CORD-19-Sentences  

CORD-19:d8271398b9073fbb1ad449e72697e6ae8f71d3d8 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
TextSentencer_T1 0-50 Sentence denotes Passive Broad-Spectrum Influenza Immunoprophylaxis
TextSentencer_T1 0-50 Sentence denotes Passive Broad-Spectrum Influenza Immunoprophylaxis
TextSentencer_T2 52-60 Sentence denotes Abstract
TextSentencer_T2 52-60 Sentence denotes Abstract
TextSentencer_T3 61-185 Sentence denotes Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics.
TextSentencer_T3 61-185 Sentence denotes Influenza is a perennial problem affecting millions of people annually with the everpresent threat of devastating pandemics.
TextSentencer_T4 186-310 Sentence denotes Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals.
TextSentencer_T4 186-310 Sentence denotes Active prophylaxis by vaccination against influenza virus is currently the main countermeasure supplemented with antivirals.
TextSentencer_T5 311-492 Sentence denotes However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance.
TextSentencer_T5 311-492 Sentence denotes However, disadvantages of this strategy include the impact of antigenic drift, necessitating constant updating of vaccine strain composition, and emerging antiviral drug resistance.
TextSentencer_T6 493-735 Sentence denotes The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest.
TextSentencer_T6 493-735 Sentence denotes The development of other options for influenza prophylaxis, particularly with broad acting agents able to provide protection in the period between the onset of a pandemic and the development of a strain specific vaccine, is of great interest.
TextSentencer_T7 736-869 Sentence denotes Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks.
TextSentencer_T7 736-869 Sentence denotes Exploitation of broad-spectrum mediators could provide barricade protection in the early critical phase of influenza virus outbreaks.
TextSentencer_T8 870-1094 Sentence denotes Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic.
TextSentencer_T8 870-1094 Sentence denotes Passive immunity has the potential to provide immediate antiviral effects, inhibiting virus replication, reducing virus shedding, and thereby protecting vulnerable populations in the event of an impending influenza pandemic.
TextSentencer_T9 1095-1251 Sentence denotes Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.
TextSentencer_T9 1095-1251 Sentence denotes Here, we review passive broad-spectrum influenza prophylaxis options with a focus on harnessing natural host defenses, including interferons and antibodies.
TextSentencer_T10 1253-1461 Sentence denotes Seasonal influenza causes serious disease burden, particularly in children and the elderly, with the need to develop annual vaccines based on predicted circulating strains due to antigenic drift of the virus.
TextSentencer_T10 1253-1461 Sentence denotes Seasonal influenza causes serious disease burden, particularly in children and the elderly, with the need to develop annual vaccines based on predicted circulating strains due to antigenic drift of the virus.
TextSentencer_T11 1462-1603 Sentence denotes Furthermore, newly emerging novel influenza A viruses pose a significant threat of a pandemic with potentially devastating consequences [1] .
TextSentencer_T11 1462-1603 Sentence denotes Furthermore, newly emerging novel influenza A viruses pose a significant threat of a pandemic with potentially devastating consequences [1] .
TextSentencer_T12 1604-1779 Sentence denotes Moreover, as pandemic strain vaccines require time for development and deployment, virus replication and spread are initially unchecked allowing the outbreak to gain momentum.
TextSentencer_T12 1604-1779 Sentence denotes Moreover, as pandemic strain vaccines require time for development and deployment, virus replication and spread are initially unchecked allowing the outbreak to gain momentum.
TextSentencer_T13 1780-1918 Sentence denotes Currently, vaccines and antivirals are used for control of influenza but emerging virus resistance to these measures presents limitations.
TextSentencer_T13 1780-1918 Sentence denotes Currently, vaccines and antivirals are used for control of influenza but emerging virus resistance to these measures presents limitations.
TextSentencer_T14 1919-2076 Sentence denotes Furthermore, as antiviral drugs could not be stockpiled in sufficient amounts for global supply, alternative control measures need to be urgently considered.
TextSentencer_T14 1919-2076 Sentence denotes Furthermore, as antiviral drugs could not be stockpiled in sufficient amounts for global supply, alternative control measures need to be urgently considered.
TextSentencer_T15 2077-2314 Sentence denotes A potential solution lies in the development of a universal vaccine based on conserved viral epitopes that induces cross-reactive antibodies that neutralize variant viruses from within a subtype and protects against heterologous viruses.
TextSentencer_T15 2077-2314 Sentence denotes A potential solution lies in the development of a universal vaccine based on conserved viral epitopes that induces cross-reactive antibodies that neutralize variant viruses from within a subtype and protects against heterologous viruses.
TextSentencer_T16 2315-2641 Sentence denotes Therefore, whilst existing vaccines are inadequate for cross protection and a universal vaccine may be difficult to achieve, it is both pertinent and timely to consider other possible broadspectrum options, particularly as different virus subtypes not previously experienced by humans are emerging and have pandemic potential.
TextSentencer_T16 2315-2641 Sentence denotes Therefore, whilst existing vaccines are inadequate for cross protection and a universal vaccine may be difficult to achieve, it is both pertinent and timely to consider other possible broadspectrum options, particularly as different virus subtypes not previously experienced by humans are emerging and have pandemic potential.
TextSentencer_T17 2642-2785 Sentence denotes In this review, we discuss broadspectrum control options with emphasis on harnessing the power of natural immunity via neutralizing antibodies.
TextSentencer_T17 2642-2785 Sentence denotes In this review, we discuss broadspectrum control options with emphasis on harnessing the power of natural immunity via neutralizing antibodies.
TextSentencer_T18 2786-3009 Sentence denotes Effective passive broad-spectrum protection during the early phase of an epidemic could provide a barricade to virus exposure, especially during the interval between virus identification and active vaccine-induced immunity.
TextSentencer_T18 2786-3009 Sentence denotes Effective passive broad-spectrum protection during the early phase of an epidemic could provide a barricade to virus exposure, especially during the interval between virus identification and active vaccine-induced immunity.
TextSentencer_T19 3010-3190 Sentence denotes As a consequence, early intervention with passive prophylaxis may revolutionize control options for influenza with potential impact on seasonal and pandemic influenza preparedness.
TextSentencer_T19 3010-3190 Sentence denotes As a consequence, early intervention with passive prophylaxis may revolutionize control options for influenza with potential impact on seasonal and pandemic influenza preparedness.
TextSentencer_T20 3191-3350 Sentence denotes Influenza A (H1N1 and H3N2) and influenza B viruses cause seasonal disease in the winter months of both hemispheres with 250,000-500,000 deaths each year [2] .
TextSentencer_T20 3191-3350 Sentence denotes Influenza A (H1N1 and H3N2) and influenza B viruses cause seasonal disease in the winter months of both hemispheres with 250,000-500,000 deaths each year [2] .
TextSentencer_T21 3351-3856 Sentence denotes Although the natural animal reservoir for influenza A viruses is aquatic shorebirds, high pathogenicity avian influenza (HPAI) viruses 2 Influenza Research and Treatment have recently emerged with high fatality rates in domestic poultry and species cross over into humans, with HA dual binding affinities for 2,3-linked and 2,6-linked sialic acid receptors, predominantly found in avian species and humans, respectively [3] , allowing increased infectivity of avian viruses in the human respiratory tract.
TextSentencer_T21 3351-3856 Sentence denotes Although the natural animal reservoir for influenza A viruses is aquatic shorebirds, high pathogenicity avian influenza (HPAI) viruses 2 Influenza Research and Treatment have recently emerged with high fatality rates in domestic poultry and species cross over into humans, with HA dual binding affinities for 2,3-linked and 2,6-linked sialic acid receptors, predominantly found in avian species and humans, respectively [3] , allowing increased infectivity of avian viruses in the human respiratory tract.
