WO1999032707A1

WO1999032707A1 - Materials for virus capture

Info

Publication number: WO1999032707A1
Application number: PCT/GB1998/003873
Authority: WO
Inventors: Ian Alexander Mckay; John Sidney Oxford; Robert Lambkin
Original assignee: Retroscreen Limited
Priority date: 1997-12-22
Filing date: 1998-12-22
Publication date: 1999-07-01
Also published as: EP1042551A1; AU1773099A; JP2001527166A; GB9727119D0

Abstract

A fibrous material which comprises a plurality of interwoven threads with a high degree of microfibrillation wherein at least one thread is derivatised using cyanogen bromide to attach a natural receptor for a virus, or a portion or an analogue thereof to capture a virus.

Description

MATERIALS FOR VIRUS CAPTURE

The present invention relates to materials for virus capture and their use as filters or as components of protective articles of clothing which have been manufactured to prevent or reduce transmission of viruses to the wearer thus providing a degree of protection from infection.

Viral infection is a significant cause of disease and ill-health in animals. Viruses are generally classified according to their nucleic acid content and morphology. For example, DNA viruses may be classified as envelope double-stranded, envelope single-stranded or non-enveloped double stranded. The RNA viruses can be similarly classified as envelope single-stranded, non-enveloped double stranded or non-enveloped single-stranded (Wansbrough-Jones et al in Textbook of Medicine, 208-319, Second Edition, edited by Souhami, R.L. , & Moxham, J., Churchill Livingstone (1994)).

The Orthomyxo virus family of RNA viruses comprise Influenza types A, B and C, and the viruses are enveloped single-stranded. Influenza A virus and influenza B virus cause significant problems each winter in communities throughout the world and the mortality rates may be high even in countries such as the UK where a vaccine is distributed to the "at risk" groups (Stuart-Harris, Schild and Oxford in Influenza: the virus and the disease, published by Edward Arnold, London (1985)). Although the disease is normally mild and self limiting, the elderly and those with chronic chest disease are susceptible to complications resulting in considerable mortality. The elderly are more vulnerable to all complications. The most common is exacerbation of chronic bronchitis and this is responsible for most adult admissions to hospital in influenza epidemics. Asthma is also exacerbated. Bacterial pneumonia, often caused by S. pneumoniae, S. aureus or H. influenzae can occur in chronic bronchitics or patients with no history of chest disease. Viral pneumonia caused by influenza virus itself is a severe complication which usually occurs in patients with underlying chest or cardio-vascular disease. Other rarer complications include, myositis, myocarditis, pericarditis, Guillain-Barre syndrome and encephalitis (Wansbrough-Jones et al in Textbook of Medicine, 208-319, Second Edition, edited by Souhami, R.L., & Moxham, J., Churchill Livingstone (1994))..

In 1996, the number of deaths among the elderly from influenza in the UK were almost 18,000. Pandemics have occurred infrequently over the last century in 1889, 1918, 1957, 1968 and 1977. They result from the emergence of new viruses in which there are major changes in the surface proteins, mainly neuraminidase and haemagglutinin, against which the populations of the world have no immunity. The mechanism for these changes is likely to be genetic reassortment and some evidence suggests that this occurs in animal reservoirs, such as birds and lower mammals, especially chickens and pigs. Two neuraminidases and three haemagglutinins have been detected at various times in the last century in human influenza viruses and these are recognised in the name given to a sub-type of virus. For example, the virus responsible for the 1918 epidemic was H1N1 and another sever epidemic in 1957 was caused by H2N2. The severity of an outbreak is determined by the extent of change in antigenicity of the virus so that if the neuraminidase and the haemagglutinin both undergo a major change, the severity of disease and the size of the epidemic are greater than if only one determinant changes. After a major antigenic shift causing a pandemic, smaller variations in antigenicity known as antigenic drift are also seen in the influenza virus (Wansbrough-Jones et al in Textbook of Medicine, 208-319, Second Edition, edited by Souhami, R.L., & Moxham, J., Churchill Livingstone (1994))..

