Universal and reusable virus deactivation system for respiratory protection

Fu-Shi Quan, Ilaria Rubino, Su-Hwa Lee, Brendan Koch, Hyo-Jick Choi, Fu-Shi Quan, Ilaria Rubino, Su-Hwa Lee, Brendan Koch, Hyo-Jick Choi

Abstract

Aerosolized pathogens are a leading cause of respiratory infection and transmission. Currently used protective measures pose potential risk of primary/secondary infection and transmission. Here, we report the development of a universal, reusable virus deactivation system by functionalization of the main fibrous filtration unit of surgical mask with sodium chloride salt. The salt coating on the fiber surface dissolves upon exposure to virus aerosols and recrystallizes during drying, destroying the pathogens. When tested with tightly sealed sides, salt-coated filters showed remarkably higher filtration efficiency than conventional mask filtration layer, and 100% survival rate was observed in mice infected with virus penetrated through salt-coated filters. Viruses captured on salt-coated filters exhibited rapid infectivity loss compared to gradual decrease on bare filters. Salt-coated filters proved highly effective in deactivating influenza viruses regardless of subtypes and following storage in harsh environmental conditions. Our results can be applied in obtaining a broad-spectrum, airborne pathogen prevention device in preparation for epidemic and pandemic of respiratory diseases.

Figures

Figure 1. Mask with salt-coated filter for…
Figure 1. Mask with salt-coated filter for prevention and deactivation of airborne pathogens.
(a) SEM image of Filterwet+600μL (top left) and EDX mapping images of Na (red), Cl (green), and NaCl (combination of Na and Cl mapping images), showing the formation of NaCl coating, as also confirmed by XRD spectra (b) of Filterbare, Filterwet, Filterwet+100μL, Filterwet+300μL, Filterwet+600μL, Filterwet+900μL and Filterwet+1200μL (labelled as Bare, wet, wet+100 μL, wet+300 μL, wet+600 μL, wet+900 μL and wet+1200 μL, respectively; miller indices corresponding to NaCl crystal are shown at the top of XRD spectra for each position). (c) Optical microscope images for contact angle measurements using 3 μL DI water droplets on (i) Filterbare and (ii) Filterwet+600μL (n = 10). (d) Microscope images of aerosol on (i) Filterbare and (ii) Filterwet+600μL (n = 10).
Figure 2. Filtration efficiency of salt-coated filters.
Figure 2. Filtration efficiency of salt-coated filters.
(a) TEM image of CA/09 H1N1 influenza virus. (b) Pressure-dependent filtration efficiency (n = 8–10, mean ± standard deviation (SD)). (c–f) Effects of filtration efficiency on protective efficacy in vivo. Body weight change of mice after infection with the dosages of penetrated virus (n = 12, mean ± SD) (c), survival rates (mean; 100% means that all mice in the group survived as penetrated dosages were lower than lethal dose) (d), lung virus titers (n = 4, mean ± SD) (e), and lung inflammatory cytokine (interferon-γ (IFN-γ)) assay (n = 11, mean ± SD) (f). Legends: filters are labelled as in Fig. 1b.
Figure 3. Inactivation of virus adsorbed on…
Figure 3. Inactivation of virus adsorbed on salt-coated filters.
(a,b) HA activity (a) and virus titer (b) displaying the effects of incubation time on the remaining activity of virus (n = 4–8, mean ± SD). (c) TEM images of viruses reconstituted, after incubation for 5 and 60 min, from (i) Filterbare and (ii) Filterwet+600μL. (d) Native fluorescence/nile red fluorescence of viruses incubated for 60 min (n = 12, mean ± SD). (e,f) Body weight change of mice after infection with virus recovered from filters after incubation for 60 min (n = 12, mean ± SD) (e), and lung virus titers (n = 6, mean ± SD) (f). Asterisk (*): below detection limit. Legends: filters are labelled as in Fig. 1b.
Figure 4. Strain- and environment-dependent performance of…
Figure 4. Strain- and environment-dependent performance of salt-coated filters.
(a) Body weight change of mice infected with penetrated PR/34 H1N1 and VN/04 H5N1 viruses through Filterwet+600μL (n = 12, mean ± SD). (b) Virus titers of recovered viruses from bare and salt-coated filters (n = 4, mean ± SD; data for Filterwet, Filterwet+600μL and Filterwet+1200μL are overlapped). (c,d) Body weight change (c) and survival rate (d) of mice infected with dosage of penetrated virus through Filterwet+600μL before and after exposure to harsh environmental conditions (37 °C and 70% RH) for 1 day (filled square and open square overlap in (d)). (e) EDX mapping image of NaCl-coated Filterwet+600μL after incubation for 15 days at 37 °C and 70% RH (combination of Na (red) and Cl (green) mapping images). (f) XRD spectra of Filterwet+600μL before and after incubation at 37 °C 70% for 1 day and 15 days. Legends: filters are labelled as in Fig. 1b.

