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Search results for: Mouse Anti-Influenza-A HA H3N2 Antibodies

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#32274402   // To Up

Isolation of Neutralizing Human Single Chain Antibodies Against Conserved Hemagglutinin Epitopes of Influenza a Virus H3N2 Strain.

Immunotherapies using monoclonal antibodies against influenza A hemagglutinin (HA) has been an effective means for controlling Influenza spread. An alternative method for viral prophylaxis and treatment is the development of human single-chain variable fragment (scFv) antibodies with no human anti-mouse antibody (HAMA) response and high specificity. In the present study, two highly conserved sequences of HA were used to select specific neutralizing scFvs against H3N2 strain of influenza A virus.
Mahboubeh Poursiami, Setareh Moazen, Foroogh Nejatollahi, Afagh Moatari

1268 related Products with: Isolation of Neutralizing Human Single Chain Antibodies Against Conserved Hemagglutinin Epitopes of Influenza a Virus H3N2 Strain.

1 mL11 mL1mg1 mL1 ml200 0.5 mg1 mg100 2 100.00 ug

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#32098409   2020/02/22 To Up

Influenza Hemagglutinin Nanoparticle Vaccine Elicits Broadly Neutralizing Antibodies against Structurally Distinct Domains of H3N2 HA.

Influenza vaccine effectiveness varies annually due to the fast evolving seasonal influenza A(H3N2) strain and egg-derived mutations-both of which can cause a mismatch between the vaccine and circulating strains. To address these limitations, we have developed a hemagglutinin (HA)-based protein-detergent nanoparticle influenza vaccine (NIV) with a saponin-based Matrix-M™ adjuvant. In a phase 1 clinical trial of older adults, the vaccine demonstrated broadly cross-reactive A(H3N2) HA antibody responses. Two broadly neutralizing monoclonal antibodies derived from NIV-immunized mice were characterized by transmission electron microscopy (TEM), antibody competition assays, fluorescence-activated cell sorting (FACS) analysis, and protein-protein docking. These antibodies recognize two conserved regions of the head domain, namely the receptor binding site and the vestigial esterase subdomain, thus demonstrating the potential for an HA subunit vaccine to elicit antibodies targeting structurally and antigenically distinct but conserved sites. Antibody competition studies with sera from the phase 1 trial in older adults confirmed that humans also make antibodies to these two head domains and against the highly conserved stem domain. This data supports the potential of an adjuvanted recombinant HA nanoparticle vaccine to induce broadly protective immunity and improved vaccine efficacy.
Alyse D Portnoff, Nita Patel, Michael J Massare, Haixia Zhou, Jing-Hui Tian, Bin Zhou, Vivek Shinde, Gregory M Glenn, Gale Smith

2506 related Products with: Influenza Hemagglutinin Nanoparticle Vaccine Elicits Broadly Neutralizing Antibodies against Structurally Distinct Domains of H3N2 HA.

10 1 mg50 1 mL100 2 50 101 mL10 110

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#32013187   2020/01/29 To Up

Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin.

The development of recombinant influenza vaccines with broad spectrum protection is an important task. The combination of conservative viral antigens, such as M2e, the extracellular domain of the transmembrane protein M2, and conserved regions of the second subunit of hemagglutinin (HA), provides an opportunity for the development of universal influenza vaccines. Immunogenicity of the antigens could be enhanced by fusion to bacterial flagellin, the ligand for Toll-like receptor 5, acting as a powerful mucosal adjuvant. In this study, we report the transient expression in plants of a recombinant protein comprising flagellin of fused to the conserved region of the second subunit of HA (76-130 a.a.) of the first phylogenetic group of influenza A viruses and four tandem copies of the M2e peptide. The hybrid protein was expressed in plants using the self-replicating potato virus X-based vector pEff up to 300 µg/g of fresh leaf tissue. The intranasal immunization of mice with purified fusion protein induced high levels of M2e-specific serum antibodies and provided protection against lethal challenge with influenza A virus strain A/Aichi/2/68(H3N2). Our results show that M2e and hemagglutinin-derived peptide can be used as important targets for the development of a plant-produced vaccine against influenza.
Elena A Blokhina, Eugenia S Mardanova, Liudmila A Stepanova, Liudmila M Tsybalova, Nikolai V Ravin

2808 related Products with: Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin.

