Microban can, through a network of global labs, conduct antiviral testing for developmental products. Due to the high cost of antiviral testing, we work carefully with prospects to ensure that commercial interests are fully understood.

Microban antiviral technologies are durable and always-on treatments. For wearable articles, it is best to minimize washing to maintain the best levels of performance and sustainability.

Many of our antiviral technologies do not affect the skin as they do not interfere with its natural bacterial flora. Microban antiviral technologies are incorporated at the point of manufacture, as close to the finishing stage of production as possible. No additional water or energy is needed, and therefore the impact on the environment is reduced.

When you partner with Microban, we will help you craft acceptable antiviral claims language for your specific countries of sale. There are strict regulatory requirements in the US, Canada, and Europe for making health claims.

This could be a multi-year investment that is resource-intensive. There can be alternative routes that do not require this approach.

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Home Antiviral Antiviral Technologies. Antiviral Technologies Microban® is pleased to announce a new range of antiviral technologies that are proven to reduce viral loading on products and surfaces.

Technology Overview. Regulatory Considerations for North America. What are the regulatory considerations for North America? See below for more info. Regulatory Considerations for Europe.

What are the regulatory considerations for Europe? Antiviral Technology Applications. What are typical applications for antiviral technologies? Frequently Asked Questions. Frequently Asked Questions See below for more info. How does antiviral technology differ from antimicrobial technology?

What are the benefits of Microban antiviral technologies? When Microban developed our antiviral technology suite, we had two criteria we wanted to fulfil: We wanted to be able to show a real antiviral effect that could be tested by a standard method to allow our partners to make claims in the marketplace, and We wanted to be able to take these solutions to a broad set of partners in all geographies to maximize the impact of the antiviral treatment on their products.

How do Microban antiviral technologies work? Polymers are widely used because they can be shatter-resistant, stretchable, and flexible, making them useful for various functions.

Many polymers have been used for antiviral composite materials in which the antiviral agents are encapsulated in polymers to form antiviral composites. The final pH was adjusted to between 6. Formulations were filtered using a 0.

This screening approach could underestimate the total number of target-specific mAbs in the panel but enabled the elimination of poorly produced mAbs. For dose—response assays, serial dilutions of purified mAbs were applied to the wells in triplicate or quadruplicate, and mAb binding was detected as described above.

ZIKV-infected cell foci were visualized using TrueBlue peroxidase substrate KPL and quantified on an ImmunoSpot 5. Data were analysed using ForeCyt v. To screen for neutralizing activity in the panel of recombinantly expressed mAbs, we used a high-throughput and quantitative RTCA assay and xCelligence Analyzer ACEA Biosciences that assesses kinetic changes in cell physiology, including virus-induced CPE.

For the screening neutralization assay, the virus multiplicity of infection, 0. Wells containing virus only in the absence of mAbs and wells containing only Vero cells in medium were included as controls.

A mAb was considered to be neutralizing if it partially or completely inhibited ZIKV-induced CPE. IC 50 values were estimated as the change in cellular index over time, using nonlinear fit with variable slope analysis performed in the RTCA v.

The potency ranking study was repeated using midi-scale-purified mAbs to confirm the activity and to ensure the quality of antibody preparations before performing in vivo protection studies in mice.

Recombinant soluble ZIKV E protein was biotinylated and coupled to Alexa-Fluordye-coupled Neutravidin beads Life Technologies. Microscale-purified mAbs were tested at a single dilution; concentrations were not normalized. THP-1 cells ATCC were added at 2.

of the population. The human mAb ZIKV was used as a positive control, and the human mAb FLU-5J8 was used as a negative control.

Recombinant soluble ZIKV E protein was biotinylated and coupled to Alexa-Fluor-dye-coupled Neutravidin beads Life Technologies.

White blood cells were isolated from the peripheral blood of participants by lysis of red blood cells, followed by three washes with PBS. Cells were added at a concentration of 5. Z -score values were calculated as described above.

The previously identified mAb ZIKV was used as a positive control, and the mAb FLU-5J8 was used as a negative control. Recombinant soluble ZIKV E protein was biotinylated and coupled to red fluorescent Neutravidin beads Life Technologies. Freshly reconstituted guinea pig complement Cedarlane Labs was diluted in veronal buffer with 0.

