Innate immune-mediated antiviral response to SARS-CoV-2 and convalescent sera a potential prophylactic and therapeutic agent to tackle COVID-19

ABSTRACT The whole world is confronting the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Unfortunately, there is no vaccine to prevent novel coronavirus infection. Besides several experimental drugs, the strong immune responses and convalescent sera are the current two potential options to tackle coronavirus disease 2019 (COVID-19) infection. Innate immune-mediated antiviral responses are initiated by the recognition of viral invasion through pathogen-associated molecular patterns (PAMPs). In coronavirus, the PAMPs are recognized by Toll-like receptors 3 and 7, endosomal ribonucleic acid receptors, RNA in cytosol, and by pattern recognition receptor (RIG-1) in the alveolar cells and site of invasion. Nuclear factor-κB and interferon regulatory transcription factor (IRF3) are activated in response to the above recognition episode and translocate to nucleus. These transcription factors in the nucleus initiate the expression of interferon type 1 and pro-inflammatory cytokine storm, which leads to first line of defense at the site of viral entrance. The effectiveness of innate immune system is greatly relies on type 1 interferons and its cascade, because of their role in the inhibition of viral replication and initiation of adaptive immune responses. The successful interferon type 1 response put down the viral replication and transmission at prompt point. Passive immunization is the administering of antibodies into infected patients, which is taken from recovered individuals. The convalescent sera of the recovered COVID-19 patients are containing antiviral neutralizing antibodies and are used therapeutically for infected individuals by SARS-CoV-2 and for the purpose of prophylaxis in exposed individuals. The convalescent sera is found effective when administered early at the onset of symptoms.

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Innate Immune-mediated Antiviral Response to SARS-CoV-2 and Convalescent sera a potential Prophylactic and Therapeutic Agent to Tackle COVID-19 (Preprint)

10.2196/preprints.21091 ◽

2020 ◽

Author(s):

Abdullah Abdullah ◽

Shah Faisal

Keyword(s):

Immune System ◽

Immune Responses ◽

Viral Replication ◽

Innate Immune System ◽

Passive Immunization ◽

Innate Immune ◽

Alveolar Cells ◽

Experimental Drugs ◽

Immune Mediated

UNSTRUCTURED The whole world is confronting the pandemic of SARS-CoV-2. And unfortunately there is no vaccine to prevent from novel coronavirus infection. Beside several experimental drugs, the strong immune responses and convalescent sera are the current two potential options to tackle COVID-19 infection. When the virus get enter into the lungs the innate immune system activated. Innate immune-mediated antiviral responses is initiated by the recognition of viral invasion through PAMPs. In coronavirus the pathogen associated molecular patterns are recognized by toll like receptors (TLR-3 & 7), endosomal ribonucleic acid receptors, RNA in cytosol and by pattern recognition receptor (PRR RIG-1) in the alveolar cells and site of invasion. Nuclear factor (NF-κB) and interferon regulatory transcription factor (IRF3) are activated in response to above recognition episode and translocate to nucleus. These transcription factors in the nucleus initiate the expression of interferon type 1 and pro-inflammatory cytokine storm, which leads to first line of defense at site of viral entrance. The effectiveness of innate immune system greatly relies on type 1 interferon’s and its cascade, because of their role in inhibition of viral replication and initiation of adaptive immune responses. The successful interferon type 1 response put down the viral replication and transmission at prompt point. Passive immunization is the administering of antibodies into infected patients which is taken from recovered individuals. The convalescent sera of the recovered COVID-19 patients contains antiviral neutralizing antibodies and used for the purpose of prophylaxis in exposed and therapeutically in infected individuals by SARS-CoV-2. The convalescent sera is found effective when administered early at the onset of symptoms.

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Innate immune responses and type 1 diabetes: A role for a long non-coding RNA?

Diabetologie und Stoffwechsel ◽

10.1055/s-0034-1374906 ◽

2014 ◽

Vol 9 (S 01) ◽

Author(s):

MP Ashton ◽

I Tan ◽

L Mackin ◽

C Elso ◽

E Chu ◽

...

Keyword(s):

Type 1 Diabetes ◽

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Non Coding Rna ◽

Long Non Coding Rna

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DNA Vaccination with the Human Immunodeficiency Virus Type 1 SF162ΔV2 Envelope Elicits Immune Responses That Offer Partial Protection from Simian/Human Immunodeficiency Virus Infection to CD8+ T-Cell-Depleted Rhesus Macaques

Journal of Virology ◽

10.1128/jvi.75.3.1547-1550.2001 ◽

2001 ◽

Vol 75 (3) ◽

pp. 1547-1550 ◽

Cited By ~ 70

Author(s):

S. Cherpelis ◽

I. Shrivastava ◽

A. Gettie ◽

X. Jin ◽

D. D. Ho ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Rhesus Macaques ◽

Cd8 T Cell ◽

Dna Immunization ◽

Plasma Virus ◽

Partial Protection ◽

Immunodeficiency Virus

ABSTRACT DNA immunization of macaques with the SF162ΔV2 envelope elicited lymphoproliferative responses and potent neutralizing antibodies. The animals were depleted of their CD8+ T lymphocytes and then challenged intravenously with SHIV162P4. Compared to unvaccinated animals, the vaccinated macaques had lower peak viremia levels, rapidly cleared plasma virus, and showed delayed seroconversion.

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The role of type 1 interferons in Gram-negative bacteria-induced coagulation

Blood ◽

10.1182/blood.2019002282 ◽

2020 ◽

Cited By ~ 4

Author(s):

Xinyu Yang ◽

Xiaoye Cheng ◽

Yiting Tang ◽

Xianhui Qiu ◽

Zhongtai Wang ◽

...