100 1 mg10011 mg200ul100 ug/vial1000100 µg100 µg5001 mL

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#31590935   2019/10/04 To Up

Influenza A and B virus-like particles produced in mammalian cells are highly immunogenic and induce functional antibodies.

Influenza virus-like particles (VLPs) represent an attractive alternative to traditional influenza vaccine formulations. Influenza VLPs mimic the natural virus while lacking the genetic material, are easily recognized by the immune system, and are considered safe. The use of a mammalian cell platform offers many advantages for VLP production, such as flexibility and the same glycosylation patterns as a human virus. In this study, the influenza VLPs containing hemagglutinin (HA), neuraminidase (NA) and matrix M1 proteins were expressed in CHO-K1, Vero or 293 T cell lines using transient transfection. After production in 3L bioreactor and purification, extensive characterization was performed on two batches of VLPs produced in 293 T, the best cell line for VLP expression; one batch expressed the HA and NA genes from A/Hong Kong/4801/2014 (H3N2) strain and the other, HA and NA genes from B/Phuket/3073/2013. Characterizations provided evidence that mammalian VLPs closely emulate the exterior of authentic virus particles in terms of both antigen presentation and biological properties. The two VLPs produced contained more NA proteins on their surface with a HA:NA ratio around 1:1 than influenza viruses which present a HA:NA ratio of around 4:1. Immunogenicity studies in BALB/c mice demonstrated that the VLPs, administered intra-muscularly, were highly immunogenic at low doses, with the induction of functional antibodies against HA and NA. Immunogenicity was also shown in a human in vitro model (MIMIC® system). In conclusion, we believe that influenza vaccines made of VLPs produced in mammalian cell lines, constitute a potential alternative to the classical influenza vaccines.
Sophie Buffin, Isabelle Peubez, Fabienne Barrière, Marie-Claire Nicolaï, Tenekua Tapia, Vipra Dhir, Eric Forma, Nicolas Sève, Isabelle Legastelois

2575 related Products with: Influenza A and B virus-like particles produced in mammalian cells are highly immunogenic and induce functional antibodies.

1 mL1 mg200 100 1 mg100 1000 TESTS/0.65ml1 mL1 mL100 1 mg

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#31565926   2019/09/30 To Up

Generation of Stable Influenza Virus Hemagglutinin through Structure-Guided Recombination.

Hemagglutinin (HA) is the major surface antigen of influenza virus and the most promising influenza vaccine immunogen. In 2013, the devastating H7N9 influenza virus was identified in China, which induced high mortality. The HA of this virus (H7) is relatively unstable, making it challenging to produce an effective vaccine. To improve the stability of HA protein from H7N9 influenza virus for better vaccine antigens without impairing immunogenicity, we recombined the HA from H7N9 (H7) with a more stable HA from H3N2 (H3) by structure-guided recombination, resulting in six chimeric HAs, FrA-FrF. Two of these chimeric HAs, FrB and FrC, exhibited proper hemagglutination activity and presented improved thermal stability compared to the original H7. Mice immunized with FrB and FrC elicited H7-specific antibodies comparable to those induced by parental H7, and the antisera collected from these immunized mice successfully inhibited H7N9 infection in a microneutralization assay. These results suggest that our structural-recombination approach can create stabilizing chimeric antigens while maintaining proper immunogenicity, which may not only benefit the construction of more stable HA vaccines to fight against H7N9 infection, but also facilitate effective vaccine improvements for other influenza viruses or infectious pathogens. In addition, this study also demonstrates the potential for better engineering of multimeric protein complexes like HA to achieve improved function, which are often immunologically or pharmaceutically important but difficult to modify.
Chih-Hsuan Tsai, Sung-Chan Wei, Jia-Tsrong Jan, Lin-Li Liao, Chia-Jung Chang, Yu-Chan Chao

2563 related Products with: Generation of Stable Influenza Virus Hemagglutinin through Structure-Guided Recombination.

10 50 ug2 10 2 1100 100 10 2 1 mg100

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#31375573   2019/08/28 To Up

Extending the Stalk Enhances Immunogenicity of the Influenza Virus Neuraminidase.

