Moreover, mAbs against the consensus influenza hemagglutinin stalk domain enabled a novel assay for trivalent seasonal influenza vaccines. The Fc-mediated effector function was demonstrated, which could be harnessed for the design of next-generation "universal" influenza vaccines. The nonimmunogenic built-in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics, and designer vaccines.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Section: Resultsmentioning

confidence: 99%

Built‐in RNA‐mediated chaperone (chaperna) for antigen folding tailored to immunized hosts

Kim

Lim

Sung

et al. 2020

Biotech & Bioengineering

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“…Following our analysis of the public database, a set of 15 amino acid consensus sequences were identified for each subtype in a procedure used to maximize conservation and surface accessibility as described previously 35 , 36 . Sequence QHPELTGLDCIRPCF (408–422) , designated as CNA1, was selected for N1, RTLLMNELGVPFHLG ( 159–173 ), designated as CNA2, for N2, and STFQKALLISPHRFG (90–104) , designated as CNAB, for NB (N2 numbering).…”

Section: Resultsmentioning

confidence: 99%

“…A multiple alignment was then performed for each subtype followed by extraction of the consensus sequences from full-gene genome, in which the conservation index were sorted by the degree of variation and determined by calculating the Shannon entropy for each position of amino acid 35 . Geneious 7.0.6 software was then used to confirm the bioinformatics findings and ensure the uniqueness in one subtype and universality of the selected peptide within its own subtype 36 .…”

Section: Methodsmentioning

confidence: 99%

Universal type/subtype-specific antibodies for quantitative analyses of neuraminidase in trivalent influenza vaccines

Gravel

et al. 2018

Sci Rep

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Both influenza viral hemagglutinin and neuraminidase can induce protective immune responses in humans. Although the viral hemagglutinin antigens have been quantified in influenza vaccines, the amounts of neuraminidase remain undetermined. Using comprehensive bioinformatics analyses of all neuraminidase sequences, we identified highly conserved and subtype-specific peptide epitopes within each of N1, N2 and type B neuraminidase groups. Mono-specific antibodies generated against these peptides bound to their respective subtype/type only while demonstrating remarkable specificity against the viral neuraminidase sequences without any cross-reactivity with allantoic and cellular proteins. Moreover, the subtype/type-specific antibodies were found not to interfere with one another when a mixture of vaccine samples was analysed. Importantly, immunoassay based on these antibodies can quantitatively determine neuraminidase in commercial trivalent vaccine samples. Analyses of vaccines from eight manufacturers using the same vaccine seeds revealed significant differences in neuraminidase levels. Specifically, while the ratio between neuraminidase and hemagglutinin in some products are found to be close 1/5, other products have a ratio of approximately 1/100, a level which is far below the theoretical ratio between neuraminidase and hemagglutinin in a virus. The antibody-based assays reported here could be of great value for better quality control of both monovalent and trivalent vaccines.

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“…Three ELISA-based H7 subtype- specific systems have been developed 27 – 29 . Recently, H7 subtype-specific Abs were reported to have vaccine efficacy 30 , 31 .…”

Section: Discussionmentioning

confidence: 99%

Improvement of a rapid diagnostic application of monoclonal antibodies against avian influenza H7 subtype virus using Europium nanoparticles

Yeo

Bao

Seo

et al. 2017

Sci Rep

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The development of a sensitive and rapid diagnostic test is needed for early detection of avian influenza (AI) H7 subtype. In this study, novel monoclonal antibodies (mAbs) against influenza A H7N9 recombinant hemagglutinin (rHA)1 were developed and applied to a Europium nanoparticle–based rapid fluorescent immunochromatographic strip test (FICT) to improve the sensitivity of the rapid diagnostic system. Two antibodies (2F4 and 6D7) exhibited H7 subtype specificity in a dot-FICT assay by optimization of the conjugate and the pH of the lysis buffer. The subtype specificity was confirmed by an immunofluorescence assay and Western blot analysis. The limit of detection of the FICT employing novel mAbs 31 ng/mL for H7N9 rHA1 and 40 hemagglutination units/mL for H7 subtype virus. Sensitivity was improved 25-fold using Europium as confirmed by comparison of colloidal gold-based rapid diagnostic kit using the 2F4 and 6D7 mAbs.

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Development and applications of universal H7 subtype-specific antibodies for the analysis of influenza H7N9 vaccines

Cited by 12 publications

References 31 publications

Built‐in RNA‐mediated chaperone (chaperna) for antigen folding tailored to immunized hosts

Built‐in RNA‐mediated chaperone (chaperna) for antigen folding tailored to immunized hosts

Universal type/subtype-specific antibodies for quantitative analyses of neuraminidase in trivalent influenza vaccines

Improvement of a rapid diagnostic application of monoclonal antibodies against avian influenza H7 subtype virus using Europium nanoparticles

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