Approximately, 6 million doses of vaccine are distributed in the UK each year. The cost of the vaccine programme in the UK exceeds £30 million yearly but this sum is small in comparison to the anticipated cost of treatment of elderly patients with the infection. Such annual vaccination programmes are also carried out in the rest of Europe and the USA and the vaccine prevents 70-80% of infections. However, the degree of protection is limited by the intense variability of the influenza virus which means that 100% protection is not possible. In particular, the outer spikes of the virus, named HA and NA, vary each year and it is these spikes which the vaccine induces immunity to in vaccinated individuals. Variation of the spike in the virus therefore negates or reduces the effect of the vaccine depending upon the amount of variation.

As an alternative to vaccination, anti-viral pharmaceutical approaches have been investigated. So far, a single antiviral drug, Amantadine (Symmetrel), has been licensed for use against influenza infections but is hardly utilised. Two new anti- neuraminidase drugs are also currently under study world-wide. Amantadine is only effective against influenza A virus and therefore cannot yet replace the use of a preventative vaccine. The drug has some benefit as a treatment of influenza infection but it does not convey 100% protection as a prophylactic, nor does it confer any protection once its use is ceased. Moreover, antiviral drugs are an expensive form of treatment.

Virucidal compounds have been described which may destroy influenza virus on contact either by dissolving the lipid surrounding the virus (Wigg et al Antivir. Chem. Chemother. 7 179-183 (1996)) or, alternatively, by binding to the protein HA spike (unpublished data). The virus is also inhibited by acid conditions. Furthermore, there are now a number of polyclonal and monoclonal antibodies which neutralise influenza virus on contact (Lambkin, R., & Dimmock, N. J., Vaccine 14 212-217 (1996)) but no therapeutic use has been made of these antibodies to date.

The influenza virus is spread predominantly via aerosol by inhalation of virus infected droplets emerging from the respiratory tract of an already infected person. A great deal of virus is excreted from the respiratory tract during the incubation period before the infected person shows clinical signs of illness. Whilst surgical masks are used in hospital, doctor's surgeries and dentist's surgeries to reduce the chance of transmission of bacteria from the surgeon or doctor to the patient or vice versa, such masks are not expected to reduce viral transmission of infectious agents because of the minute size of viruses and virus aggregates. Viruses are termed "ultrafiltrable particles" (Collier and Oxford, Human Virology, A text for students of medicine, dentistry and microbiology, OUP, (1993)) because they are able to pass through even the smallest pores of most standard filter papers or membranes. For this reason, existing barrier means, such as air filters and articles of protective clothing, in particular masks, have not been effective at preventing viral particles from reaching nasal and oral tissues.

There exists a need therefore for the provision of cheap, effective means to prevent viral infection which do not suffer from the problems of the present use of barrier means, prophylactic vaccines or therapeutic medicines none of which offer complete protection from infection.

The present invention is based in part on the realisation that the treatment of barrier materials such as paper or filters, for example air filters with virucidal or antiviral agents can provide an effective means of protecting against viral infection. It has been discovered that protection is best afforded if the barrier material contains a means for first capturing a viral particle and then secondly a means for destroying the virus. The barrier materials can also be used in the manufacture of articles of protective clothing to provide a degree of protection for the wearer, such as for example masks.

According to a first aspect of the present invention, there is provided a fibrous material which comprises a plurality of interwoven threads wherein at least one thread has been derivatised with a natural receptor for a virus or a portion or an analogue thereof.

The fibrous material may be used as a barrier material, such as for example to filter viruses from the air in a contained environment. The present invention therefore extends to a paper or fibre sheet composed from a fibrous material in accordance with the third aspect of the invention. Such papers or fibre sheets can be used as air filters which may be employed in hospitals and/or laboratory environments in which protection from airborne viral transmission is important. The filters may be utilised in masks and breathing apparatus to protect the wearer, or in working environments where viruses are being used, such as for example in filters to "scrub" air clean, or in a contained working environment to prevent escape of viruses. Alternatively, the material may be used to construct larger items such as curtains, blinds, cavity wall insulation and insulating material to block gaps around doors and windows.

The fibrous material may be used in the manufacture of articles of protective clothing, for example a mask, suitably a mask for surgical or medical procedures, an eye-patch, a head garment, a pair of long- or short-trousers, a suit, a long- or short- sleeved shirt, a skirt, a poncho, a hood, a gown, a dress or other item of clothing which can serve as a barrier between the skin of the wearer and the environment.