References

    1. Tellier R. Review of aerosol transmission of influenza A virus. Emerging Infect. Dis. 12, 1657–1662 (2006).
    1. Weber T. P. & Stilianakis N. I. Inactivation of influenza A viruses in the environment and modes of transmission: a critical review. J. Infect. 57, 361–373 (2008).
    1. Duy J. et al.. Circulating microRNA profiles of Ebola virus infection. Sci. Rep. 6, 24496 (2016).
    1. Morse S. S., Garwin R. L. & Olsiewski P. J. Next flu pandemic: what to do until the vaccine arrives? Science 314, 929–929 (2006).
    1. CDC. Laboratory performance evaluation of N95 filtering facepiece respirators, 1996. MMWR, Morbidity and Mortality Weekly Report 47, 1045 (1998).
    1. Seto W. H. et al.. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet 361, 1519–1520 (2003).
    1. Bałazy A. et al.. Do N95 respirators provide 95% protection level against airborne viruses, and how adequate are surgical masks? Am. J. Infect. Control 34, 51–57 (2006).
    1. Loeb M. et al.. Surgical mask vs N95 respirator for preventing influenza among health care workers: a randomized trial. JAMA 302, 1865–1871 (2009).
    1. Bunyan D., Ritchie L., Jenkins D. & Coia J. E. Respiratory and facial protection: a critical review of recent literature. J. Hosp. Infect. 85, 165–169 (2013).
    1. Zhu C., Lin C. H. & Cheung C. S. Inertial impaction-dominated fibrous filtration with rectangular or cylindrical fibers. Powder Technol. 112, 149–162 (2000).
    1. Lee K. W. & Liu B. Y. H. Theoretical study of aerosol filtration by fibrous filters. Aerosol Sci. Tech. 1, 147–161 (1982).
    1. Duarte Fo, O. B., Marra W. D., Kachan G. C. & Coury J. R. Filtration of electrified solid particles. Ind. Eng. Chem. Res 39, 3884–3895 (2000).
    1. Kraemer H. F. & Johnstone H. F. Collection of aerosol particles in presence of electrostatic fields. Ind. Eng. Chem. 47, 2426–2434 (1955).
    1. Ranz W. E. & Wong J. B. Impaction of dust and smoke particles on surface and body collectors. Ind. Eng. Chem. 44, 1371–1381 (1952).
    1. Siegel J. D., Rhinehart E., Jackson M. & Chiarello L. 2007 guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am. J. Infect. Control 35, S65–S164 (2007).
    1. Coia J. E. et al.. Guidance on the use of respiratory and facial protection equipment. J. Hosp. Infect. 85, 170–182 (2013).
    1. Ratnesar-Shumate S. et al.. Evaluation of physical capture efficiency and disinfection capability of an iodinated biocidal filter medium. Aerosol Air Qual. Res. 8, 1–18 (2008).
    1. Lee J. H., Wu C. Y., Wysocki K. M. & Farrah S. & Wander, J. Efficacy of iodine-treated biocidal filter media against bacterial spore aerosols. J. Appl. Microbiol. 105, 1318–1326 (2008).
    1. Badrossamay M. R. & Sun G. Acyclic halamine polypropylene polymer: effect of monomer structure on grafting efficiency, stability and biocidal activities. React. Funct. Polym. 68, 1636–1645 (2008).
    1. Zhao N. & Liu S. Thermoplastic semi-IPN of polypropylene (PP) and polymeric N-halamine for efficient and durable antibacterial activity. Eur. Polym. J. 47, 1654–1663 (2011).
    1. Cerkez I., Worley S. D., Broughton R. M. & Huang T. S. Antimicrobial surface coatings for polypropylene nonwoven fabrics. React. Funct. Polym. 73, 1412–1419 (2013).