Influenza viruses express two surface glycoproteins, the hemagglutinin (HA) and the neuraminidase (NA). Anti-NA antibodies protect from lethal influenza virus challenge in the mouse model and correlate inversely with virus shedding and symptoms in humans. Consequently, the NA is a promising target for influenza virus vaccine design. Current seasonal vaccines, however, poorly induce anti-NA antibodies, partly because of the immunodominance of the HA over the NA when the two glycoproteins are closely associated. To address this issue, here we investigated whether extending the stalk domain of the NA could render it more immunogenic on virus particles. Two recombinant influenza viruses based on the H1N1 strain A/Puerto Rico/8/1934 (PR8) were rescued with NA stalk domains extended by 15 or 30 amino acids. Formalin-inactivated viruses expressing wild-type NA or the stalk-extended NA variants were used to vaccinate mice. The virus with the 30-amino-acid stalk extension induced significantly higher anti-NA IgG responses (characterized by increased antibody-dependent cellular cytotoxicity [ADCC] activity) than the wild-type PR8 virus, while anti-HA IgG levels were unaffected. Similarly, extending the stalk domain of the NA of a recent H3N2 virus enhanced the induction of anti-NA IgGs in mice. On the basis of these results, we hypothesize that the subdominance of the NA can be modulated if the protein is modified such that its height surpasses that of the HA on the viral membrane. Extending the stalk domain of NA may help to enhance its immunogenicity in influenza virus vaccines without compromising antibody responses to HA. The efficacy of influenza virus vaccines could be improved by enhancing the immunogenicity of the NA protein. One of the reasons for its poor immunogenicity is the immunodominance of the HA over the NA in many seasonal influenza virus vaccines. Here we demonstrate that, in the mouse model, extending the stalk domain of the NA protein can enhance its immunogenicity on virus particles and overcome the immunodominance of the HA without affecting antibody responses to the HA. The antibody repertoire is broadened by the extended NA and includes additional ADCC-active antibodies. Our findings may assist in the efforts toward more effective influenza virus vaccines.
Felix Broecker, Allen Zheng, Nungruthai Suntronwong, Weina Sun, Mark J Bailey, Florian Krammer, Peter Palese

2415 related Products with: Extending the Stalk Enhances Immunogenicity of the Influenza Virus Neuraminidase.

100 500 1 mg100 IU0.1 mg100 1 mg500 Units1 ml25

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#31296560   2019/07/11 To Up

Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics.

Several next-generation (universal) influenza vaccines and broadly neutralizing antibodies (bNAbs) are in clinical development. Some of these mediate inhibitions of virus replication at the postentry stage or use Fc-dependent mechanisms. Nonneutralizing antibodies have the potential to mediate enhancement of viral infection or disease. In the current study, two monoclonal antibodies (MAbs) 72/8 and 69/1, enhanced respiratory disease (ERD) in mice following H3N2 virus challenge by demonstrating increased lung pathology and changes in lung cytokine/chemokine levels. MAb 78/2 caused changes in the lung viral loads in a dose-dependent manner. Both MAbs increased HA sensitivity to trypsin cleavage at a higher pH range, suggesting MAb-induced conformational changes. pHrodo-labeled virus particles' entry and residence time in the endocytic compartment were tracked during infection of Madin-Darby canine kidney (MDCK) cells. Both MAbs reduced H3N2 virus residence time in the endocytic pathway, suggesting faster virus fusion kinetics. Structurally, 78/2 and 69/1 Fabs bound the globular head or base of the head domain of influenza hemagglutinin (HA), respectively, and induced destabilization of the HA stem domain. Together, this study describes Mab-induced destabilization of the influenza HA stem domain, faster kinetics of influenza virus fusion, and ERD in vivo. The in vivo animal model and in vitro assays described could augment preclinical safety evaluation of antibodies and next-generation influenza vaccines that generate antibodies which do not block influenza virus-receptor interaction.
Katie L Winarski, Juanjie Tang, Laura Klenow, Jeehyun Lee, Elizabeth M Coyle, Jody Manischewitz, Hannah L Turner, Kazuyo Takeda, Andrew B Ward, Hana Golding, Surender Khurana

1235 related Products with: Antibody-dependent enhancement of influenza disease promoted by increase in hemagglutinin stem flexibility and virus fusion kinetics.

100 10 2 10 100 2 10 50 ug12 1 mg100

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#31147904   2019/05/28 To Up

Development and optimized pairing of mouse monoclonal antibodies for detecting hemagglutinin in novel H7 subtype influenza viruses.