TextSentencer_T22 3857-4042 Sentence denotes Mortality rates for HPAI H5N1 spreading throughout Eurasia and the newly emerged H7N9 virus in China are around 60% and 30%, respectively, for reported human cases of infection [4, 5] .
TextSentencer_T22 3857-4042 Sentence denotes Mortality rates for HPAI H5N1 spreading throughout Eurasia and the newly emerged H7N9 virus in China are around 60% and 30%, respectively, for reported human cases of infection [4, 5] .
TextSentencer_T23 4043-4128 Sentence denotes At the present time, human-to-human transmission of these viruses is relatively rare.
TextSentencer_T23 4043-4128 Sentence denotes At the present time, human-to-human transmission of these viruses is relatively rare.
TextSentencer_T24 4129-4413 Sentence denotes Confounding factors for avian influenza virus vaccine development include genetic engineering of the virus for better growth in eggs, poorer immunogenicity than seasonal influenza H1 and H3 subtypes in humans, and the need for use of higher doses and/or adjuvants to improve efficacy.
TextSentencer_T24 4129-4413 Sentence denotes Confounding factors for avian influenza virus vaccine development include genetic engineering of the virus for better growth in eggs, poorer immunogenicity than seasonal influenza H1 and H3 subtypes in humans, and the need for use of higher doses and/or adjuvants to improve efficacy.
TextSentencer_T25 4414-4587 Sentence denotes Four pandemics have occurred since the start of the 20th century, the most severe occurring in 1918 due to the Spanish flu pandemic with an estimated 50 million deaths [6] .
TextSentencer_T25 4414-4587 Sentence denotes Four pandemics have occurred since the start of the 20th century, the most severe occurring in 1918 due to the Spanish flu pandemic with an estimated 50 million deaths [6] .
TextSentencer_T26 4588-4806 Sentence denotes Recently, novel H1N1 viruses emerged causing a pandemic in 2009 due to a natural reassortant swine influenza A virus, which was different to the H1N1 virus that had been cocirculating with H3N2 viruses since 1977 [7] .
TextSentencer_T26 4588-4806 Sentence denotes Recently, novel H1N1 viruses emerged causing a pandemic in 2009 due to a natural reassortant swine influenza A virus, which was different to the H1N1 virus that had been cocirculating with H3N2 viruses since 1977 [7] .
TextSentencer_T27 4807-5169 Sentence denotes Reassortant viruses have been constructed in the laboratory to investigate their transmission and virulence, with one virus possessing the H5 HA gene derived from a HPAI H5N1 virus combined with the remaining seven gene segments from a 2009 H1N1 pandemic virus, displaying greater virulence than HPAI H5N1 with potential of increased mammalian transmission [8] .
TextSentencer_T27 4807-5169 Sentence denotes Reassortant viruses have been constructed in the laboratory to investigate their transmission and virulence, with one virus possessing the H5 HA gene derived from a HPAI H5N1 virus combined with the remaining seven gene segments from a 2009 H1N1 pandemic virus, displaying greater virulence than HPAI H5N1 with potential of increased mammalian transmission [8] .
TextSentencer_T28 5170-5327 Sentence denotes Thus we cannot be complacent with the continued threat of a pandemic by such new emerging pathogenic influenza viruses with increased mammalian transmission.
TextSentencer_T28 5170-5327 Sentence denotes Thus we cannot be complacent with the continued threat of a pandemic by such new emerging pathogenic influenza viruses with increased mammalian transmission.
TextSentencer_T29 5328-5507 Sentence denotes As influenza virus replication also impairs the mucociliary clearance, there is increased susceptibility to bacterial superinfections, which can often be fatal (reviewed in [9] ).
TextSentencer_T29 5328-5507 Sentence denotes As influenza virus replication also impairs the mucociliary clearance, there is increased susceptibility to bacterial superinfections, which can often be fatal (reviewed in [9] ).
TextSentencer_T30 5508-5741 Sentence denotes In addition, immune dysfunction in those prone to respiratory disease with excessive cytokine stimulation in the airways during influenza virus infection can rapidly progress to pneumonia with fatal acute lung injury [10] [11] [12] .
TextSentencer_T30 5508-5741 Sentence denotes In addition, immune dysfunction in those prone to respiratory disease with excessive cytokine stimulation in the airways during influenza virus infection can rapidly progress to pneumonia with fatal acute lung injury [10] [11] [12] .
TextSentencer_T31 5742-6029 Sentence denotes Thus effective strategies to combat influenza pandemics of catastrophic proportions involve both the generation of broad-spectrum immunity and protection from immunopathology, thereby lowering the risk of severe illness-associated complications and reducing both morbidity and mortality.
TextSentencer_T31 5742-6029 Sentence denotes Thus effective strategies to combat influenza pandemics of catastrophic proportions involve both the generation of broad-spectrum immunity and protection from immunopathology, thereby lowering the risk of severe illness-associated complications and reducing both morbidity and mortality.
TextSentencer_T32 6030-6087 Sentence denotes Current influenza control requires effective vaccination.
TextSentencer_T32 6030-6087 Sentence denotes Current influenza control requires effective vaccination.
TextSentencer_T33 6088-6293 Sentence denotes Updated vaccines with strain matching are developed on an annual basis requiring seed virus preparation generated by either reassortment or reverse genetics for propagation in eggs or cultured cells [13] .
TextSentencer_T33 6088-6293 Sentence denotes Updated vaccines with strain matching are developed on an annual basis requiring seed virus preparation generated by either reassortment or reverse genetics for propagation in eggs or cultured cells [13] .
TextSentencer_T34 6294-6533 Sentence denotes Recombinant DNA plasmidbased and virus-like particle vaccines are alternative options [14] to currently licensed inactivated and live attenuated vaccines (cold-adapted and temperature-sensitive viruses) [15] and recombinant proteins [16] .
TextSentencer_T34 6294-6533 Sentence denotes Recombinant DNA plasmidbased and virus-like particle vaccines are alternative options [14] to currently licensed inactivated and live attenuated vaccines (cold-adapted and temperature-sensitive viruses) [15] and recombinant proteins [16] .
TextSentencer_T35 6534-6707 Sentence denotes Heterosubtypic immunity is conferred by a variety of experimental vaccines including extracellular domain matrix (M2) protein [17] and formalininactivated whole virus [18] .
TextSentencer_T35 6534-6707 Sentence denotes Heterosubtypic immunity is conferred by a variety of experimental vaccines including extracellular domain matrix (M2) protein [17] and formalininactivated whole virus [18] .
TextSentencer_T36 6708-6885 Sentence denotes Nonetheless, such contemporary vaccines would have narrow virus specificity, delayed availability, and restricted capacity to meet the global demand during a pandemic situation.
TextSentencer_T36 6708-6885 Sentence denotes Nonetheless, such contemporary vaccines would have narrow virus specificity, delayed availability, and restricted capacity to meet the global demand during a pandemic situation.
TextSentencer_T37 6886-7159 Sentence denotes Universal influenza vaccines that target invariant regions of the virus and induce effective broadly neutralizing immune responses could potentially provide more effective antiviral coverage but finding an appropriate immunogen is a major issue under intense investigation.
TextSentencer_T37 6886-7159 Sentence denotes Universal influenza vaccines that target invariant regions of the virus and induce effective broadly neutralizing immune responses could potentially provide more effective antiviral coverage but finding an appropriate immunogen is a major issue under intense investigation.
TextSentencer_T38 7160-7348 Sentence denotes A further limitation is efficacy as vaccine-induced B cell responses to conserved regions of the HA viral protein are generally low in frequency and generate poor antibody responses [19] .