The fibrous material may be manufactured from any convenient material, including, cotton, wool, silk, or a polymer, or a combined multi-component fibre. Where the thread has a polymer component, the polymer may be cellulose, polyethylene (suitably, ultra-high modulus polyethylene) polyester, terylene, nylon, Lycra™, lyocell (Tencel™), or any other polymer fibre suitable for use in garment manufacture. Suitably the article can be composed of fibres of different degrees of micro fibrillation.

The degree of microfibrillation can provide the material with different filtration properties which can be readily measured by "Canadian Standard Freeness" (CSF). For example, a material exhibiting a low CSF number indicates high microfibrillation in the material and therefore a high resistance to passage of particles. The processes used to prepare fibres for use in such materials are described more fully in the official test methods and standards of the Technical Association for the Paper and Pulp Industry (TAPPI), in particular reference publication "T 200 om-89" (1989). The fibres can be prepared into the materials using Valley Beating or alternatively using "spunlace" or hydroentanglement procedures, which can be considered to consist of precursor web formation, web entanglement, water circulation, and web drying.

In the different features and aspects of the present invention, it has been seen that viral capture can be improved still further by the use of lyocell. The material may be prepared with different properties during the hydroentanglement process where the fibres are brought together. Materials composed of lyocell have been used prior to the present invention in other fields, such as for example as cigarette filters, US- A-5839,448, US-A-5738,119, US-A-5671,757.

In the different aspects of the present invention, where the article of clothing or the fibrous material is composed, or is part composed, from lyocell, the process used to prepare the lyocell may be any convenient procedure known in the art. It is preferred, however, that the lyocell be prepared with a high degree of microfibrillation. The higher the degree of Valley Beating (VB) in terms of hours leads to a lyocell material with a higher degree of microfibrillation as measured by a lower CSF value. In such processes, an identical Valley Beating time may result in slightly different CSF values. It is therefore sometimes useful to refer to the overall conditions of preparation using the CSF value as an approximate guide to the properties of the material. The time taken for Valley Beating during the preparative process may therefore provide an alternative definition of the material. However, it should also be noted that other definitions based on preparation using hydroentanglement, or alternative processes, may also be used to define materials with equivalent CSF values. The CSF value for materials useful in the present invention may be up to about 800 CSF, generally in the range of from 100-750 CSF.

In embodiments of the present invention where the lyocell is to be used as a mask or a filter in an air mask, then a high CSF value is required in order to permit the wearer to be able to breath through the mask. The CSF value may be in the range of from 600-700 CSF, suitably of from 620-680 CSF, generally of from 625-660. Particularly preferred values are 630 and 649 prepared using a Valley Beating time of about 1 hour. In embodiments of the invention where the lyocell is to be used as an air filter, a lower CSF value is required. The CSF value may be in the range of from 150-250, suitably of from 160-210, generally of from 165-180. Particularly preferred values are 173 and 175 CSF prepared using a Valley Beating time of 4 hours. Alternative definitions based on preparation using hydroentanglement may also be used to characterise materials with equivalent CSF values.

For materials prepared with a high CSF value, for example a CSF value greater than about 600, it may also be preferable to activate the fibres using a reagent such as cyanogen bromide (CNBr) to covalently bind the viral capture agent to the fibres. Such materials with high CSF values are relatively loose structurally and the viral capture agent may require firmer anchoring. In materials with more dense structures and lower CSF values, it may not be necessary to activate the fibres in this way. Without wishing to be bound by theory, it is believed that that the viral capture agent may become entangled in the mesh structure. Where an activation agent is required, the agent may be cyanogen bromide or any other suitable reagent known for this purpose.

