LitCovid-sentences  

PMC:7376974 / 75353-93309 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T472 0-34 Sentence denotes Interaction with the Immune System
T473 35-171 Sentence denotes The vast majority of the studies show that human survival to viral attack is based on the stimulation and response of our immune system.
T474 172-321 Sentence denotes When a virus enters and starts infecting tissues, the body reacts and triggers a strong immune response to overcome the pathogen invasion and spread.
T475 322-381 Sentence denotes Normally, two different immunological reactions take place.
T476 382-1069 Sentence denotes The oxidative stress induced by infection causes the activation of the inflammasome through upregulation of pro-inflammatory cytokines such as IL-1β, pro-IL-18, and NLRP3.122 Excessive upregulation of this mechanism leads to cell damage and eventually to pyroptosis activated by caspases.122 It was also shown that generation of radicals is able to depolarize mitochondria, hence affecting host cell respiration and inducing ROS-mediated apoptosis at the late stage of infection.123 Besides, activation of pro-inflammatory cytokines can alert the immune system blocking the infection (the innate immune response).122 The second immune response is specific (the adaptive immune response).
T477 1070-1205 Sentence denotes Immune cells are trained to attack the virus (cellular response), while specific antibodies are produced by B cells (humoral response).
T478 1206-1339 Sentence denotes In the last years, HNMs were proved to tune the immune responses, demonstrating to be a possible alternative against viral infection.
T479 1340-1484 Sentence denotes In this section the most relevant strategies for the activation of innate and adaptive immune responses using NMs will be described (Figure 14).
T480 1485-1551 Sentence denotes Figure 14 Illustration of HNM interaction with the immune system.
T481 1552-1654 Sentence denotes Left: HNMs can enhance the production of interferon (IFN) alerting the immune system of the infection.
T482 1655-1661 Sentence denotes Right:
T483 1662-1859 Sentence denotes Virus-mimicking particles composed of viral proteins and HNMs can induce a strong immunological response activating dendritic cells, T cells, and stimulating B cells to produce specific antibodies.
T484 1861-1883 Sentence denotes Innate Immune Response
T485 1884-1987 Sentence denotes Innate immune response is the first response that takes place in the presence of any type of infection.
T486 1988-2384 Sentence denotes During this early stage, interferon stimulating genes (ISGs) are upregulated in the infected cells.125 This self-defense mechanism slows down the viral replication and alerts sentinel immune cells that start producing proinflammatory cytokines and trigger inflammation.125 However, many viruses are able to escape this complex mechanism, retarding the immune response and spreading the infection.
T487 2385-2463 Sentence denotes The interaction of HNMs with the immune system has been more and more studied.
T488 2464-2628 Sentence denotes In the case of antiviral HNMs, many examples can be found in the literature where the NMs not only slow down the infection but also tune the innate immune response.
T489 2629-2686 Sentence denotes Certain HMNs can display an intrinsic immune stimulation.
T490 2687-2969 Sentence denotes We have already mentioned above that in the early stage of infection, AgNPs mainly prevent the virus from entering the host cell through the interaction with the external capsid, but in vitro cellular experiments lack to understand the complex interaction with primary immune cells.
T491 2970-3174 Sentence denotes Recent studies have shown that AgNPs can potentially induce the expression of genes involved in innate and adaptive immunity-associated pathways, which are known to play crucial role in immune regulation.
T492 3175-3813 Sentence denotes For example, Toll-like receptor 7 can be upregulated by AgNPs after 24 h, by recognizing the single-stranded RNA of the viruses and regulating the antiviral immune response.126 Another study showed that in RSV-infected mice treated with AgNPs, the particles reduced the production of pro-inflammatory TNF-α and IL-6 cytokines, but potentiated the anti-RSV activity of neutrophils in an experimental mouse model.127 However, activation of AgNPs in the reduction of RSV has been noted only when the NM was intranasally inoculated together with the virus, and no results have been reported on the use of AgNPs administrated on infected mice.
T493 3814-4000 Sentence denotes In the case of influenza virus infection of lung epithelial cells, it was found that AgNPs targeted infected lung epithelial cells and reduced viral replication, by preventing autophagy.
T494 4001-4116 Sentence denotes However, the blockage of the autophagic flux by AgNPs does not inhibit viral replication in already infected cells.
T495 4117-4500 Sentence denotes Therefore, AgNPs are more suitable as viral preventive agents due to their pro-inflammatory response rather than drugs.128 More recently, AgNPs were combined with graphene materials and exploited as antiviral material for the treatment of Porcine reproductive and respiratory syndrome virus (PRRSV).129 GO-AgNPs were able to clump the virus diminishing its fusion with cell membrane.