TextSentencer_T38 7160-7348 Sentence denotes A further limitation is efficacy as vaccine-induced B cell responses to conserved regions of the HA viral protein are generally low in frequency and generate poor antibody responses [19] .
TextSentencer_T39 7349-7622 Sentence denotes Neuraminidase inhibitors, although potent at inactivating virus replication, have been shown to display limited effectiveness when used beyond 48 hours after infection due to high viral titres and require regular dosing to those at risk of exposure during a virus outbreak.
TextSentencer_T39 7349-7622 Sentence denotes Neuraminidase inhibitors, although potent at inactivating virus replication, have been shown to display limited effectiveness when used beyond 48 hours after infection due to high viral titres and require regular dosing to those at risk of exposure during a virus outbreak.
TextSentencer_T40 7623-7910 Sentence denotes Other antivirals besides NA inhibitors (zanamivir and oseltamivir) that block the M2ion channel (adamantanes) have been used; however prepandemic stockpiling of such antivirals by governments has been reconsidered as a poor strategy against emerging virus resistance (reviewed in [20] ).
TextSentencer_T40 7623-7910 Sentence denotes Other antivirals besides NA inhibitors (zanamivir and oseltamivir) that block the M2ion channel (adamantanes) have been used; however prepandemic stockpiling of such antivirals by governments has been reconsidered as a poor strategy against emerging virus resistance (reviewed in [20] ).
TextSentencer_T41 7911-8217 Sentence denotes Antiviral development has targeted specific oligosaccharide-comprised sites on enveloped viruses (cyanovirin) [21] , viral RNA dependent RNA polymerase (favipiravir) [22] , and their possible combination targeting different stages of the virus replication cycle in a synergistic therapeutic approach [23] .
TextSentencer_T41 7911-8217 Sentence denotes Antiviral development has targeted specific oligosaccharide-comprised sites on enveloped viruses (cyanovirin) [21] , viral RNA dependent RNA polymerase (favipiravir) [22] , and their possible combination targeting different stages of the virus replication cycle in a synergistic therapeutic approach [23] .
TextSentencer_T42 8218-8676 Sentence denotes Innovative drugs may offer future clinical benefits including (DAS181) that mediates cleavage of sialic acid from host glycan receptors [24] ,defensins and antiviral peptides that prevent virion entry [25] , TLR3 ligand (PIKA) promotion of DC maturation [26] , TLR4 antagonists (eritoran) that block cytokine cascades [27] , nucleic acid-based drug (PolyIC, CpG) activation of innate immunity [28] , and siRNA that target conserved viral RNA sequences [29] .
TextSentencer_T42 8218-8676 Sentence denotes Innovative drugs may offer future clinical benefits including (DAS181) that mediates cleavage of sialic acid from host glycan receptors [24] ,defensins and antiviral peptides that prevent virion entry [25] , TLR3 ligand (PIKA) promotion of DC maturation [26] , TLR4 antagonists (eritoran) that block cytokine cascades [27] , nucleic acid-based drug (PolyIC, CpG) activation of innate immunity [28] , and siRNA that target conserved viral RNA sequences [29] .
TextSentencer_T43 8677-8905 Sentence denotes Furthermore, enveloped virus neutralizing compounds (polyphenols) found in pomegranate juice [30] and green tea [31] and even scorpion venom peptide [32] hold promise in their strain diversity-independence of antiviral activity.
TextSentencer_T43 8677-8905 Sentence denotes Furthermore, enveloped virus neutralizing compounds (polyphenols) found in pomegranate juice [30] and green tea [31] and even scorpion venom peptide [32] hold promise in their strain diversity-independence of antiviral activity.
TextSentencer_T44 8906-9092 Sentence denotes Innate IFNs are potent pleiotropic cytokines that can stimulate cells to induce an antiviral state through signal transduction pathways activating transcription of specific gene subsets.
TextSentencer_T44 8906-9092 Sentence denotes Innate IFNs are potent pleiotropic cytokines that can stimulate cells to induce an antiviral state through signal transduction pathways activating transcription of specific gene subsets.
TextSentencer_T45 9093-9342 Sentence denotes The IFN molecules comprise multiple subtype proteins belonging to the types I, II, and III families and play important roles in early host defense against virus infections through their diverse antiviral and immunomodulatory properties ( Figure 1 ).
TextSentencer_T45 9093-9342 Sentence denotes The IFN molecules comprise multiple subtype proteins belonging to the types I, II, and III families and play important roles in early host defense against virus infections through their diverse antiviral and immunomodulatory properties ( Figure 1 ).
TextSentencer_T46 9343-9486 Sentence denotes IFN-/ are the best characterized of the type I IFN family, which is comprised of IFN-(1-14 subtypes), beta, tau, epsilon, omega, and many more.
TextSentencer_T46 9343-9486 Sentence denotes IFN-/ are the best characterized of the type I IFN family, which is comprised of IFN-(1-14 subtypes), beta, tau, epsilon, omega, and many more.
TextSentencer_T47 9487-9718 Sentence denotes However, influenza viruses can evade innate immunity in part through the nonstructural-(NS-) 1 protein, targeting interferon regulatory factor-(IRF-) 3, blocking IFN promoter activity and antagonizing endogenous IFN pathways [40] .
TextSentencer_T47 9487-9718 Sentence denotes However, influenza viruses can evade innate immunity in part through the nonstructural-(NS-) 1 protein, targeting interferon regulatory factor-(IRF-) 3, blocking IFN promoter activity and antagonizing endogenous IFN pathways [40] .
TextSentencer_T48 9719-9877 Sentence denotes Type I IFN subtypes: IFN-, IFN-, IFN-, IFN-, IFNs [41] or IFN-inducible proteins (viperin) [42] provide broad-spectrum protection against influenza A viruses.
TextSentencer_T48 9719-9877 Sentence denotes Type I IFN subtypes: IFN-, IFN-, IFN-, IFN-, IFNs [41] or IFN-inducible proteins (viperin) [42] provide broad-spectrum protection against influenza A viruses.
TextSentencer_T49 9878-10039 Sentence denotes The IFNs have been shown to activate transcription of about 2,000 IFN-stimulated genes (ISG) [33] with heterogeneous antiviral activity in mammalian cells [34] .
TextSentencer_T49 9878-10039 Sentence denotes The IFNs have been shown to activate transcription of about 2,000 IFN-stimulated genes (ISG) [33] with heterogeneous antiviral activity in mammalian cells [34] .
TextSentencer_T50 10040-10252 Sentence denotes Major antiviral states are induced by RNaseL, inhibiting viral nucleic acid replication [35] , 2-5OAS, blocking virus protein translation [36] , and Mx, abrogating the formation of viral ribonucleoproteins [37] .
TextSentencer_T50 10040-10252 Sentence denotes Major antiviral states are induced by RNaseL, inhibiting viral nucleic acid replication [35] , 2-5OAS, blocking virus protein translation [36] , and Mx, abrogating the formation of viral ribonucleoproteins [37] .
TextSentencer_T51 10253-10354 Sentence denotes IFNs can also affect immune cell proliferation, differentiation, maturation, migration, and survival.
TextSentencer_T51 10253-10354 Sentence denotes IFNs can also affect immune cell proliferation, differentiation, maturation, migration, and survival.
TextSentencer_T52 10355-10548 Sentence denotes IFNs orchestrate the downstream adaptive immune responses by activating B cells to switch antibody class secretion and by stimulating T cell proliferation and survival to sustain T cell memory.