    1. Davison A. M. Pathogen inactivation and filtration efficacy of a new anti-microbial and anti-viral surgical facemask and N95 against dentistry-associated microorganisms. International dentistry Australasian edition 7, 36–42 (2012).
    1. Borkow G., Zhou S. S., Page T. & Gabbay J. A novel anti-influenza copper oxide containing respiratory face mask. PLoS One 5, e11295 (2010).
    1. Borkow G. & Gabbay J. Putting copper into action: copper-impregnated products with potent biocidal activities. FASEB J. 18, 1728–1730 (2004).
    1. Li Y., Leung P., Yao L., Song Q. W. & Newton E. Antimicrobial effect of surgical masks coated with nanoparticles. J. Hosp. Infect. 62, 58–63 (2006).
    1. Lee J. H. et al.. Assessment of iodine-treated filter media for removal and inactivation of MS2 bacteriophage aerosols. J. Appl. Microbiol. 107, 1912–1923 (2009).
    1. Lore M. B. et al.. Performance of conventional and antimicrobial-treated filtering facepiece respirators challenged with biological aerosols. J. Occup. Environ. Hyg. 9, 69–80 (2012).
    1. Rengasamy S., Fisher E. & Shaffer R. E. Evaluation of the survivability of MS2 viral aerosols deposited on filtering face piece respirator samples incorporating antimicrobial technologies. Am. J. Infect. Control 38, 9–17 (2010).
    1. Windisch W., Hennings E., Sorichter S., Hamm H. & Criee C. P. Peak or plateau maximal inspiratory mouth pressure: which is best? Eur. Respir. J. 23, 708–713 (2004).
    1. Choi H.-J. et al.. Stability of influenza vaccine coated onto microneedles. Biomaterials 33, 3756–3769 (2012).
    1. Choi H.-J. et al.. Stability of whole inactivated influenza virus vaccine during coating onto metal microneedles. J. Control. Release 166, 159–171 (2013).
    1. Baldwin R. L. How hofmeister ion interactions affect protein stability. Biophys. J. 71, 2056–2063 (1996).
    1. Choi H.-J. et al.. Effect of osmotic pressure on the stability of whole inactivated influenza vaccine for coating on microneedles. PLoS one 10, e0134431 (2015).
    1. ASTM International. ASTM F2101 - 14 Standard Test Method for Evaluating the Bacterial Filtration Efficiency (BFE) of Medical Face Mask Materials, Using a Biological Aerosol of Staphylococcus aureus (2014).
    1. Adams J. R. & Merz A. R. Hygroscopicity of fertilizer materials and mixtures. Ind. Eng. Chem. Res. 21, 305–307 (1929).
    1. Song J.-M. et al.. Protective immunity against H5N1 influenza virus by a single dose vaccination with virus-like particles. Virology 405, 165–175 (2010).
    1. Quan F. S. et al.. A bivalent influenza VLP vaccine confers complete inhibition of virus replication in lungs. Vaccine 26, 3352–3361 (2008).
    1. Choi H.-J., Ebersbacher C. F., Kim M., Kang S. & Montemagno C. D. A mechanistic study on the destabilization of whole inactivated influenza virus vaccine in gastric environment. PLoS one 8, e66316 (2013).
    1. Greenspan P., Mayer E. P. & Fowler S. D. Nile red: a selective fluorescent stain for intracellular lipid droplets. J. Cell Biol. 100, 965–973 (1985).

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe