Journal of Clinical Medicine

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16 pages, 3765 KiB

Open AccessArticle

Local Serpin Treatment via Chitosan-Collagen Hydrogel after Spinal Cord Injury Reduces Tissue Damage and Improves Neurologic Function

by Jacek M. Kwiecien, Liqiang Zhang, Jordan R. Yaron, Lauren N. Schutz, Christian J. Kwiecien-Delaney, Enkidia A. Awo, Michelle Burgin, Wojciech Dabrowski and Alexandra R. Lucas

J. Clin. Med. 2020, 9(4), 1221; https://doi.org/10.3390/jcm9041221 - 23 Apr 2020

Cited by 27 | Viewed by 4183

Abstract

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury [...] Read more.

Spinal cord injury (SCI) results in massive secondary damage characterized by a prolonged inflammation with phagocytic macrophage invasion and tissue destruction. In prior work, sustained subdural infusion of anti-inflammatory compounds reduced neurological deficits and reduced pro-inflammatory cell invasion at the site of injury leading to improved outcomes. We hypothesized that implantation of a hydrogel loaded with an immune modulating biologic drug, Serp-1, for sustained delivery after crush-induced SCI would have an effective anti-inflammatory and neuroprotective effect. Rats with dorsal column SCI crush injury, implanted with physical chitosan-collagen hydrogels (CCH) had severe granulomatous infiltration at the site of the dorsal column injury, which accumulated excess edema at 28 days post-surgery. More pronounced neuroprotective changes were observed with high dose (100 µg/50 µL) Serp-1 CCH implanted rats, but not with low dose (10 µg/50 µL) Serp-1 CCH. Rats treated with Serp-1 CCH implants also had improved motor function up to 20 days with recovery of neurological deficits attributed to inhibition of inflammation-associated tissue damage. In contrast, prolonged low dose Serp-1 infusion with chitosan did not improve recovery. Intralesional implantation of hydrogel for sustained delivery of the Serp-1 immune modulating biologic offers a neuroprotective treatment of acute SCI. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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22 pages, 5458 KiB

Open AccessArticle

Orf Virus IL-10 and VEGF-E Act Synergistically to Enhance Healing of Cutaneous Wounds in Mice

by Lyn M. Wise, Gabriella S. Stuart, Nicola C. Jones, Stephen B. Fleming and Andrew A. Mercer

J. Clin. Med. 2020, 9(4), 1085; https://doi.org/10.3390/jcm9041085 - 11 Apr 2020

Cited by 13 | Viewed by 4500

Abstract

Orf virus (OV) is a zoonotic parapoxvirus that causes highly proliferative skin lesions which resolve with minimal inflammation and scarring. OV encodes two immunomodulators, vascular endothelial growth factor (VEGF)-E and interleukin-10 (ovIL-10), which individually modulate skin repair and inflammation. This study examined the [...] Read more.

Orf virus (OV) is a zoonotic parapoxvirus that causes highly proliferative skin lesions which resolve with minimal inflammation and scarring. OV encodes two immunomodulators, vascular endothelial growth factor (VEGF)-E and interleukin-10 (ovIL-10), which individually modulate skin repair and inflammation. This study examined the effects of the VEGF-E and ovIL-10 combination on healing processes in a murine wound model. Treatments with viral proteins, individually and in combination, were compared to a mammalian VEGF-A and IL-10 combination. Wound biopsies were harvested to measure re-epithelialisation and scarring (histology), inflammation, fibrosis and angiogenesis (immunofluorescence), and gene expression (quantitative polymerase chain reaction). VEGF-E and ovIL-10 showed additive effects on wound closure and re-epithelialisation, and suppressed M1 macrophage and myofibroblast infiltration, while allowing M2 macrophage recruitment. The viral combination also increased endothelial cell density and pericyte coverage, and improved collagen deposition while reducing the scar area. The mammalian combination showed equivalent effects on wound closure, re-epithelialisation and fibrosis, but did not promote blood vessel stabilisation or collagen remodeling. The combination treatments also differentially altered the expression of transforming growth factor beta isoforms, Tgfβ1 and Tgfβ3. These findings show that the OV proteins synergistically enhance skin repair, and act in a complimentary fashion to improve scar quality. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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15 pages, 2139 KiB

Open AccessArticle

Addition of a Viral Immunomodulatory Domain to Etanercept Generates a Bifunctional Chemokine and TNF Inhibitor

by Alí Alejo, Carolina Sánchez, Sylvie Amu, Padraic G. Fallon and Antonio Alcamí

J. Clin. Med. 2020, 9(1), 25; https://doi.org/10.3390/jcm9010025 - 20 Dec 2019

Cited by 5 | Viewed by 2856

Abstract

The inhibition of tumor necrosis factor (TNF) through the use of either antibodies or soluble receptors is a highly effective strategy for the clinical control of chronic inflammatory conditions such as rheumatoid arthritis. Different viruses have similarly exploited this concept by expressing a [...] Read more.

The inhibition of tumor necrosis factor (TNF) through the use of either antibodies or soluble receptors is a highly effective strategy for the clinical control of chronic inflammatory conditions such as rheumatoid arthritis. Different viruses have similarly exploited this concept by expressing a set of specifically tailored secreted TNF decoy receptors to block host inflammatory responses. Poxviruses have been shown to encode at least two distinct molecules, termed Cytokine response modifier D (CrmD) and CrmB, in which a TNF inhibitor is combined with a chemokine inhibitor on the same molecule. The ectromelia virus CrmD protein was found to be a critical determinant of virulence in vivo, being able to control local inflammation to allow further viral spread and the establishment of a lethal infection. Strikingly, both the TNF and the chemokine inhibitory domains are required for the full activity of CrmD, suggesting a model in which inhibition of TNF is supported by the concomitant blockade of a reduced set of chemokines. Inspired by this model, we reasoned that a similar strategy could be applied to modify the clinically used human TNF receptor (etanercept), producing a generation of novel, more effective therapeutic agents. Here we show the analysis of a set of fusion proteins derived from etanercept by addition of a viral chemokine-binding protein. A bifunctional inhibitor capable of binding to and blocking the activity of TNF as well as a set of chemokines is generated that is active in the prevention of arthritis in a murine disease model. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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17 pages, 3590 KiB

Open AccessArticle

AAV Mediated Delivery of Myxoma Virus M013 Gene Protects the Retina against Autoimmune Uveitis

by Raela B. Ridley, Brianna M. Young, Jieun Lee, Erin Walsh, Chulbul M. Ahmed, Alfred S. Lewin and Cristhian J. Ildefonso

J. Clin. Med. 2019, 8(12), 2082; https://doi.org/10.3390/jcm8122082 - 29 Nov 2019

Cited by 5 | Viewed by 4629

Abstract

Uveoretinitis is an ocular autoimmune disease caused by the activation of autoreactive T- cells targeting retinal antigens. The myxoma M013 gene is known to block NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) and inflammasome activation, and its gene delivery has been demonstrated [...] Read more.

Uveoretinitis is an ocular autoimmune disease caused by the activation of autoreactive T- cells targeting retinal antigens. The myxoma M013 gene is known to block NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) and inflammasome activation, and its gene delivery has been demonstrated to protect the retina against lipopolysaccharide (LPS)-induced uveitis. In this report we tested the efficacy of M013 in an experimental autoimmune uveoretinitis (EAU) mouse model. B10RIII mice were injected intravitreally with AAV (adeno associated virus) vectors delivering either secreted GFP (sGFP) or sGFP-TatM013. Mice were immunized with interphotorecptor retinoid binding protein residues 161–180 (IRBP_161–180) peptide in complete Freund’s adjuvant a month later. Mice were evaluated by fundoscopy and spectral domain optical coherence tomography (SD-OCT) at 14 days post immunization. Eyes were evaluated by histology and retina gene expression changes were measured by reverse transcribed quantitative PCR (RT-qPCR). No significant difference in ERG or retina layer thickness was observed between sGFP and sGFP-TatM013 treated non-uveitic mice, indicating safety of the vector. In EAU mice, expression of sGFP-TatM013 strongly lowered the clinical score and number of infiltrative cells within the vitreous humor when compared to sGFP treated eyes. Retina structure was protected, and pro-inflammatory genes expression was significantly decreased. These results indicate that gene delivery of myxoma M013 could be of clinical benefit against autoimmune diseases. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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17 pages, 3974 KiB