TextSentencer_T52 10355-10548 Sentence denotes IFNs orchestrate the downstream adaptive immune responses by activating B cells to switch antibody class secretion and by stimulating T cell proliferation and survival to sustain T cell memory.
TextSentencer_T53 10549-10793 Sentence denotes Although each protein of the type I IFN family binds a single type of cell surface receptor (IFNAR), the binding affinities and downstream signaling pathways differ resulting in activation of ISG subsets influenced by virus and cell type [38] .
TextSentencer_T53 10549-10793 Sentence denotes Although each protein of the type I IFN family binds a single type of cell surface receptor (IFNAR), the binding affinities and downstream signaling pathways differ resulting in activation of ISG subsets influenced by virus and cell type [38] .
TextSentencer_T54 10794-10875 Sentence denotes IFNs have been used for clinical therapy of a variety of infections and diseases.
TextSentencer_T54 10794-10875 Sentence denotes IFNs have been used for clinical therapy of a variety of infections and diseases.
TextSentencer_T55 10876-11016 Sentence denotes Although IFN therapy predominantly utilizes IFN-2, other subtypes may be more or less effective, depending on the virus and cell type [39] .
TextSentencer_T55 10876-11016 Sentence denotes Although IFN therapy predominantly utilizes IFN-2, other subtypes may be more or less effective, depending on the virus and cell type [39] .
TextSentencer_T56 11017-11228 Sentence denotes Differential efficacies have been found for individual IFN subtypes in mouse models of influenza, with IFN-5 and IFN-6 subtypes being more effective than IFN-1 in reducing lung H1N1 influenza virus titers [43] .
TextSentencer_T56 11017-11228 Sentence denotes Differential efficacies have been found for individual IFN subtypes in mouse models of influenza, with IFN-5 and IFN-6 subtypes being more effective than IFN-1 in reducing lung H1N1 influenza virus titers [43] .
TextSentencer_T57 11229-11435 Sentence denotes The IFN-subtype has also been shown to protect against H1N1, driving a pulmonary Th1 type response beyond day 8, which normally switches to Th2 with eosinophilia/neutrophilia during natural infection [44] .
TextSentencer_T57 11229-11435 Sentence denotes The IFN-subtype has also been shown to protect against H1N1, driving a pulmonary Th1 type response beyond day 8, which normally switches to Th2 with eosinophilia/neutrophilia during natural infection [44] .
TextSentencer_T58 11436-11596 Sentence denotes IFN delivery has often been via bolus injections, which can have adverse side effects including severe influenza-like illness with fatigue and depression [45] .
TextSentencer_T58 11436-11596 Sentence denotes IFN delivery has often been via bolus injections, which can have adverse side effects including severe influenza-like illness with fatigue and depression [45] .
TextSentencer_T59 11597-11814 Sentence denotes Intranasal instillations of IFN to the respiratory mucosa can protect susceptible type II alveolar epithelial cells from influenza virus infection but is associated with various efficacies in preclinical trials [46] .
TextSentencer_T59 11597-11814 Sentence denotes Intranasal instillations of IFN to the respiratory mucosa can protect susceptible type II alveolar epithelial cells from influenza virus infection but is associated with various efficacies in preclinical trials [46] .
TextSentencer_T60 11815-11980 Sentence denotes Questions that still need to be adequately addressed are the timing, route, and dosage of IFN regimens for effective cover as a protective measure against influenza.
TextSentencer_T60 11815-11980 Sentence denotes Questions that still need to be adequately addressed are the timing, route, and dosage of IFN regimens for effective cover as a protective measure against influenza.
TextSentencer_T61 11981-12120 Sentence denotes Importantly, exogenous IFN cannot be immunogenic; otherwise neutralizing antibody responses develop, rendering treatment ineffective [47] .
TextSentencer_T61 11981-12120 Sentence denotes Importantly, exogenous IFN cannot be immunogenic; otherwise neutralizing antibody responses develop, rendering treatment ineffective [47] .
TextSentencer_T62 12121-12421 Sentence denotes In an attempt to overcome adverse side effects with current modes of IFN-treatment, a recent clinical trial investigating administration of low-dose oral IFNprophylaxis was undertaken but was deemed ineffective in protection against acute respiratory illness during the 2009 influenza pandemic [48] .
TextSentencer_T62 12121-12421 Sentence denotes In an attempt to overcome adverse side effects with current modes of IFN-treatment, a recent clinical trial investigating administration of low-dose oral IFNprophylaxis was undertaken but was deemed ineffective in protection against acute respiratory illness during the 2009 influenza pandemic [48] .
TextSentencer_T63 12422-12657 Sentence denotes More recently, the type III IFN-lambda family was discovered ( -1-3) and found to induce similar antiviral effects to the type I IFNs except for their cell-restriction and signaling mainly in epithelial cells and hepatocytes [49, 50] .
TextSentencer_T63 12422-12657 Sentence denotes More recently, the type III IFN-lambda family was discovered ( -1-3) and found to induce similar antiviral effects to the type I IFNs except for their cell-restriction and signaling mainly in epithelial cells and hepatocytes [49, 50] .
TextSentencer_T64 12658-12869 Sentence denotes Although these IL-10-like cytokines bind receptors distinct to the type I IFNs, most cells in the body can produce both IFN types, which are induced by TLR activation and internal sensors such as RIG-I and MDA5.
TextSentencer_T64 12658-12869 Sentence denotes Although these IL-10-like cytokines bind receptors distinct to the type I IFNs, most cells in the body can produce both IFN types, which are induced by TLR activation and internal sensors such as RIG-I and MDA5.
TextSentencer_T65 12870-13022 Sentence denotes Both IFN-/ and IFN-have been shown to be important for control of influenza in experimental animal models utilizing double receptor knockout mice [51] .
TextSentencer_T65 12870-13022 Sentence denotes Both IFN-/ and IFN-have been shown to be important for control of influenza in experimental animal models utilizing double receptor knockout mice [51] .
TextSentencer_T66 13023-13208 Sentence denotes Paradoxically, IFNs may either reduce or enhance inflammatory conditions [52] , and as such their repeated applications to the respiratory tract need to be addressed in clinical trials.
TextSentencer_T66 13023-13208 Sentence denotes Paradoxically, IFNs may either reduce or enhance inflammatory conditions [52] , and as such their repeated applications to the respiratory tract need to be addressed in clinical trials.
TextSentencer_T67 13209-13312 Sentence denotes Importantly, unregulated IFN protein levels can exacerbate lung inflammation and immunopathology [53] .
TextSentencer_T67 13209-13312 Sentence denotes Importantly, unregulated IFN protein levels can exacerbate lung inflammation and immunopathology [53] .
TextSentencer_T68 13313-13491 Sentence denotes Regulation of IFN pathways is complex, mediated by receptor density, binding affinity, STAT phosphorylation and multimerization, ISG transcription, and regulatory feedback loops.
TextSentencer_T68 13313-13491 Sentence denotes Regulation of IFN pathways is complex, mediated by receptor density, binding affinity, STAT phosphorylation and multimerization, ISG transcription, and regulatory feedback loops.
TextSentencer_T69 13492-13714 Sentence denotes Unless an improved safety regime is utilized, clinical studies using type I and type III IFN appear to show limited potential for influenza prophylaxis and are unsuitable for long-term protection of the respiratory mucosa.
TextSentencer_T69 13492-13714 Sentence denotes Unless an improved safety regime is utilized, clinical studies using type I and type III IFN appear to show limited potential for influenza prophylaxis and are unsuitable for long-term protection of the respiratory mucosa.
TextSentencer_T70 13715-13854 Sentence denotes Further limitations of exogenous IFN production capacity and species-specificity of IFN signaling may be disadvantages in pandemic control.