T496 4501-4671 Sentence denotes Additionally, once GO-AgNPs were internalized in host cells, they stimulated the ISGs that blocked viral budding and its diffusion to other cells in vitro (Figure 15).129
T497 4672-4762 Sentence denotes Figure 15 Scheme of the mechanism of action of GO-AgNPs on activation of innate immunity.
T498 4763-4805 Sentence denotes Reproduced with permission from ref (129).
T499 4806-4848 Sentence denotes Copyright 2018 American Chemistry Society.
T500 4849-5492 Sentence denotes Similarly, CDs used for the treatment of RSV and PRRSV were able to activate the innate immune response via an upregulation of ISGs in vitro.130 Gold nanorods were applied to boost the innate immune response against RSV in vivo.131 Interestingly, it was shown that these nanorods (when intranasally administered with RSV) were not only able to activate the ISGs but also to tune the production of pro- and anti-inflammatory cytokines, resulting in the blocking of the infection with a reduced pulmonary inflammation.131 As drug carriers, HNMs can also affect the internalization pathways, modulate drug efficacy, and the immune cell responses.
T501 5493-5810 Sentence denotes For instance, it was found that the isoprinosine immunomodulatory antiviral drug displays a much higher antiviral efficacy in vivo when delivered with CNTs than as a pure drug (in zebrafish larvae food administration), probably due to a better cellular uptake and the anti-inflammatory properties of the nanotubes.132
T502 5811-6259 Sentence denotes Fullerenes also exhibit immunomodulation properties through the release of cytokines by bovine alveolar macrophages.133 A study explored the influence of functionalization of C60 with molecules presenting different surface charges like hydroxyl groups and amino acids.134 The study concluded that negative charges upregulated TNF-α up-secretion in RAW 264.7 macrophages, but highly positively or negatively charged surfaces increased cell toxicity.
T503 6260-6362 Sentence denotes The upregulation of the cytokine TNF-α is a proof that fullerene can promote cellular immune response.
T504 6363-6512 Sentence denotes Despite these preliminary results, the actual mechanisms of interaction between HNMs and the immune system are still at early stage of understanding.
T505 6513-6603 Sentence denotes We must consider that the immune response needs to be proportional to the infection grade.
T506 6604-6851 Sentence denotes If on one side nanosized immuno-boosters can alert more efficiently the sentinel cells, the use of HNMs that trigger an exaggerated immune response can promote excessive inflammation, damaging healthy cells and promoting uncontrolled side effects.
T507 6852-7071 Sentence denotes In the particular context of SARS-Cov-2, the use of AgNPs, fullerenes, or other pro-inflammatory HNMs at the middle and late infection stage may cause an aggravation of the symptoms due to already diffused inflammation.
T508 7072-7514 Sentence denotes In particular, most of the studies showed the ability to reduce infection when HNMs were first incubated with the pathogenic virus, thus limiting their potential use in the early stage infection.124 The formulation of HNMs able to both alert the immune system (e.g., upregulating cytokine) and control lung inflammation (e.g., ROS scavenger) even after the early stage infection may be a possible strategy for treatments against SARS viruses.
T509 7516-7540 Sentence denotes Adaptive Immune Response
T510 7541-7639 Sentence denotes Adaptive immune response is the specific response that the immune system exerts against pathogens.
T511 7640-8103 Sentence denotes This mechanism is particularly active toward viral infections where the immune system produces specialized lymphocytes (to fight the virus), called memory B cells (to be effective in case of new infections) and antibodies (corresponding to the humoral response).135 The stimulation of adaptive responses in case of specific infections can be induced artificially through the introduction of attenuated pathogens, stimulating the production of specific antibodies.
T512 8104-8512 Sentence denotes This is the principle of vaccination, which is the most common procedure for immunization of large areas of population against many kinds of lethal viruses.135 Besides, the use of viral proteins as antigens in the vaccine formulation leads to neutralizing antibodies, but, due to the low immunogenicity of isolated proteins, does not always stimulate sufficiently the immune system to reach total protection.
T513 8513-8616 Sentence denotes More recently, nanotechnology has been applied to develop more efficient vaccines (e.g., nanovaccines).
T514 8617-8947 Sentence denotes The use of nanostructures with a size similar to virus (virus-like nanoparticles) sensibly enhances the response helping to reach immunity.135 HNMs can adsorb viral particles and present them to the immune system.136,137 This method of vaccination has been successfully applied in vivo for the challenge of herpes simplex 2 virus.
T515 8948-9049 Sentence denotes HSV-2 starts its spreading in vaginal tissues and then diffuses to the neurons causing death in mice.
T516 9050-9246 Sentence denotes ZnO NPs (teardrop morphology), after vaginal inoculation with HSV-2, are able not only to prevent viral cell adhesion but also to expose viral antigens to T cells and DCs, leading to immunization.
T517 9247-9331 Sentence denotes The preclinical trials against HSV-2 showed a survival to infection higher than 90%.