Open AccessArticle

A Virus-Derived Immune Modulating Serpin Accelerates Wound Closure with Improved Collagen Remodeling

by Liqiang Zhang, Jordan R. Yaron, Amanda M. Tafoya, Sarah E. Wallace, Jacquelyn Kilbourne, Shelley Haydel, Kaushal Rege, Grant McFadden and Alexandra R. Lucas

J. Clin. Med. 2019, 8(10), 1626; https://doi.org/10.3390/jcm8101626 - 4 Oct 2019

Cited by 22 | Viewed by 5351

Abstract

Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases [...] Read more.

Numerous treatments have been developed to promote wound healing based on current understandings of the healing process. Hemorrhaging, clotting, and associated inflammation regulate early wound healing. We investigated treatment with a virus-derived immune modulating serine protease inhibitor (SERPIN), Serp-1, which inhibits thrombolytic proteases and inflammation, in a mouse excisional wound model. Saline or recombinant Serp-1 were applied directly to wounds as single doses of 1 μg or 2 µg or as two 1 µg boluses. A chitosan-collagen hydrogel was also tested for Serp-1 delivery. Wound size was measured daily for 15 days and scarring assessed by Masson’s trichrome, Herovici’s staining, and immune cell dynamics and angiogenesis by immunohistochemistry. Serp-1 treatment significantly accelerated wound healing, but was blocked by urokinase-type plasminogen activator (uPAR) antibody. Repeated dosing at a lower concentration was more effective than single high-dose serpin. A single application of Serp-1-loaded chitosan-collagen hydrogel was as effective as repeated aqueous Serp-1 dosing. Serp-1 treatment of wounds increased arginase-1-expressing M2-polarized macrophage counts and periwound angiogenesis in the wound bed. Collagen staining also demonstrated that Serp-1 improves collagen maturation and organization at the wound site. Serp-1 has potential as a safe and effective immune modulating treatment that targets thrombolytic proteases, accelerating healing and reducing scar in deep cutaneous wounds. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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16 pages, 3786 KiB

Open AccessArticle

Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice

by Ahmed S. Elshikha, Georges Abboud, Lonneke van der Meijden-Erkelens, Yuanqing Lu, Mong-Jen Chen, Ye Yuan, Godelieva Ponjee, Leilani Zeumer, Minoru Satoh, Laurence Morel and Sihong Song

J. Clin. Med. 2019, 8(9), 1341; https://doi.org/10.3390/jcm8091341 - 29 Aug 2019

Cited by 8 | Viewed by 4028

Abstract

Diffuse alveolar hemorrhage (DAH) is a fatal complication in patients with lupus. DAH can be induced in B6 mice by an intraperitoneal injection of pristane. Since human alpha-1-antitrypsin (hAAT) is an anti-inflammatory and immuno-regulatory protein, we investigated the protective effect of hAAT against [...] Read more.

Diffuse alveolar hemorrhage (DAH) is a fatal complication in patients with lupus. DAH can be induced in B6 mice by an intraperitoneal injection of pristane. Since human alpha-1-antitrypsin (hAAT) is an anti-inflammatory and immuno-regulatory protein, we investigated the protective effect of hAAT against pristane-induced DAH in B6 mice and hAAT transgenic (hAAT-Tg) mice. We first showed that hAAT Tg expression lowers TNF-α production in B cells, as well as CD4+ T cells in untreated mice. Conversely, the frequency of regulatory CD4+CD25+ and CD4+CD25-IL-10+ cells was significantly higher in hAAT-Tg than in B6 mice. This confirmed the anti-inflammatory effect of hAAT that was observed even at steady state. One week after a pristane injection, the frequency of peritoneal Ly6C^hi inflammatory monocytes and neutrophils in hAAT-Tg mice was significantly lower than that in B6 mice. Importantly, pristane-induced DAH was completely prevented in hAAT-Tg mice and this was associated with a modulation of anti- to pro-inflammatory myeloid cell ratio/balance. We also showed that treatment with hAAT decreased the severity of DAH in B6 mice. These results showed for the first time that hAAT has a therapeutic potential for the treatment of DAH. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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11 pages, 6869 KiB