TextSentencer_T70 13715-13854 Sentence denotes Further limitations of exogenous IFN production capacity and species-specificity of IFN signaling may be disadvantages in pandemic control.
TextSentencer_T71 13855-14027 Sentence denotes Stimulation of polyclonal B cells can generate circulating antibody pools with multiple epitope reactivity induced by vaccination or natural infection with influenza virus.
TextSentencer_T71 13855-14027 Sentence denotes Stimulation of polyclonal B cells can generate circulating antibody pools with multiple epitope reactivity induced by vaccination or natural infection with influenza virus.
TextSentencer_T72 14028-14161 Sentence denotes Antibodies blocking the binding of viral HA proteins to cell surface receptors directly neutralize the virus and prevent virus entry.
TextSentencer_T72 14028-14161 Sentence denotes Antibodies blocking the binding of viral HA proteins to cell surface receptors directly neutralize the virus and prevent virus entry.
TextSentencer_T73 14162-14455 Sentence denotes Once the virus infection cycle has been abrogated by such humoral immune responses, the spread of virus to neighboring cells is inhibited, virus shedding is reduced, and the infection cleared through a combined antibody and effector T cell response [54] , extensively reviewed elsewhere [55] .
TextSentencer_T73 14162-14455 Sentence denotes Once the virus infection cycle has been abrogated by such humoral immune responses, the spread of virus to neighboring cells is inhibited, virus shedding is reduced, and the infection cleared through a combined antibody and effector T cell response [54] , extensively reviewed elsewhere [55] .
TextSentencer_T74 14456-14650 Sentence denotes Importantly, the production of highly functional neutralizing antibodies against HA epitopes of influenza viruses, even at nominal levels, is a relative correlate of protection [56] (Figure 2 ).
TextSentencer_T74 14456-14650 Sentence denotes Importantly, the production of highly functional neutralizing antibodies against HA epitopes of influenza viruses, even at nominal levels, is a relative correlate of protection [56] (Figure 2 ).
TextSentencer_T75 14651-14781 Sentence denotes Cognate signals and secreted factors from activated CD4 + T helper cells also activate B cells to secrete virus-specific antibody.
TextSentencer_T75 14651-14781 Sentence denotes Cognate signals and secreted factors from activated CD4 + T helper cells also activate B cells to secrete virus-specific antibody.
TextSentencer_T76 14782-15068 Sentence denotes Extrafollicular antibodysecreting cells that mainly produce early IgM are regulated by type I IFN and IL-12 cytokines, whereas inherent innate host factors influence mature B cells through a process of class switching to produce IgG during the course of influenza virus infection [57] .
TextSentencer_T76 14782-15068 Sentence denotes Extrafollicular antibodysecreting cells that mainly produce early IgM are regulated by type I IFN and IL-12 cytokines, whereas inherent innate host factors influence mature B cells through a process of class switching to produce IgG during the course of influenza virus infection [57] .
TextSentencer_T77 15069-15232 Sentence denotes Memory B cells and antibody-secreting cells formed in germinal centers can produce virus-specific antibody in a recall response to secondary virus infection [58] .
TextSentencer_T77 15069-15232 Sentence denotes Memory B cells and antibody-secreting cells formed in germinal centers can produce virus-specific antibody in a recall response to secondary virus infection [58] .
TextSentencer_T78 15233-15461 Sentence denotes Trivalent inactivated and live attenuated vaccines predominantly induce humoral responses with neutralizing antibodies directed against the HA globular head domain, which block specific virus binding thus inhibiting virus entry.
TextSentencer_T78 15233-15461 Sentence denotes Trivalent inactivated and live attenuated vaccines predominantly induce humoral responses with neutralizing antibodies directed against the HA globular head domain, which block specific virus binding thus inhibiting virus entry.
TextSentencer_T79 15462-15611 Sentence denotes However, such antibody specificities can be limited in efficacy against variable viral sequences due to the high mutation rate in the HA head domain.
TextSentencer_T79 15462-15611 Sentence denotes However, such antibody specificities can be limited in efficacy against variable viral sequences due to the high mutation rate in the HA head domain.
TextSentencer_T80 15612-15759 Sentence denotes Currently, there is renewed interest in passive immunity mediated by neutralizing antibodies for protection against influenza [59] [60] [61] [62] .
TextSentencer_T80 15612-15759 Sentence denotes Currently, there is renewed interest in passive immunity mediated by neutralizing antibodies for protection against influenza [59] [60] [61] [62] .
TextSentencer_T81 15760-16015 Sentence denotes Convalescent sera from survivors of the H1N1 Spanish Flu pandemic were reported to reduce mortality rates [63] and convalescent plasma treatment was deemed effective for H5N1-infected individuals in China [64] and for the pandemic H1N1 in Hong Kong [65] .
TextSentencer_T81 15760-16015 Sentence denotes Convalescent sera from survivors of the H1N1 Spanish Flu pandemic were reported to reduce mortality rates [63] and convalescent plasma treatment was deemed effective for H5N1-infected individuals in China [64] and for the pandemic H1N1 in Hong Kong [65] .
TextSentencer_T82 16016-16253 Sentence denotes It is noteworthy that even a relatively low titre of anti-HA antibody in convalescent plasma (HAI titer 128) protected 100% ferrets from a fatal HPAI H5N1 virus infection, when passively transferred 24 hours before virus challenge [66] .
TextSentencer_T82 16016-16253 Sentence denotes It is noteworthy that even a relatively low titre of anti-HA antibody in convalescent plasma (HAI titer 128) protected 100% ferrets from a fatal HPAI H5N1 virus infection, when passively transferred 24 hours before virus challenge [66] .
TextSentencer_T83 16254-16493 Sentence denotes Intranasal delivery of bovine IgG obtained from colostrum was found to provide passive prophylaxis for Influenza Research and Treatment 5 influenza in mice, when both specificity of antibodies and challenge virus were strain-matched [67] .
TextSentencer_T83 16254-16493 Sentence denotes Intranasal delivery of bovine IgG obtained from colostrum was found to provide passive prophylaxis for Influenza Research and Treatment 5 influenza in mice, when both specificity of antibodies and challenge virus were strain-matched [67] .
TextSentencer_T84 16494-16661 Sentence denotes Broader efficacy of antibodies with neutralizing capacity may be achievable with a mixture of polyclonal antibody specificities raised against multivalent HA vaccines.
TextSentencer_T84 16494-16661 Sentence denotes Broader efficacy of antibodies with neutralizing capacity may be achievable with a mixture of polyclonal antibody specificities raised against multivalent HA vaccines.
TextSentencer_T85 16662-16909 Sentence denotes Alternatively, broadly neutralizing antibodies to conserved regions of the HA capable of neutralizing different strains within a subtype and group or between groups and types of influenza viruses may be effective as a prophylactic interim therapy.
TextSentencer_T85 16662-16909 Sentence denotes Alternatively, broadly neutralizing antibodies to conserved regions of the HA capable of neutralizing different strains within a subtype and group or between groups and types of influenza viruses may be effective as a prophylactic interim therapy.
TextSentencer_T86 16910-17125 Sentence denotes In addition to antihead HA antibodies, some antistalk HA antibodies have been shown to block fusion [68] and promote antibody-dependent cellular cytotoxicity of infected cells with broad neutralizing capacity [69] .
TextSentencer_T86 16910-17125 Sentence denotes In addition to antihead HA antibodies, some antistalk HA antibodies have been shown to block fusion [68] and promote antibody-dependent cellular cytotoxicity of infected cells with broad neutralizing capacity [69] .