The virus may be a DNA virus or a RNA virus. Where the virus is a DNA virus, it may comprise an envelope double-stranded, envelope single-stranded or non- enveloped double stranded. The envelope double-stranded DNA viruses include the herpes family of viruses, Varicella zoster (VZ), Herpes simplex (HSV I, II), Epstein-Barr (EBV), Cytomegalovirus (CMV), Human herpes virus 6 (HHV6), Human herpes virus 7 (HHV7), and Human herpes virus 8 (HHV8), and the pox family of viruses, Vaccinia, Variola and Orf. The envelope single-stranded DNA viruses include parvovirus and the non-enveloped double stranded DNA viruses include the adenoviruses and the papovavirus family, including papilloma and polyoma viruses. Where the virus is a RNA virus it may be envelope single- stranded, non-enveloped double stranded or non-enveloped single-stranded. Enveloped single-stranded RNA viruses include the Orthomyxovirus family (Influenza), the Paramyxovirus family (Para-influenza, Respiratory synctial, Mumps, Measles), the Togavirus family (Rubella, Alpha, Flavi), the Bunyavirus family, the Arenavirus family (Lassa, Marburg-Ebola), the Retrovirus family (HIV I, II) and the Rhabdovirus family (Rabies). The non-enveloped double-stranded RNA viruses include the Reovirus family and the non-enveloped single-stranded RNA viruses include the Picornavirus family (Rhino and Entero, including Coxsackie A, B, and Echo or Polio) (Wansbrough-Jones et al in Textbook of Medicine, 208-319, Second Edition, edited by Souhami, R.L., & Moxham, J. , Churchill Livingstone (1994)). The virus may be air-borne or in a fluid phase. If the virus is air-borne, typically it may be in an aerosol of liquid droplets. Viruses in a fluid phase may be present in any biological fluid or liquid in which a virus may survive, including water. Biological fluids include, but are not limited to sputum or an aerosol of sputum, blood, allantoic fluid, amniotic fluid, chorionic fluid, cerbrospinal fluid, synovial fluid, sweat, milk, semen, plasma. Viruses may also be present in the moisture in the exhaled breath of an infected individual or in mucous secretions of the animal body.

Animal viruses can gain entry to their host cells by binding to natural host cell viral receptors on the outer plasma membrane of the cell. The fibrous materials or articles of protective clothing made therefrom according to the present invention have at least one thread derivatised with a natural receptor for a virus or a portion or an analogue thereof. For example, the virus HIV gains entry into cells by binding to the CD4 receptor, and rhinoviruses utilise ICAM-1. In the case of the influenza virus, the virus binds to N-acetyl neuraminic acid (a sialic acid) and analogues of N- acetyl neuraminic acid. Different strains of influenza virus bind to different analogues of sialic acid. For example, avian and human influenza viruses have specificity for 2,3-gal and 2,6-gal receptors respectively. The chemistry of sialic acid is such that it can be readily coupled to polymeric substrates to provide the viral receptor on the threads of the fibrous material or an article of protective clothing made therefrom.

Alternatively, the natural receptor for a virus may be an appropriate binding agent, such as an antibody or a fragment or an analogue thereof. The antibody may be a polyclonal or a monoclonal antibody and fragments of antibodies may include the Fab, Fab', Fc, Fv, scFv among others, or a chimaeric antibody comprising portions from different animal species, e.g. mouse-human, rabbit-human, goat-human, or any functional combination thereof. The antibody, or fragment or analogue thereof, may be prepared by any convenient means known in the art, including methods using recombinant DNA technology. The binding agent may also include a lectin or lectin-based molecule. Lectin molecules with affinity for influenza viruses which could be used, include but are not limited to mannose-binding lectins such as conglutinnin which can be isolated from bovine or murine sera (also known as β- inhibitors); pulmonary surfactant protein-A (SP-A) which is a sialated C-type lectin with affinity for mannose residues; the lectin molecules known as SBA from Glycine max, DBA from Dolichos biflorus, WFA from Wisteria floribunda and VAA from Viscum album (Luther et al Archives of Virology 101 247-254 (1988)). Other lectin molecules with affinity for other viruses can also be used, such as the mannose- specific plant lectins from Cymbidium hybrid and Epipactis helleboήne and the (N- acetylglucosamine)n-specific plant lectin from Urtica dioica which are potent and selective inhibitors of human immunodeficiency virus and cytomegalo virus in vitro.

In some embodiments of the present invention, the fibrous material or article of protective clothing made therefrom may include both antibody and plasma membrane viral receptors. This may provide superior performance in trapping viral particles under certain conditions.