The H7 subtype avian influenza threatens public health with respect to poultry and humans. Thus, a specific and sensitive diagnostic test is essential for the management of H7 subtype influenza infections. In this study, five mouse monoclonal antibodies (mAbs) against hemagglutinin (HA) of influenza A/Anhui/1/2013 (H7N9) were produced and characterized by the Western blot, immunofluorescence, and hemagglutination inhibition assays. All five specific mAbs reacted with the HA protein of H7N9 but not with that of H1N1, H3N2, or H5N1. With the combination arrays of capture and detection antibodies, the matched pair mAbs (1C4-coated and 2D7-labeled) were selected and employed in a double-antibody sandwich ELISA (DAS-ELISA). Detection limits of the sandwich ELISA were 0.45 ng mL for the HA protein derived from A/Anhui/1/2013 (H7N9); or 1 and 2 HA units/50 µL for A/Anhui/1/2013 (H7N9) and A/GD/17SF003/2016 (H7N9), respectively. These anti-HA mAbs against subtype H7 and the novel DAS-ELISA provide a valuable approach for specific detection of the H7 subtype influenza virus and quantification of its HA protein, especially for the novel epidemic H7N9.
Huijuan Wang, Jianfang Zhou, Dayan Wang, Baoying Huang, Wenjie Tan

1978 related Products with: Development and optimized pairing of mouse monoclonal antibodies for detecting hemagglutinin in novel H7 subtype influenza viruses.

1 mg100 ug100.00 ug50 200 100.00 ug100.00 ug0.2 mg100 100.00 ug100.00 ug100.00 ug

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#31104946   2019/05/16 To Up

Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope.

Viral glycoproteins are under constant immune surveillance by a host's adaptive immune responses. Antigenic variation including glycan introduction or removal is among the mechanisms viruses have evolved to escape host immunity. Understanding how glycosylation affects immunodominance on complex protein antigens may help decipher underlying B cell biology. To determine how B cell responses can be altered by such modifications, we engineered glycans onto the influenza virus hemagglutinin (HA) and characterized the molecular features of the elicited humoral immunity in mice. We found that glycan addition changed the initially diverse antibody repertoire into an epitope-focused, genetically restricted response. Structural analyses showed that one antibody gene family targeted a previously subdominant, occluded epitope at the head interface. Passive transfer of this antibody conferred Fc-dependent protection to influenza virus-challenged mice. These results have potential implications for next-generation viral vaccines aimed at directing B cell responses to preferred epitope(s).
Goran Bajic, Max J Maron, Yu Adachi, Taishi Onodera, Kevin R McCarthy, Charles E McGee, Gregory D Sempowski, Yoshimasa Takahashi, Garnett Kelsoe, Masayuki Kuraoka, Aaron G Schmidt

1081 related Products with: Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope.

1100 ug/vial1 kit(96 Wells)100 ug100 ug/vial1 kit(96 Wells)1 kit(96 Wells)100 µg1 mg100ug/vial1mg100

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#31100268   // To Up

A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.

Here, we describe the discovery of a naturally occurring human antibody (Ab), FluA-20, that recognizes a new site of vulnerability on the hemagglutinin (HA) head domain and reacts with most influenza A viruses. Structural characterization of FluA-20 with H1 and H3 head domains revealed a novel epitope in the HA trimer interface, suggesting previously unrecognized dynamic features of the trimeric HA protein. The critical HA residues recognized by FluA-20 remain conserved across most subtypes of influenza A viruses, which explains the Ab's extraordinary breadth. The Ab rapidly disrupted the integrity of HA protein trimers, inhibited cell-to-cell spread of virus in culture, and protected mice against challenge with viruses of H1N1, H3N2, H5N1, or H7N9 subtypes when used as prophylaxis or therapy. The FluA-20 Ab has uncovered an exceedingly conserved protective determinant in the influenza HA head domain trimer interface that is an unexpected new target for anti-influenza therapeutics and vaccines.
Sandhya Bangaru, Shanshan Lang, Michael Schotsaert, Hillary A Vanderven, Xueyong Zhu, Nurgun Kose, Robin Bombardi, Jessica A Finn, Stephen J Kent, Pavlo Gilchuk, Iuliia Gilchuk, Hannah L Turner, Adolfo García-Sastre, Sheng Li, Andrew B Ward, Ian A Wilson, James E Crowe

1708 related Products with: A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface.

100 1251 mL10 50 1 mL1 mg1 mg200 100 2

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