TextSentencer_T87 17126-17313 Sentence denotes As routine haemagglutination inhibition assays do not detect antistalk antibodies, the discovery and potential of HA-stalkspecific antibodies largely remained unknown for some time [70] .
TextSentencer_T87 17126-17313 Sentence denotes As routine haemagglutination inhibition assays do not detect antistalk antibodies, the discovery and potential of HA-stalkspecific antibodies largely remained unknown for some time [70] .
TextSentencer_T88 17314-17555 Sentence denotes An advantage over anti-HA head antibodies that are prone to escape mutations is that certain antistalk antibodies are less susceptible to mutations, as the stalk epitopes in the membrane-proximal region are critical for virus function [71] .
TextSentencer_T88 17314-17555 Sentence denotes An advantage over anti-HA head antibodies that are prone to escape mutations is that certain antistalk antibodies are less susceptible to mutations, as the stalk epitopes in the membrane-proximal region are critical for virus function [71] .
TextSentencer_T89 17556-17886 Sentence denotes Rather than attempt to directly induce such broadly neutralizing antibodies in humans by vaccination, which is limited to finding an appropriate immunogen with approved adjuvants, such antibodies may be more practically and effectively generated in naïve donor animals with optimal vaccination protocols for prophylaxis in humans.
TextSentencer_T89 17556-17886 Sentence denotes Rather than attempt to directly induce such broadly neutralizing antibodies in humans by vaccination, which is limited to finding an appropriate immunogen with approved adjuvants, such antibodies may be more practically and effectively generated in naïve donor animals with optimal vaccination protocols for prophylaxis in humans.
TextSentencer_T90 17887-18036 Sentence denotes However, knowledge of the protective coverage, dosage, and route of administration of such antibodies needs to be gained from further investigations.
TextSentencer_T90 17887-18036 Sentence denotes However, knowledge of the protective coverage, dosage, and route of administration of such antibodies needs to be gained from further investigations.
TextSentencer_T91 18037-18197 Sentence denotes Monoclonal neutralizing antibodies cross protective against H1, H2, H5, H6, and H9 influenza virus strains were recovered from human IgM + memory B cells [72] .
TextSentencer_T91 18037-18197 Sentence denotes Monoclonal neutralizing antibodies cross protective against H1, H2, H5, H6, and H9 influenza virus strains were recovered from human IgM + memory B cells [72] .
TextSentencer_T92 18198-18359 Sentence denotes Human monoclonal antibodies have also been identified with broadspectrum prophylactic efficacy against HPAI H5N1 influenza viruses in mice and ferrets [73, 74] .
TextSentencer_T92 18198-18359 Sentence denotes Human monoclonal antibodies have also been identified with broadspectrum prophylactic efficacy against HPAI H5N1 influenza viruses in mice and ferrets [73, 74] .
TextSentencer_T93 18360-18563 Sentence denotes Memory from past exposure to H1N1 influenza virus strains was also apparent in heterovariant immunity of individuals over 30 years of age rather than those younger during the H1N1 pandemic in 2009 [75] .
TextSentencer_T93 18360-18563 Sentence denotes Memory from past exposure to H1N1 influenza virus strains was also apparent in heterovariant immunity of individuals over 30 years of age rather than those younger during the H1N1 pandemic in 2009 [75] .
TextSentencer_T94 18564-18772 Sentence denotes Various monoclonal IgG antibodies against HA epitopes have been investigated for broad-spectrum prophylaxis in mice and their efficacy compared to the antivirals, amantadine, oseltamivir, and zanamivir [76] .
TextSentencer_T94 18564-18772 Sentence denotes Various monoclonal IgG antibodies against HA epitopes have been investigated for broad-spectrum prophylaxis in mice and their efficacy compared to the antivirals, amantadine, oseltamivir, and zanamivir [76] .
TextSentencer_T95 18773-19126 Sentence denotes Use of humanized and chimeric virus-specific monoclonal antibodies [77] and Fab fragments has been explored in recent years to circumvent immunogenicity issues and address suitability of such antibodies for broad-spectrum passive prophylaxis; however their development and supply may not be practical and cost effective in pandemic control of influenza.
TextSentencer_T95 18773-19126 Sentence denotes Use of humanized and chimeric virus-specific monoclonal antibodies [77] and Fab fragments has been explored in recent years to circumvent immunogenicity issues and address suitability of such antibodies for broad-spectrum passive prophylaxis; however their development and supply may not be practical and cost effective in pandemic control of influenza.
TextSentencer_T96 19127-19349 Sentence denotes Furthermore, the optimal dose and mode of delivery of a single monoclonal antibody preparation to the stalk domain are issues, with much higher titres needed for parenteral delivery as opposed to intranasal delivery [78] .
TextSentencer_T96 19127-19349 Sentence denotes Furthermore, the optimal dose and mode of delivery of a single monoclonal antibody preparation to the stalk domain are issues, with much higher titres needed for parenteral delivery as opposed to intranasal delivery [78] .
TextSentencer_T97 19350-19501 Sentence denotes Polyclonal antibodies with high affinity targeting multiple epitopes of the viral HA protein are under substantial investigation for influenza control.
TextSentencer_T97 19350-19501 Sentence denotes Polyclonal antibodies with high affinity targeting multiple epitopes of the viral HA protein are under substantial investigation for influenza control.
TextSentencer_T98 19502-19641 Sentence denotes IgG antibodies have been shown to play a major role in protection of ferrets from homologous and heterologous H5N1 influenza viruses [79] .
TextSentencer_T98 19502-19641 Sentence denotes IgG antibodies have been shown to play a major role in protection of ferrets from homologous and heterologous H5N1 influenza viruses [79] .
TextSentencer_T99 19642-19818 Sentence denotes As mentioned before, select regions of the head and stalk domains of the HA molecule are highly conserved and can induce cross protective antibody responses, albeit suboptimal.
TextSentencer_T99 19642-19818 Sentence denotes As mentioned before, select regions of the head and stalk domains of the HA molecule are highly conserved and can induce cross protective antibody responses, albeit suboptimal.
TextSentencer_T100 19819-19999 Sentence denotes As the HA head is immunodominant, stalk antigens have relatively low immunogenicity and do not stimulate large amounts of highly reactive antibodies with classical vaccine regimes.
TextSentencer_T100 19819-19999 Sentence denotes As the HA head is immunodominant, stalk antigens have relatively low immunogenicity and do not stimulate large amounts of highly reactive antibodies with classical vaccine regimes.
TextSentencer_T101 20000-20213 Sentence denotes However, broadly neutralizing high affinity antibodies could potentially be prepared in animals with immune manipulation using modified vaccine regimes and better adjuvants than those licensed for human use [80] .
TextSentencer_T101 20000-20213 Sentence denotes However, broadly neutralizing high affinity antibodies could potentially be prepared in animals with immune manipulation using modified vaccine regimes and better adjuvants than those licensed for human use [80] .
TextSentencer_T102 20214-20487 Sentence denotes Vaccination of naïve animals to generate heterologous polyclonal antibodies has benefits in targeting responses to potential key epitopes, since preexisting memory B cells with specificities for other immunodominant epitopes are not present to outcompete the naïve B cells.
TextSentencer_T102 20214-20487 Sentence denotes Vaccination of naïve animals to generate heterologous polyclonal antibodies has benefits in targeting responses to potential key epitopes, since preexisting memory B cells with specificities for other immunodominant epitopes are not present to outcompete the naïve B cells.
TextSentencer_T103 20488-20743 Sentence denotes As an example, prime-boost vaccination strategies have been found to increase neutralizing antibody titers 30-to 50-fold and reduce lung virus loads by 2 logs [81] [82] [83] , expanding the number and diversity of activated HAspecific CD4 + T cell clones.