Open AccessArticle

Regulated hAAT Expression from a Novel rAAV Vector and Its Application in the Prevention of Type 1 Diabetes

by Hongxia Ma, Yuanqing Lu, Keith Lowe, Lonneke van der Meijden-Erkelens, Clive Wasserfall, Mark A. Atkinson and Sihong Song

J. Clin. Med. 2019, 8(9), 1321; https://doi.org/10.3390/jcm8091321 - 28 Aug 2019

Cited by 11 | Viewed by 3791

Abstract

We, and others, have previously achieved high and sustained levels of transgene expression from viral vectors, such as recombinant adeno-associated virus (rAAV). However, regulatable transgene expression may be preferred in gene therapy for diseases, such as type 1 diabetes (T1D) and rheumatoid arthritis [...] Read more.

We, and others, have previously achieved high and sustained levels of transgene expression from viral vectors, such as recombinant adeno-associated virus (rAAV). However, regulatable transgene expression may be preferred in gene therapy for diseases, such as type 1 diabetes (T1D) and rheumatoid arthritis (RA), in which the timing and dosing of the therapeutic gene product play critical roles. In the present study, we generated a positive feedback regulation system for human alpha 1 antitrypsin (hAAT) expression in the rAAV vector. We performed quantitative kinetics studies in vitro and in vivo demonstrating that this vector system can mediate high levels of inducible transgene expression. Transgene induction could be tailored to occur rapidly or gradually, depending on the dose of the inducing drug, doxycycline (Dox). Conversely, after withdrawal of Dox, the silencing of transgene expression occurred slowly over the course of several weeks. Importantly, rAAV delivery of inducible hAAT significantly prevented T1D development in non-obese diabetic (NOD) mice. These results indicate that this Dox-inducible vector system may facilitate the fine-tuning of transgene expression, particularly for hAAT treatment of human autoimmune diseases, including T1D. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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15 pages, 2199 KiB

Open AccessArticle

Peptide Antagonists for P-selectin Discriminate between Sulfatide-Dependent Platelet Aggregation and PSGL-1-Mediated Cell Adhesion

by Suzanne J.A. Korporaal, Tom J.M. Molenaar, Bianca C.H. Lutters, Illiana Meurs, Sandra Drost-Verhoef, Johan Kuiper, Theo J.C. van Berkel and Erik A.L. Biessen

J. Clin. Med. 2019, 8(8), 1266; https://doi.org/10.3390/jcm8081266 - 20 Aug 2019

Cited by 6 | Viewed by 3881

Abstract

Background: Membrane-exposed sulfatides are proposed to contribute to P-selectin-dependent platelet aggregation. Here, we demonstrated that P-selectin-mediated platelet aggregation on a collagen-coated surface under flow indeed depended on sulfatides and that this interaction differed considerably from the interaction of P-selectin with P-selectin Glycoprotein Ligand-1 [...] Read more.