Plates were washed, and the bound antibodies were detected using HRP-conjugated avidin Sigma and TMB substrate. The signal obtained for binding of the biotin-labelled reference antibody in the presence of the unlabelled tested antibody was expressed as the percentage of the binding of the reference antibody alone after subtracting the background signal.

Epitope mapping was performed using shotgun mutagenesis essentially as described previously Antibodies were detected using 3. Mean cellular fluorescence was detected using a high-throughput flow cytometer HTFC, Intellicyt. Mutations within clones were identified to be critical to the mAb epitope if they did not support reactivity of the test MAbs, but supported reactivity of other ZIKV antibodies.

The amount of human mAbs in serum was detected using a capture ELISA with a standard curve of recombinant anti-ZIKV mAb ZIKV or an IgG1 isotype-matched control anti-influenza mAb, FLU-5J8. Plates were developed using TMB substrate Thermo Fisher Scientific , and the reaction was stopped with H 2 SO 4.

ELISA plates were read using a TriBar LB plate reader Berthold Technologies. The optical density values from the known quantity of ZIKV were fitted to a standard curve and compared with the optical density values of serum to determine the concentration of ZIKV The antibodies ZIKV, ZIKV and ZIKV failed to perform in this detection assay, even in cases in which they were used as purified IgG.

Serum concentration measurements for these mAbs are not available. Blood was collected from ZIKV-infected mice at various time points, allowed to clot at ambient temperature and serum was separated using centrifugation. Viral RNA was isolated using the well Viral RNA kit Epigenetics , as described by the manufacturer.

ZIKV RNA levels were determined using TaqMan one-step RT—qPCR as described previously Alternatively, ZIKV Dakar MA and Brazil strain titres were determined using a focus-forming assay on Vero cell monolayer cultures, as previously described For the prophylaxis experiments, mice were treated i.

For the therapeutic protection experiments, mice were treated i. For ZIKV infections, mice were inoculated by a s. The antibody ZIKV was used as a positive control, and the mAb FLU-5J8 or PBS was used as a negative control.

The rhesus macaques were aged 5—7 years and were mixed male and female. All of the animals were inoculated by the s. route with a target dose of 10 6 viral particles ~10 3 p. of ZIKV Brazil before mAb infusions. All of the animals were given physical exams, and blood was collected at the time of ZIKV inoculation and at indicated times after ZIKV inoculation.

Furthermore, all of the animals were monitored daily with an internal scoring protocol approved by the Institutional Animal Care and Use Committee. These studies were not performed blinded.

Titration of virus in the indicated specimens was performed using RT—qPCR analysis as previously described 47 , Viral RNA was isolated from plasma and other tested specimens using a QIAcube HT QIAGEN system.

A QIAcube 96 Cador Pathogen kit or RNeasy 96 QIAcube HT kit was used for RNA extraction. cDNA of the wild-type BeH Cap gene was cloned into the pcDNA3. RNA quality was assessed by the Beth Israel Deaconess Medical Center molecular core facility.

Tenfold dilutions of the RNA were prepared for standards and reverse transcribed to cDNA. Primers were synthesized by Integrated DNA Technologies Coralville , and probes were obtained from Biosearch Technologies Petaluma.

Viral loads were calculated as virus particles per ml, and the assay sensitivity was copies per ml. A modified protocol using the commercially available human anti-ZIKV-Env IgG kit Alpha Diagnostics International was used to quantify ZIKV mAb levels in NHP serum samples.

A four-parameter logistic standard curve was generated using Prism v. were determined for continuous variables as noted.

Survival curves were estimated using the Kaplan—Meier method, and an overall difference between groups was estimated using the two-sided log-rank Mantel—Cox test. In the neutralization assays using focus-reduction neutralization tests, IC 50 values were calculated after log transformation of antibody concentrations using a three-parameter nonlinear fit analysis.

In the RTCA neutralization assays, IC 50 values were estimated as cellular index change over time using nonlinear fit with variable slope analysis determined in the RTCA v. Technical and biological replicates are described in the figure legends. Statistical analyses were performed using Prism v.