TextSentencer_T103 20488-20743 Sentence denotes As an example, prime-boost vaccination strategies have been found to increase neutralizing antibody titers 30-to 50-fold and reduce lung virus loads by 2 logs [81] [82] [83] , expanding the number and diversity of activated HAspecific CD4 + T cell clones.
TextSentencer_T104 20744-20969 Sentence denotes Although universal vaccination in humans is the ultimate goal [84, 85] , broadly neutralizing antibodies produced in a large animal donor with strategic vaccination regimes would be useful as an interim therapy for influenza.
TextSentencer_T104 20744-20969 Sentence denotes Although universal vaccination in humans is the ultimate goal [84, 85] , broadly neutralizing antibodies produced in a large animal donor with strategic vaccination regimes would be useful as an interim therapy for influenza.
TextSentencer_T105 20970-21114 Sentence denotes Heterologous antibodies could be passively administered by the intranasal route to provide immediate protection of the respiratory tract mucosa.
TextSentencer_T105 20970-21114 Sentence denotes Heterologous antibodies could be passively administered by the intranasal route to provide immediate protection of the respiratory tract mucosa.
TextSentencer_T106 21115-21292 Sentence denotes Intranasal delivery of broadly neutralizing antibodies has been investigated in mice affording protection [86] [87] [88] [89] and warrants further studies in preclinical models.
TextSentencer_T106 21115-21292 Sentence denotes Intranasal delivery of broadly neutralizing antibodies has been investigated in mice affording protection [86] [87] [88] [89] and warrants further studies in preclinical models.
TextSentencer_T107 21293-21488 Sentence denotes Vaccination of large ruminant animals, such as dairy cows, is currently being considered and has the potential to supply a bulk source of milk-derived neutralizing antibodies for clinical trials.
TextSentencer_T107 21293-21488 Sentence denotes Vaccination of large ruminant animals, such as dairy cows, is currently being considered and has the potential to supply a bulk source of milk-derived neutralizing antibodies for clinical trials.
TextSentencer_T108 21489-21723 Sentence denotes Clearly, many unanswered questions regarding efficacy of routes of administration, dosage, timing, and immune memory to reexposure need to be addressed in future investigations of antistalk HA antibody-based prophylaxis for influenza.
TextSentencer_T108 21489-21723 Sentence denotes Clearly, many unanswered questions regarding efficacy of routes of administration, dosage, timing, and immune memory to reexposure need to be addressed in future investigations of antistalk HA antibody-based prophylaxis for influenza.
TextSentencer_T109 21724-21969 Sentence denotes Despite modern advances in vaccine technology with the availability of antivirals and antibiotics and improved global surveillance of influenza virus, a contemporary pandemic may have a worse case scenario than that which occurred in 1918 [90] .
TextSentencer_T109 21724-21969 Sentence denotes Despite modern advances in vaccine technology with the availability of antivirals and antibiotics and improved global surveillance of influenza virus, a contemporary pandemic may have a worse case scenario than that which occurred in 1918 [90] .
TextSentencer_T110 21970-22169 Sentence denotes Compounding these factors is civil unrest and the existence of poor medical infrastructure in overcrowded developing countries, likely to be the epicenter of newly emerging influenza virus outbreaks.
TextSentencer_T110 21970-22169 Sentence denotes Compounding these factors is civil unrest and the existence of poor medical infrastructure in overcrowded developing countries, likely to be the epicenter of newly emerging influenza virus outbreaks.
TextSentencer_T111 22170-22294 Sentence denotes Clearly, intervention needs to be early, effective, and robust in the effort to curtail morbidity and mortality (Figure 3 ).
TextSentencer_T111 22170-22294 Sentence denotes Clearly, intervention needs to be early, effective, and robust in the effort to curtail morbidity and mortality (Figure 3 ).
TextSentencer_T112 22295-22444 Sentence denotes Antibody-based passive immunity is a powerful prophylactic strategy for influenza pandemic control, reducing the risk of virus spread in populations.
TextSentencer_T112 22295-22444 Sentence denotes Antibody-based passive immunity is a powerful prophylactic strategy for influenza pandemic control, reducing the risk of virus spread in populations.
TextSentencer_T113 22445-22625 Sentence denotes Ideally, an antibody-based therapy could be self-administered, via either an inhaler or intranasal spray for protective coverage of the airways during the first wave of a pandemic.
TextSentencer_T113 22445-22625 Sentence denotes Ideally, an antibody-based therapy could be self-administered, via either an inhaler or intranasal spray for protective coverage of the airways during the first wave of a pandemic.
TextSentencer_T114 22626-22768 Sentence denotes The dairy industry infrastructure in some countries (e.g., Australia) provides an opportunity for bulk antibody production in large ruminants.
TextSentencer_T114 22626-22768 Sentence denotes The dairy industry infrastructure in some countries (e.g., Australia) provides an opportunity for bulk antibody production in large ruminants.
TextSentencer_T115 22769-23013 Sentence denotes One may speculate that if a single 50 mg dose of potent broadly neutralizing antibodies could be effective over a 7-day duration, coverage for 3 months would require 12 doses that possibly could be distributed to families and self-administered.
TextSentencer_T115 22769-23013 Sentence denotes One may speculate that if a single 50 mg dose of potent broadly neutralizing antibodies could be effective over a 7-day duration, coverage for 3 months would require 12 doses that possibly could be distributed to families and self-administered.
TextSentencer_T116 23014-23033 Sentence denotes Assuming Figure 3 :
TextSentencer_T116 23014-23033 Sentence denotes Assuming Figure 3 :
TextSentencer_T117 23034-23118 Sentence denotes Modeling of the impact of prophylaxis on mortality curves during pandemic influenza.
TextSentencer_T117 23034-23118 Sentence denotes Modeling of the impact of prophylaxis on mortality curves during pandemic influenza.
TextSentencer_T118 23119-23220 Sentence denotes Prophylaxis could protect against both morbidity and mortality rates by lowering the number of cases.
TextSentencer_T118 23119-23220 Sentence denotes Prophylaxis could protect against both morbidity and mortality rates by lowering the number of cases.
TextSentencer_T119 23221-23436 Sentence denotes Effective passive immunity is important to provide coverage during the first wave or six-month risk period of the pandemic whilst an effective vaccine is developed for the identified virus to induce active immunity.
TextSentencer_T119 23221-23436 Sentence denotes Effective passive immunity is important to provide coverage during the first wave or six-month risk period of the pandemic whilst an effective vaccine is developed for the identified virus to induce active immunity.
TextSentencer_T120 23437-23582 Sentence denotes average annual milk production of 6,000 L/cow, it is feasible that approximately 6 kg of immunoglobulin (10,000 doses) could be produced per cow.
TextSentencer_T120 23437-23582 Sentence denotes average annual milk production of 6,000 L/cow, it is feasible that approximately 6 kg of immunoglobulin (10,000 doses) could be produced per cow.
TextSentencer_T121 23583-23915 Sentence denotes In addition to those susceptible and at high risk of exposure, an immunoprophylaxis option would also be particularly important for those who have been previously vaccinated with seasonal influenza and may be unresponsive to pandemic influenza vaccination due to a transient antiviral state, recently termed innate imprinting [91] .
TextSentencer_T121 23583-23915 Sentence denotes In addition to those susceptible and at high risk of exposure, an immunoprophylaxis option would also be particularly important for those who have been previously vaccinated with seasonal influenza and may be unresponsive to pandemic influenza vaccination due to a transient antiviral state, recently termed innate imprinting [91] .