Background: Membrane-exposed sulfatides are proposed to contribute to P-selectin-dependent platelet aggregation. Here, we demonstrated that P-selectin-mediated platelet aggregation on a collagen-coated surface under flow indeed depended on sulfatides and that this interaction differed considerably from the interaction of P-selectin with P-selectin Glycoprotein Ligand-1 (PSGL-1), which underlies leukocyte-endothelium adhesion. Methods and Results: Upon platelet activation, sulfatides were translocated to the platelet surface to form focal hot-spots. Interestingly, P-selectin was observed to exclusively interact with liposomes with a sulfatide density higher than 21% (w/w), indicating that the binding profile of P-selectin for sulfatide-rich liposomes was dependent on sulfatide density. Sulfatide-liposome binding to P-selectin and sulfatide/P-selectin-dependent platelet aggregation was blunted by peptide antagonists, carrying the EWVDV motif within N-terminal extensions, such as CDVEWVDVSC (half maximal inhibitory concentration IC₅₀ = 0.2 μM), but not by the EWVDV core motif itself (IC₅₀ > 1000 μM), albeit both being equally potent inhibitors of PSGL-1/P-selectin interaction (IC₅₀= 7–12 μM). Conclusions: Our data suggest that the sulfatide/P-selectin interaction implicates multiple binding pockets, which only partly overlap with that of PSGL-1. These observations open ways to selectively interfere with sulfatide/P-selectin-dependent platelet aggregation without affecting PSGL-1-dependent cell adhesion. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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Review

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30 pages, 2575 KiB

Open AccessReview

Deriving Immune Modulating Drugs from Viruses—A New Class of Biologics

by Jordan R. Yaron, Liqiang Zhang, Qiuyun Guo, Michelle Burgin, Lauren N. Schutz, Enkidia Awo, Lyn Wise, Kurt L. Krause, Cristhian J. Ildefonso, Jacek M. Kwiecien, Michael Juby, Masmudur M. Rahman, Hao Chen, Richard W. Moyer, Antonio Alcami, Grant McFadden and Alexandra R. Lucas

J. Clin. Med. 2020, 9(4), 972; https://doi.org/10.3390/jcm9040972 - 31 Mar 2020

Cited by 18 | Viewed by 6944

Abstract

Viruses are widely used as a platform for the production of therapeutics. Vaccines containing live, dead and components of viruses, gene therapy vectors and oncolytic viruses are key examples of clinically-approved therapeutic uses for viruses. Despite this, the use of virus-derived proteins as [...] Read more.

Viruses are widely used as a platform for the production of therapeutics. Vaccines containing live, dead and components of viruses, gene therapy vectors and oncolytic viruses are key examples of clinically-approved therapeutic uses for viruses. Despite this, the use of virus-derived proteins as natural sources for immune modulators remains in the early stages of development. Viruses have evolved complex, highly effective approaches for immune evasion. Originally developed for protection against host immune responses, viral immune-modulating proteins are extraordinarily potent, often functioning at picomolar concentrations. These complex viral intracellular parasites have “performed the R&D”, developing highly effective immune evasive strategies over millions of years. These proteins provide a new and natural source for immune-modulating therapeutics, similar in many ways to penicillin being developed from mold or streptokinase from bacteria. Virus-derived serine proteinase inhibitors (serpins), chemokine modulating proteins, complement control, inflammasome inhibition, growth factors (e.g., viral vascular endothelial growth factor) and cytokine mimics (e.g., viral interleukin 10) and/or inhibitors (e.g., tumor necrosis factor) have now been identified that target central immunological response pathways. We review here current development of virus-derived immune-modulating biologics with efficacy demonstrated in pre-clinical or clinical studies, focusing on pox and herpesviruses-derived immune-modulating therapeutics. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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16 pages, 571 KiB

Open AccessReview

Oncolytic Virotherapy with Myxoma Virus

by Masmudur M. Rahman and Grant McFadden

J. Clin. Med. 2020, 9(1), 171; https://doi.org/10.3390/jcm9010171 - 8 Jan 2020

Cited by 59 | Viewed by 6288

Abstract

Oncolytic viruses are one of the most promising novel therapeutics for malignant cancers. They selectively infect and kill cancer cells while sparing the normal counterparts, expose cancer- specific antigens and activate the host immune system against both viral and tumor determinants. Oncolytic viruses [...] Read more.