T518 9332-9494 Sentence denotes This approach highlights the possibility to couple cell mimicking NMs to other co-adjuvants for the formulation of large spectrum nanovaccines (Figure 16).136,137
T519 9495-9850 Sentence denotes Figure 16 (A) Scanning electron microscopy images of ZnO tetrapod nanoparticles (ZOTEN) synthesized by flame transport synthesis. (B) Mice were challenged intravaginally with HSV-2 333 with or without ZOTEN. (C) To monitor progression of infection, mice were observed daily for the development of lesions around the vaginal opening, and base of the tail.
T520 9851-9918 Sentence denotes Representative images from three independent experiments are shown.
T521 9919-9961 Sentence denotes Reproduced with permission from ref (137).
T522 9962-10024 Sentence denotes Copyright 2016 the American Association of Immunologists, Inc.
T523 10025-10117 Sentence denotes HNMs have been also applied to the delivery of antigens, exposing them to the immune system.
T524 10118-10747 Sentence denotes Fullerenes were found as suitable carriers for the delivery of drugs or nucleic acids.138 Functionalized fullerene can also self-assemble into virus-sized NPs.139 Investigated as vaccines in cancer immune therapy,140 polyhydroxy fullerenes (called fullerenols) display interesting properties for antiviral therapy, based on their capacity to self-assemble into virus-like particles (VLPs) and so to enhance the immunogenicity of the antigens.141 The great advantage of this strategy relies on the easy encapsulation process during the self-assembly making fullerenols versatile for the formulation of different kinds of vaccines.
T525 10748-11171 Sentence denotes These VLPs were investigated against HIV-1141 and hepatitis C viruses.142 Compared to conventional protein- or peptide-based vaccines intended to induce antigen-specific adaptive immune responses, DNA vaccines are more stable, cost-effective, easy to manufacture, and safe in handling.143 However, DNA vaccines have the disadvantage of being poorly immunogenic.144 Fullerenol VLPs allow to avoid the use of other adjuvants.
T526 11172-11309 Sentence denotes In the case of a vaccine against HIV-1, fullerenol VLPs penetrated easily into the cells resulting in an enhancement of DNA transfection.
T527 11310-11540 Sentence denotes This was proved in a study using fullerenol encapsulating DNA encoding the HIV-1 envelope protein gp145 (Figure 17).141In vitro assays were performed in human embryonic kidney cells line (HEK293) showing good transfection ability.
T528 11541-11734 Sentence denotes Following various immunization routes (e.g., activation of Toll-like receptor signaling or effector memory T cell immune response), fullerenol VLPs can induce an innate and a cellular immunity.
T529 11735-11907 Sentence denotes A similar study was performed for hepatitis C using the HCV recombinant protein as antigen,142 confirming the potential efficacy of using fullerenols as antiviral vaccines.
T530 11908-11979 Sentence denotes Nevertheless, these results require further mechanistic investigations.
T531 11980-12277 Sentence denotes Indeed, in vitro studies also evidenced a suppressive effect of acquired immune response of C60 pyrrolidine tris-acid and fullerenol C60(OH)36.145 The fullerenol had a dose-dependent effect on T cell receptor-mediated activation and antibody production by B cells under anti-CD40/IL-4 stimulation.
T532 12278-12328 Sentence denotes However, the molecular mechanism is still unknown.
T533 12329-12958 Sentence denotes Figure 17 Use of fullerenol as co-adjuvant for vaccination. (a) The structure of fullerenol, red balls represent O and white for H on the fullerene surface, and green balls represent C atoms. (b) The schematic diagram of HIV Env plasmid DNA encapsulated during the self-assembly of fullerenol. (c) TEM image of Env entrapped by fullerenol. (d) Compared to naked Env immunization group, IFN-γ production (immunospot) was significantly enhanced when mice were immunized with the formulation via various immunization routes, including intradermal (i.d.), intramuscular (i.m.), subcutaneous (s.c.), and intranasal (i.n.) injections.
T534 12959-13035 Sentence denotes Fullerenol could decrease the antigen dosage (e) and immunization times (f).
T535 13036-13078 Sentence denotes Reproduced with permission from ref (141).
T536 13079-13117 Sentence denotes Copyright 2013 John Wiley & Sons, Inc.
T537 13118-13556 Sentence denotes Other HNMs including AuNPs (two subcutaneous injections in guinea pigs) and nanodiamonds (three subcutaneous injections in Balb/C mice) were explored as carriers of viral proteins for immunization of swine transmissible gastroenteritis virus and H7N9 influenza, respectively, with good preliminary results.146,147 In these cases, the vaccine formulation relies on the adsorption of the viral antigen onto the surface of the nanoparticles.
T538 13557-13618 Sentence denotes However, an effective vaccination depends on several factors.
T539 13619-13691 Sentence denotes First of all, the size of the NPs plays a key role on the immune system.