TextSentencer_T122 23916-24146 Sentence denotes Monoclonal antibody-based immunotherapy with broadly neutralizing capabilities and universal anti-influenza vaccines show promise for influenza prophylaxis, affording protection of the respiratory tract mucosa (reviewed in [92] ).
TextSentencer_T122 23916-24146 Sentence denotes Monoclonal antibody-based immunotherapy with broadly neutralizing capabilities and universal anti-influenza vaccines show promise for influenza prophylaxis, affording protection of the respiratory tract mucosa (reviewed in [92] ).
TextSentencer_T123 24147-24343 Sentence denotes Interest in polyclonal antibody-based immunotherapy has recently been reignited with a study showing neutralizing efficacy of antistalk antibodies with new modes of action in a ferret model [93] .
TextSentencer_T123 24147-24343 Sentence denotes Interest in polyclonal antibody-based immunotherapy has recently been reignited with a study showing neutralizing efficacy of antistalk antibodies with new modes of action in a ferret model [93] .
TextSentencer_T124 24344-24682 Sentence denotes The prospects of producing bulk supplies of antibodies in large production animals present a strategic approach, likely to generate a more robust antibody response in the donor animal, which can be passively transferred, than that directly induced by natural virus infection or currently licensed vaccines and adjuvants for use in humans.
TextSentencer_T124 24344-24682 Sentence denotes The prospects of producing bulk supplies of antibodies in large production animals present a strategic approach, likely to generate a more robust antibody response in the donor animal, which can be passively transferred, than that directly induced by natural virus infection or currently licensed vaccines and adjuvants for use in humans.
TextSentencer_T125 24683-24968 Sentence denotes As an alternative to animal-based production of antibodies, the expression of therapeutic antibodies in tobacco plants has also recently been of interest for treatment of the current Ebola virus outbreak in West Africa [94] , although scaleup for adequate supplies may be a limitation.
TextSentencer_T125 24683-24968 Sentence denotes As an alternative to animal-based production of antibodies, the expression of therapeutic antibodies in tobacco plants has also recently been of interest for treatment of the current Ebola virus outbreak in West Africa [94] , although scaleup for adequate supplies may be a limitation.
TextSentencer_T126 24969-25160 Sentence denotes In a preclinical model, we have investigated intranasal delivery of ruminant polyclonal antibodies to protect the respiratory mucosa of mice against infection with H1N1 influenza virus [95] .
TextSentencer_T126 24969-25160 Sentence denotes In a preclinical model, we have investigated intranasal delivery of ruminant polyclonal antibodies to protect the respiratory mucosa of mice against infection with H1N1 influenza virus [95] .
TextSentencer_T127 25161-25282 Sentence denotes We found that exogenous IgG, derived from H1N1-immunized sheep, as a model ruminant, protected mice upon virus challenge.
TextSentencer_T127 25161-25282 Sentence denotes We found that exogenous IgG, derived from H1N1-immunized sheep, as a model ruminant, protected mice upon virus challenge.
TextSentencer_T128 25283-25448 Sentence denotes Protection was Fc-independent, was effective up to 3 days before virus exposure, and largely prevented infection in the lungs and preserved normal lung architecture.
TextSentencer_T128 25283-25448 Sentence denotes Protection was Fc-independent, was effective up to 3 days before virus exposure, and largely prevented infection in the lungs and preserved normal lung architecture.
TextSentencer_T129 25449-25775 Sentence denotes A benefit of intranasal administration is the direct noninvasive delivery of antibody to the lumen of the respiratory mucosa, whereas in a natural influenza virus infection, the presence of IgG in the airways is derived from circulating antibody by transudation with IgM and IgA transported across the epithelium to the lumen.
TextSentencer_T129 25449-25775 Sentence denotes A benefit of intranasal administration is the direct noninvasive delivery of antibody to the lumen of the respiratory mucosa, whereas in a natural influenza virus infection, the presence of IgG in the airways is derived from circulating antibody by transudation with IgM and IgA transported across the epithelium to the lumen.
TextSentencer_T130 25776-26005 Sentence denotes Investigations of antistalk antibody isotypes and subclasses generated in immunized donor animals are required to increase knowledge of optimal efficacy and cross protection against clades spanning H1, H3, H7, and H9 virus types.
TextSentencer_T130 25776-26005 Sentence denotes Investigations of antistalk antibody isotypes and subclasses generated in immunized donor animals are required to increase knowledge of optimal efficacy and cross protection against clades spanning H1, H3, H7, and H9 virus types.
TextSentencer_T131 26006-26152 Sentence denotes Antiviral prevention strategies for control of newly emerging or reemerged influenza virus strains of pandemic potential are of utmost importance.
TextSentencer_T131 26006-26152 Sentence denotes Antiviral prevention strategies for control of newly emerging or reemerged influenza virus strains of pandemic potential are of utmost importance.
TextSentencer_T132 26153-26459 Sentence denotes Whilst intense efforts are being made to meet the urgent need for a universal vaccine eliciting long-term immunity, passive immunoprophylaxis would have benefits of immediate short-term protection, especially of benefit to the elderly and very young ones, who have poorer antibody responses to vaccination.
TextSentencer_T132 26153-26459 Sentence denotes Whilst intense efforts are being made to meet the urgent need for a universal vaccine eliciting long-term immunity, passive immunoprophylaxis would have benefits of immediate short-term protection, especially of benefit to the elderly and very young ones, who have poorer antibody responses to vaccination.
TextSentencer_T133 26460-26626 Sentence denotes Control of influenza with antiviral drugs lowers the risk of complications [96] but drug resistance can develop, with adamantanes no longer recommended for use [20] .
TextSentencer_T133 26460-26626 Sentence denotes Control of influenza with antiviral drugs lowers the risk of complications [96] but drug resistance can develop, with adamantanes no longer recommended for use [20] .
TextSentencer_T134 26627-26760 Sentence denotes Furthermore, costeffective management in low resource settings is problematic in many endemic regions, especially in South East Asia.
TextSentencer_T134 26627-26760 Sentence denotes Furthermore, costeffective management in low resource settings is problematic in many endemic regions, especially in South East Asia.
TextSentencer_T135 26761-26861 Sentence denotes Broad-spectrum immunoprophylaxis holds future promise as an effective control measure for influenza.
TextSentencer_T135 26761-26861 Sentence denotes Broad-spectrum immunoprophylaxis holds future promise as an effective control measure for influenza.
TextSentencer_T136 26862-27196 Sentence denotes Preparation of broadly neutralizing antibodies in naïve animal donors is potentially inexpensive and independent of host immune memory to influenza viruses, where dominant responses from HA-specific memory B cells are often induced by vaccination or natural infection, a phenomenon first described as original antigenic sin [97, 98] .
TextSentencer_T136 26862-27196 Sentence denotes Preparation of broadly neutralizing antibodies in naïve animal donors is potentially inexpensive and independent of host immune memory to influenza viruses, where dominant responses from HA-specific memory B cells are often induced by vaccination or natural infection, a phenomenon first described as original antigenic sin [97, 98] .
TextSentencer_T137 27197-27440 Sentence denotes In conclusion, serious concerns may be mitigated by passive immunoprophylaxis using broadly neutralizing antibodies that provide universal coverage against multiple influenza viruses, providing an interim control option for pandemic influenza.
TextSentencer_T137 27197-27440 Sentence denotes In conclusion, serious concerns may be mitigated by passive immunoprophylaxis using broadly neutralizing antibodies that provide universal coverage against multiple influenza viruses, providing an interim control option for pandemic influenza.
TextSentencer_T138 27441-27501 Sentence denotes The authors declare that there are no conflict of interests.
TextSentencer_T138 27441-27501 Sentence denotes The authors declare that there are no conflict of interests.