Further information on research design is available in the Nature Research Reporting Summary linked to this article. The main data supporting the results in this study are available within the paper and its Supplementary Information.

The raw and analysed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request.

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A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes. Immunology , 13—20 Govero, J. Zika virus infection damages the testes in mice. Lazear, H. A mouse model of Zika virus pathogenesis. Cell Host Microbe 19 , — Download references. We thank M. Mayo for assistance with acquisition of the human survivor samples and coordination across study sites; J.

Govero for assistance with RNA protection experiments; A. Jones and K. Beeri for assistance and coordination of NGS sequencing timelines; J. Slaughter, M. Goff and R. Troseth for assistance with data analysis; and STEMCELL Technologies and ACEA Biosciences for providing resources. This study was supported by Defense Advanced Research Projects Agency DARPA grant HR and HHS contract HHSNC to J.

and B. The content is solely the responsibility of the authors and does not necessarily represent the official views of the DARPA. These authors contributed equally: Pavlo Gilchuk, Robin G. Bombardi, Jesse H.

Erasmus, Qing Tan, Rachel Nargi, Cinque Soto, Peter Abbink, Todd J. Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA. Pavlo Gilchuk, Robin G. Bombardi, Rachel Nargi, Cinque Soto, Taylor Jones, James E. Pre-Clinical Vaccine Development, Infectious Disease Research Institute, Seattle, WA, USA.

Jesse H. Erasmus, Amit Khandhar, Jacob Archer, Elise Larson, Stacey Ertel, Brian Granger, Jasmine Fuerte-Stone, Steven G. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA. Qing Tan, Lorellin A. Durnell, Michael S. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. Todd J. Suscovich, Vicky Roy, Thomas Broge, Thomas C. Linnekin, Caitlyn H.

Linde, Matthew J. Jenny Liang, Mallorie E. Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO, USA.

Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis, MO, USA. Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.

Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN, USA. Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA. You can also search for this author in PubMed Google Scholar.

and R. planned the studies. and J. conducted experiments. interpreted the studies. wrote the first draft of the paper. obtained funding. All of the authors reviewed, edited and approved the paper. Correspondence to Neal Van Hoeven , Larissa B.

Thackray or Robert H. are employees of Integral Molecular. is a shareholder of Integral Molecular. has a financial interest in SeromYx, a company developing technology that describes the antibody immune response.

interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. is a consultant for Inbios and Emergent BioSolutions and on the Scientific Advisory Board of Moderna.

has served as a consultant for Sanofi and is on the Scientific Advisory Boards of CompuVax and Meissa Vaccines, is a recipient of previous unrelated research grants from Moderna and Sanofi and is the founder of IDBiologics.

and N. are listed as inventors on a patent application describing the NLC formulation. Vanderbilt University has applied for a patent US Provisional Patent no.

The other authors declare no competing interests. Reprints and permissions. Integrated pipeline for the accelerated discovery of antiviral antibody therapeutics. Nat Biomed Eng 4 , — Download citation. Received : 09 March Accepted : 26 June Published : 03 August Issue Date : November Anyone you share the following link with will be able to read this content:.

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nature nature biomedical engineering articles article. Download PDF. Subjects Antibodies Biologics Nucleic-acid therapeutics Viral infection. Abstract The emergence and re-emergence of highly virulent viral pathogens with the potential to cause a pandemic creates an urgent need for the accelerated discovery of antiviral therapeutics.

A pandemic-enabled comparison of discovery platforms demonstrates a naïve antibody library can match the best immune-sourced antibodies Article Open access 24 January Antibodies to combat viral infections: development strategies and progress Article 20 June Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies Article Open access 23 December Main Human monoclonal antibodies mAbs are increasingly being considered for use as therapeutic countermeasures against viral infectious diseases.

Full size image. Results Virus stock production We used a contemporary ZIKV strain of the Asian lineage Brazil, Paraiba and a historical ZIKV strain of the African lineage Dakar, Senegal to account for genetic diversity and, ultimately, breadth of protection.

Antibody variable gene sequence analysis and bioinformatics processing To model a rapid response to a previously known pathogen, we used a mAb discovery approach, assuming that the envelope protein ZIKV E protein on the virion surface is a key protective antigen 5 , 6 , 21 , Table 1 Summary of binding and functional activities of 20 characterized lead mAbs Full size table.

Discussion Here we described an integrated technology modelling deployment of the rapid response for discovering of antiviral antibodies.

Methods Research participants We studied 11 participants in the United States with previous or recent ZIKV infection and one uninfected control participant Supplementary Table 1.

Animals The mouse challenge studies were approved by the Washington University School of Medicine assurance number, A Institutional Animal Care and Use Committee.

Virus stock production To identify cells suitable for the production of high-titre ZIKV stocks in an antigen-independent manner, we used RT—qPCR to rapidly detect ZIKV viral RNA in a panel of immortalized cell lines, including those that are commonly used for virus propagation: Vero-E6 ATCC , BHK ATCC , JEG-3 ATCC , HeLa ATCC , HEKT ATCC , U2OS ATCC , A ATCC , Huh7, Huh7.

Human participant selection and target-specific B mem -cell isolation B-cell responses to ZIKV in PBMCs from a cohort of 11 individuals with previous exposure to the ZIKV Asian lineage were assessed to identify individuals with the highest response.

Generation of single-cell antibody variable gene profiling libraries The Chromium Single Cell V D J workflow with the B-cell-only enrichment option was chosen for generating linked heavy-chain and light-chain antibody profiling libraries.

Bioinformatics analysis Down-selection to identify lead candidates for expression was performed in two phases. Antibody-gene synthesis Sequences of selected mAbs were synthesized using a rapid high-throughput cDNA synthesis platform Twist Bioscience and subsequently cloned into an IgG1 monocistronic expression vector designated as pTwist for mammalian cell culture mAb secretion.

MAb production and purification For high-throughput production of recombinant mAbs, we used approaches that are designated as microscale.

Production of antibody-encoding RNA cDNAs encoding the 20 lead mAb candidates were amplified from the mammalian expression pTwist vector using universal primer sets and cloned into plasmids encoding Venezuelan equine encephalitis virus replicon strain TC under the control of a T7 promoter pT7-VEE-Rep RNA formulation production The NLC nanoparticle formulation was manufactured as previously described RTCA To screen for neutralizing activity in the panel of recombinantly expressed mAbs, we used a high-throughput and quantitative RTCA assay and xCelligence Analyzer ACEA Biosciences that assesses kinetic changes in cell physiology, including virus-induced CPE.

Antibody-mediated cellular phagocytosis by human monocytes Recombinant soluble ZIKV E protein was biotinylated and coupled to Alexa-Fluordye-coupled Neutravidin beads Life Technologies. Antibody-mediated neutrophil phagocytosis Recombinant soluble ZIKV E protein was biotinylated and coupled to Alexa-Fluor-dye-coupled Neutravidin beads Life Technologies.

Antibody-mediated complement deposition Recombinant soluble ZIKV E protein was biotinylated and coupled to red fluorescent Neutravidin beads Life Technologies. Detection of circulating human mAbs in mouse serum The amount of human mAbs in serum was detected using a capture ELISA with a standard curve of recombinant anti-ZIKV mAb ZIKV or an IgG1 isotype-matched control anti-influenza mAb, FLU-5J8.

ZIKV titre measurements Blood was collected from ZIKV-infected mice at various time points, allowed to clot at ambient temperature and serum was separated using centrifugation. Detection of virus load in NHPs by RT—qPCR analysis Titration of virus in the indicated specimens was performed using RT—qPCR analysis as previously described 47 , Detection of circulating human mAbs in NHP serum A modified protocol using the commercially available human anti-ZIKV-Env IgG kit Alpha Diagnostics International was used to quantify ZIKV mAb levels in NHP serum samples.

Reporting Summary Further information on research design is available in the Nature Research Reporting Summary linked to this article. Data availability The main data supporting the results in this study are available within the paper and its Supplementary Information. Code availability The 10x Genomics Cell Ranger v.

References Sok, D. CAS Google Scholar Laursen, N. CAS Google Scholar Bornholdt, Z.