T540 13692-13925 Sentence denotes For instance, size-dependent vaccination efficacy has been reported in mice immunization against the foot-and-mouth disease virus (intraperitoneal and subcutaneous injection, every 7 days for 7 weeks) using AuNPs as antigen carriers.
T541 13926-14147 Sentence denotes In this study, the most effective activity to stimulate the immune system was exerted by particles with a diameter in the range of 8 nm.148 Both smaller or bigger particles evidenced a drop-off of the immunization effect.
T542 14148-14317 Sentence denotes This aspect cannot be ascribed to the antigen concentration, but must be associated only to the nanoparticle size; however, the mechanism of interaction remains unknown.
T543 14318-14410 Sentence denotes The selected antigen plays also a crucial role in the preparation of wide spectrum vaccines.
T544 14411-14549 Sentence denotes For instance, in the case of influenza, two major membrane glycoproteins, hemagglutinin and neuraminidase, are generally used as antigens.
T545 14550-14765 Sentence denotes However, the antibodies produced by this vaccination strategy are selective to the dominant epitope which has a low effectiveness or is totally ineffective against other epitopes or other kinds of influenza viruses.
T546 14766-14972 Sentence denotes M2 (a viral protein responsible for the budding and scission of the influenza virus) is commonly expressed in different types of influenza viruses with a high rate of conservation but with low antigenicity.
T547 14973-15103 Sentence denotes It has been shown that AuNPs functionalized with M2e protein have a high immunization capacity in comparison to the antigen alone.
T548 15104-15438 Sentence denotes Mice immunized with AuNPs (two intranasal injections), and then challenged, showed a survival rate higher than 90% to California-H1N1pdm, Victoria-H3N2, and Vietnam-H5N1 infections.149 This strategy shows that HNMs can be used to boost the immune response of low immunogenic molecules, providing a wide spectrum vaccination potential.
T549 15439-15671 Sentence denotes Unfortunately, it has not been determined if the budding process in SARS-Cov-2 is mediated by viral proteins or via the host cell’s endosomal sorting complex, thus more research on the SARS-Cov-2 viral machinery is highly desirable.
T550 15672-15886 Sentence denotes All these approaches are based on the capacity of the nanoparticles to adsorb the antigens and expose them to the immune system in the appropriate conformation to produce the neutralizing and protective antibodies.
T551 15887-15945 Sentence denotes However, the adsorption is not an easy process to control.
T552 15946-16196 Sentence denotes For instance, AuNPs have been ineffective in the immunization against SARS-Cov, when S viral proteins were used as antigens.150 In particular, the immunization with the protein alone was more efficient than when it was adsorbed onto the AuNP surface.
T553 16197-16351 Sentence denotes This failure was associated with a conformational change or denaturation of the antigen, which did not lead to the production of the specific antibody.150
T554 16352-17075 Sentence denotes Covalent chemistry strategies offer a higher control on the antigen quantification with higher reproducibility and possibility to bind different groups onto the surface of HNMs. For example, calcium phosphate nanoparticles (CaPNPs) were successfully covalently functionalized with Hen Egg lysozyme as model antigen showing an immunization 100 times higher in vivo compared to antigens alone using (one subdermal injection in mice).151 A similar approach was used with iron oxide NPs using mannose (to target DCs) and hepatitis B antigen showing good immunological activity in vitro (two subdermal injections in mice at 14 days distance).152 More recently, other types of vaccination strategies have been applied using HNMs.
T555 17076-17155 Sentence denotes A smart example has been reported using multifunctional CaPNPs on herpes virus.
T556 17156-17306 Sentence denotes In this study, CaPNPs have been covalently functionalized with alum/MPL as the adjuvant and two peptides as antigens selected via reverse vaccination.
T557 17307-17604 Sentence denotes The NM stimulated the immune system generating highly efficient antibodies able to block cell-to-cell infection of herpes virus in vivo (three intramuscular injections in mice every 14 days), increasing the survival rate of immunized mice to 100% against the controls (20% survival, Figure 18).153
T558 17605-17650 Sentence denotes Figure 18 Scheme of CaPNPs used for vaccine.
T559 17651-17656 Sentence denotes Left:
T560 17657-17737 Sentence denotes CaPNPs functionalized with CpGm adjuvant and two different peptides as antigens.
T561 17738-17748 Sentence denotes Top right:
T562 17749-17811 Sentence denotes CaPNPs were able to reduce cell-to-cell virus spread in vitro.
T563 17812-17825 Sentence denotes Bottom right:
T564 17826-17884 Sentence denotes CaP nanovaccines were able to immunize mice against HSV-1.
T565 17885-17927 Sentence denotes Reproduced with permission from ref (153).
T566 17928-17956 Sentence denotes Copyright 2019 Elsevier B.V.