Different viruses may require for the preparation of differently derivatised threads and the skilled person in the art will be able to select the appropriate viral receptor (plasma membrane or antibody) for the virus to be protected against. An important requirement is that the receptor is coupled to the polymer threads in such a way that formation of filaments is not affected and the resulting filaments can then be interwoven to form a fibrous material, an article of protective clothing made from such a material, or a portion thereof. Fibrous materials or articles of protective clothing in accordance with the present invention may also comprise virucidal or antiviral compounds to destroy the captured viruses or to inhibit their activity. The virucidal compound may be any suitable compound for this use such as a disinfectant compound or a specific anti-viral compound. The disinfectant may be any substance effective to destroy the viral particle but without causing the wearer of the article of clothing any side-effects. Ethyl and isopropyl alcohol, diluted 70% with sterile water, iodine (dissolved with potassium iodide in 90% ethanol), hexachlorophene, hypochlorite solutions, phenolics, iodophores are all effective antiseptic disinfectants. The article of protective clothing may also prepared with compounds suitable to provide an acid pH in the fibres of the article which may also have an anti-viral effect. Anti-viral compounds include acyclovir, trifluridine, vidarabine, ganciclovir, zidovudine, amantadine, ribavirin and interferon-alpha. The skilled person in the art will be able to select the most appropriate agent depending upon the virus to be protected against. For example where the virus is influenza, the antiviral compound may be amantadine, often in combination with a phenolic compound. Antiviral compounds may also be used in conjunction with other virucidal compounds as appropriate.

Other compounds which may be incorporated into the fibrous material or articles of clothing made therefrom include anti-microbial agents against infectious agents such as yeasts and bacteria. Many of these compounds can be expected to have both antiviral as wells as anti-microbial activity. The skilled person in the art will be able to select the appropriate agents by reference to any standard textbook on pharmacology, for example Martindale The Extra Pharmacopoeia, 30^th edition, published by The Pharmaceutical Press, London, (1996) or Goodman and & Gilman's The Pharmacological Basis of Therapeutics , 8^th edition, McGraw-Hill, (1992). In a preferred embodiment according to the present invention, where the virus to be protected against is influenza, the sialic acid residues, other viral receptors or monoclonal or polyclonal antibodies or parts thereof or lectins will impart specificities to virus capture such that a combination of specificities can be provided in a single article of protective clothing which would capture the influenza viruses common to any particular outbreak, including avian influenza viruses of sub types HI-HI₅, along with associated viruses and/or bacteria.

In an alternative embodiment according to the present invention, the pharmaceutically active agent and the derivatised polymer thread may be woven together with un-derivatised polymer threads. This embodiment is particularly advantageous when the fibrous material is used to manufacture an article of protective clothing such as a mask and it permits the effect of the moisture of the wearer's breath to be reduced. Such moisture is likely to be absorbed into the mask as a consequence of the presence of the pharmaceutically active agent, e.g. sialic acid residues, and may tend to make the mask become damp after prolonged use.

According to a second aspect of the present invention there is provided an article of protective clothing comprising a plurality of interwoven threads wherein at least one thread is derivatised with a natural receptor for a virus, or a portion or an analogue thereof. The article of protective clothing may be as described previously, preferably a mask.

According to a third aspect of the present invention there is provided a replaceable subunit for an article of protective clothing which comprises a plurality of interwoven threads wherein at least one thread has been derivatised with a natural receptor for a virus or a portion or an analogue thereof. Where the article of clothing is a mask, the replaceable subunit may be a series of baffles. According to a fourth aspect of the present invention there is provided an air-filter which comprises a plurality of interwoven threads wherein at least one thread has been derivatised with a natural receptor for a virus, or a portion or an analogue thereof. Use of the term "air-filter" should not be interpreted as being limiting to normal air at atmospheric conditions and composition. The filters may also be used to filter other gaseous mixtures with alternative compositions.

Preferred aspects of the second and subsequent aspects of the present invention are as for the first aspect mutatis mutandis.

The present invention will now be further described by way of example with reference to the Examples which are present for the purposes of illustration only and should not be construed as being limiting on the invention. Example 1 : Virus binding bv filter materials

The ability of papers made from lyocell (Tencel™) with different degrees of microfibrillation, to filter virus from fluid was compared. The papers were prepared with different degrees of microfibrillation using different times of Valley Beating (VB). The different properties are characterised by the different CSF values. A polyclonal antiserum to Influenza A virus (National Institute for Biological Standards and Controls (NIBSC), UK) was coupled to papers using cyanogen bromide. The polyclonal antiserum was raised in sheep against haemagglutinin (HA) from an A/Sydney/5/97 (H3N2) strain of influenza virus (Retroscreen Ltd). This antiserum would be expected to capture A (H3N2) strains of virus but not A (H1N1) or influenza B virus.

Procedure for CNBr activation and conjugation of antibody (Ab) to cellulose, fibre materials, and subsequent assay Take materials and cut 6 equal size (7cm diameter) discs from each. Fill a glass dish with 150ml of a 10% CNBr solution (w/v in ddH₂0) and place all materials into solution. Incubate at 21°C for 45 minutes. Fill a glass dish with 150ml of a 0.1M NaHCO₃ buffer solution (pH 9) and place materials into solution, agitating gently. Incubate at 21°C for 5 minutes. Fill a glass dish with 150ml of ddH2O and place materials into a dish, agitating gently. Incubate at 21°C for 5 minutes. Make a 100ml volume of 1: 100 sheep anti-A/SYDNEY/5/97 pAb and place in a glass dish. Place 3 discs of each material into the pAb solution and incubate at 4°C overnight (remaining 3 discs to be negative controls). Wash materials in 150ml of a 0.1M NaHCO₃ buffer solution (pH 9) at 21°C for 5 minutes, followed by 150ml of ddH2O at 21°C for 5 minutes, with gentle agitation. Arrange materials on separate plastic funnels. Pass 1ml of neat allantoic fluid containing virus through each filter material, collect the filtrate and test by haemagglutination (HA). Pass 1ml of PBS through each filter material, collect filtrate and test by HA.

The results of three experiments are shown in the accompanying Tables 1, 2 and 3, in which different virus preparations are passed through different papers and the virus titre in the eluate is estimated. In each of Table 1 and Table 2, column 1 shows the results obtained using 1024 HA units (equivalent to 10⁸ infectious units of virus) of PIR 13, a recombinant virus with an HA antigen identical to A/SYDNEY/5/97; column 2 shows results from a lower titre unrelated influenza A virus, A/TX/36/91; and column 3 shows results from an influenza B strain B/HARBIN/7/94. Table 3 shows equivalent results, except that column 1 shows results obtained using 256 HA units of PIR 13. The appropriate virus titres are shown underneath each table. The results show that Tencel™ 175 and 503 effectively prevented virus transmission of PIR 13 whether antibody was coupled to them or not, but that Tencel™ 603 was more active when the antibody was coupled to the fibres. Similar results were also obtained with a lower titre of A/TX/36/91 and of the influenza B strain. Again the paper with the least microfibrillation let through the most virus. In each case, a "normal" unmodified cellulosic filter paper (Whatman™ No. l) had substantially less effect on virus transmission.

In Table 2, the effects of activated papers with and without antibody are compared and it can be seen that the reduction in virus titre does not appear to depend upon the activation process where the paper has a low CSF value but that for high values, such as 630 CSF the coupling procedure improves virus retention. The results in Table 2 show that activation with cyanogen bromide is not responsible for virus capture.

Table 3 shows equivalent results as for Table 1 and for Table 2, with the addition of results for the wash through of PBS. With respect to the results in Table 3, the procedure followed was as detailed above, except that 3 of the 6 discs from each material washed and placed directly into solution of polyclonal antibody (pAb) in 0.1M NaHCO₃ as unactivated controls. In Table 3, the initial virus titre is 4-fold reduced and there is no titre for A/TX/36/91 so the data relating to A/TX/36/91 in this experiment should be ignored. In preparing the Tencel™ papers for the experiments in Table 3, the same Valley Beating times were used to try to create papers with identical characteristics to those papers in Tables 1 and 2. The papers used in Table 3 have slightly different CSF values but are believed to be equivalent functionally to those in Tables 1 and 2. It can be seen in Table 3, that Tencel™ 173, like Tencel™ 175 in Tables 1 and 2, shows high resistance to flow-through, even when not activated. Additionally, Tencel™ 537 in this experiment illustrates that the activation process results in retention of all the virus whereas, when not activated the virus can be washed through readily with PBS.