Oncolytic viruses are one of the most promising novel therapeutics for malignant cancers. They selectively infect and kill cancer cells while sparing the normal counterparts, expose cancer- specific antigens and activate the host immune system against both viral and tumor determinants. Oncolytic viruses can be used as monotherapy or combined with existing cancer therapies to become more potent. Among the many types of oncolytic viruses that have been developed thus far, members of poxviruses are the most promising candidates against diverse cancer types. This review summarizes recent advances that are made with oncolytic myxoma virus (MYXV), a member of the Leporipoxvirus genus. Unlike other oncolytic viruses, MYXV infects only rabbits in nature and causes no harm to humans or any other non-leporid animals. However, MYXV can selectively infect and kill cancer cells originating from human, mouse and other host species. This selective cancer tropism and safety profile have led to the testing of MYXV in various types of preclinical cancer models. The next stage will be successful GMP manufacturing and clinical trials that will bring MYXV from bench to bedside for the treatment of currently intractable malignancies. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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16 pages, 5718 KiB

Open AccessReview

Early Nuclear Events after Herpesviral Infection

by Florian Full and Armin Ensser

J. Clin. Med. 2019, 8(9), 1408; https://doi.org/10.3390/jcm8091408 - 7 Sep 2019

Cited by 24 | Viewed by 5870

Abstract

Herpesviruses are important pathogens that can cause significant morbidity and mortality in the human population. Herpesviruses have a double-stranded DNA genome, and viral genome replication takes place inside the nucleus. Upon entering the nucleus, herpesviruses have to overcome the obstacle of cellular proteins [...] Read more.

Herpesviruses are important pathogens that can cause significant morbidity and mortality in the human population. Herpesviruses have a double-stranded DNA genome, and viral genome replication takes place inside the nucleus. Upon entering the nucleus, herpesviruses have to overcome the obstacle of cellular proteins in order to enable viral gene expression and genome replication. In this review, we want to highlight cellular proteins that sense incoming viral genomes of the DNA-damage repair (DDR) pathway and of PML-nuclear bodies (PML-NBs) that all can act as antiviral restriction factors within the first hours after the viral genome is released into the nucleus. We show the function and significance of both nuclear DNA sensors, the DDR and PML-NBs, and demonstrate for three human herpesviruses of the alpha-, beta- and gamma-subfamilies, HSV-1, HCMV and KSHV respectively, how viral tegument proteins antagonize these pathways. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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14 pages, 998 KiB

Open AccessReview

Immunoproteomic Lessons for Human Respiratory Syncytial Virus Vaccine Design

by Daniel López, Alejandro Barriga, Elena Lorente and Carmen Mir

J. Clin. Med. 2019, 8(4), 486; https://doi.org/10.3390/jcm8040486 - 10 Apr 2019

Cited by 2 | Viewed by 3197

Abstract

Accurate antiviral humoral and cellular immune responses require prior recognition of antigenic peptides presented by human leukocyte antigen (HLA) class I and II molecules on the surface of antigen-presenting cells. Both the helper and the cytotoxic immune responses are critical for the control [...] Read more.

Accurate antiviral humoral and cellular immune responses require prior recognition of antigenic peptides presented by human leukocyte antigen (HLA) class I and II molecules on the surface of antigen-presenting cells. Both the helper and the cytotoxic immune responses are critical for the control and the clearance of human respiratory syncytial virus (HRSV) infection, which is a significant cause of morbidity and mortality in infected pediatric, immunocompromised and elderly populations. In this article we review the immunoproteomics studies which have defined the general antigen processing and presentation rules that determine both the immunoprevalence and the immunodominance of the cellular immune response to HRSV. Mass spectrometry and functional analyses have shown that the HLA class I and II cellular immune responses against HRSV are mainly focused on three viral proteins: fusion, matrix, and nucleoprotein. Thus, these studies have important implications for vaccine development against this virus, since a vaccine construct including these three relevant HRSV proteins could efficiently stimulate the major components of the adaptive immune system: humoral, helper, and cytotoxic effector immune responses. Full article

(This article belongs to the Special Issue Inflammatory Diseases and Viral Immune Modulating Protein Therapeutics)

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