Table 1

Titre of neat allantoic fluid (AF) PIR 13 - 1024 HAU

A/TX/36/91 - 128 HAU B/HARBIN/7/94 - 16 HAU

HAU - haemagglutination unit n.d. - not determined

Table 2

Titre of neat allantoic fluid (AF) PIR 13 - 1024 HAU A/TX/36/91 - 32 HAU B/HARBIN/7/94 - 16 HAU

HAU - haemagglutination unit n.d. - not determined

Table 3

Titre of neat allantoic fluid (AF) PIR 13 - 256 HAU A/TX/36/91 - < 2 HAU B/HARBIN/7/94 - 32 HAU

HAU - haemagglutination unit n.d. - not determined

Example 2: Virucidal Face Mask

A particularly preferred embodiment of the present invention is a virucidal face mask which is prepared by derivatising cellulose fibres with sialic acid residues to protect against influenza virus. The mask may be formed into the style of a medical or surgical mask.

Where the article of protective clothing is made of paper, the fibres or threads are composed of cellulose which contains hydroxy groups suitable for derivatisation with sialic acid groups which contain both hydroxy and carboxylic acid groups. It is therefore possible to couple such sialic acid groups to the cellulose polymer via iso- cyanates. The choice of di-isocyanate can be made to be appropriate for biological reasons, toxicity and to avoid any reduction in the anti-viral activity.

For a woven mesh, ultra-high modulus polyethylene fibres can be utilised. The fibres are pre-treated by ion-beam etching, or by chromic acid etching making the surface reactive. These fibres are immensely strong and very flexible for weaving. The surface of the fibre is reactive in localised spots to be the source of binding of receptors and antibodies. Alternatively, co-polymers of alpha sialoside linked to acrylamide by short connectors such as 5-acetyl-2-O-(N-acryloyl-8-amino-5- oxaoctyl)-2-6-anhydro-3,5-dideoxy-D-galacto-alpha nonulopyranosonoic acid) are utilised.

Claims

1. A fibrous material comprising a plurality of interwoven threads wherein at least one thread is derivatised with a natural receptor for a virus, or a portion or an analogue thereof.

2. A fibrous material as claimed in claim 1, in which the thread is a polymer fibre, preferably a cellulose fibre.

3. A fibrous material as claimed in claim 1 or in claim 2, in which the material has a high degree of microfibrillation as measured by Canadian Standard Freeness (CSF) of up to 800 CSF.

4. A fibrous material as claimed in any one of claims 1 to 3, in which the polymer fibre is lyocell.

5. An article of protective clothing as claimed in any one of claims 1 to 4, in which the natural receptor is a plasma membrane receptor, a lectin or an antibody.

6. A fibrous material as claimed in any one of claims 1 to 5, in which the material additionally comprises a virucidal agent or an antiviral agent.

7. A fibrous material as claimed in claim 6, in which the antiviral agent is amantadine.

8. A fibrous material as claimed in any one of claims 1 to 7, in which the material additionally comprises an anti-microbial agent.

9. A fibrous material as claimed in claim 8 in which the anti-microbial agent is a phenolic compound.

10. A fibrous material as claimed in any one of claims 1 to 9, in which the natural receptor is sialic acid or an analogue thereof.

11. An article of protective clothing comprising a plurality of interwoven threads wherein at least one thread is derivatised with a natural receptor for a virus, or a portion or an analogue thereof.

12. An article of protective clothing as claimed in claim 11, in which the article is a mask.

13. A replaceable subunit for an article of protective clothing which comprises a plurality of interwoven threads wherein at least one thread is derivatised with a natural receptor for a virus or a portion thereof.

14. A subunit as claimed in claim 13, in which the article of clothing is a mask.

15. A subunit as claimed in claim 13 or in claim 14, in which the subunit is a series of baffles.

16. An air-filter comprising a plurality of interwoven threads wherein at least one thread is derivatised with a natural receptor for a virus, or a portion or an analogue thereof.