Keyword(s):

Immune Responses ◽

Bacterial Infection ◽

Innate Immune ◽

Coagulation Cascade ◽

Outer Cell ◽

Gram Negative Bacteria ◽

Innate Immune Responses ◽

Gram Negative ◽

Type 1 Interferons

Bacterial infection not only stimulates innate immune responses but also activates the coagulation cascades. Over-activation of the coagulation system in bacterial sepsis leads to disseminated intravascular coagulation (DIC), a life-threatening condition. However, the mechanisms by which bacterial infection activates the coagulation cascade are not fully understood. Here we show that type 1 interferons (IFNs), widely expressed family of cytokines that orchestrate innate antiviral and antibacterial immunity, mediate bacterial infection-induced DIC through amplifying the release of high mobility box group box 1 (HMGB1) into the blood stream. Inhibition of the expression of type 1 IFNs, disruption of their receptor IFN-α/βR or downstream effector (e.g., HMGB1) uniformly decreased Gram-negative bacteria-induced DIC. Mechanistically, extracellular HMGB1 markedly increased the pro-coagulant activity of tissue factor (TF) by promoting the externalization of phosphatidylserine (PS) to the outer cell surface, where PS assembles a complex of cofactor-proteases of the coagulation cascades. These findings not only provide novel insights into the link between innate immune responses and coagulation, but also open a new avenue for developing novel therapeutic strategies to prevent DIC in sepsis.

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A Single Injection of Recombinant Measles Virus Vaccines Expressing Human Immunodeficiency Virus (HIV) Type 1 Clade B Envelope Glycoproteins Induces Neutralizing Antibodies and Cellular Immune Responses to HIV

Journal of Virology ◽

10.1128/jvi.78.1.146-157.2004 ◽

2004 ◽

Vol 78 (1) ◽

pp. 146-157 ◽

Cited By ~ 97

Author(s):

Clarisse Lorin ◽

Lucile Mollet ◽

Frédéric Delebecque ◽

Chantal Combredet ◽

Bruno Hurtrel ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Measles Virus ◽

Single Injection ◽

Protein A ◽

V3 Loop ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT The anchored and secreted forms of the human immunodeficiency virus type 1 (HIV-1) 89.6 envelope glycoprotein, either complete or after deletion of the V3 loop, were expressed in a cloned attenuated measles virus (MV) vector. The recombinant viruses grew as efficiently as the parental virus and expressed high levels of the HIV protein. Expression was stable during serial passages. The immunogenicity of these recombinant vectors was tested in mice susceptible to MV and in macaques. High titers of antibodies to both MV and HIV-Env were obtained after a single injection in susceptible mice. These antibodies neutralized homologous SHIV89.6p virus, as well as several heterologous HIV-1 primary isolates. A gp160 mutant in which the V3 loop was deleted induced antibodies that neutralized heterologous viruses more efficiently than antibodies induced by the native envelope protein. A high level of CD8+ and CD4+ cells specific for HIV gp120 was also detected in MV-susceptible mice. Furthermore, recombinant MV was able to raise immune responses against HIV in mice and macaques with a preexisting anti-MV immunity. Therefore, recombinant MV vaccines inducing anti-HIV neutralizing antibodies and specific T lymphocytes responses deserve to be tested as a candidate AIDS vaccine.

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Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes

Journal of Experimental Medicine ◽

10.1084/jem.20111843 ◽

2012 ◽

Vol 210 (1) ◽

pp. 191-203 ◽

Cited By ~ 51

Author(s):

Qibin Zhang ◽

Thomas L. Fillmore ◽

Athena A. Schepmoes ◽

Therese R.W. Clauss ◽

Marina A. Gritsenko ◽

...

Keyword(s):

Type 1 Diabetes ◽

Immune Responses ◽

Innate Immune ◽

Healthy Controls ◽

Innate Immune Responses ◽

C1 Inhibitor ◽

Serum Samples ◽

Healthy Control

Using global liquid chromatography-mass spectrometry (LC-MS)–based proteomics analyses, we identified 24 serum proteins that were significantly variant between those with type 1 diabetes (T1D) and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses, and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins, with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects. 16 peptides were verified as having very good discriminating power, with areas under the receiver operating characteristic curve ≥0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetics) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using sera from 50 age-matched type 2 diabetic individuals, and a subset of proteins, C1 inhibitor in particular, were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with T1D from healthy controls and those with type 2 diabetes suggests that dysregulated innate immune responses may be associated with the development of this disorder.

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“Corneal Nerves, CD11c+ Dendritic Cells and Their Impact on Ocular Immune Privilege”

Frontiers in Immunology ◽

10.3389/fimmu.2021.701935 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jerry Y. Niederkorn

Keyword(s):

Immune Responses ◽

Inflammatory Diseases ◽

Innate Immune ◽

Immune Privilege ◽

Innate Immune Responses ◽

Regulatory Processes ◽

Immune Mediated ◽

Corneal Nerves ◽

The Central Nervous System ◽

The Brain

The eye and the brain have limited capacities for regeneration and as such, immune-mediated inflammation can produce devastating consequences in the form of neurodegenerative diseases of the central nervous system or blindness as a result of ocular inflammatory diseases such as uveitis. Accordingly, both the eye and the brain are designed to limit immune responses and inflammation – a condition known as “immune privilege”. Immune privilege is sustained by physiological, anatomical, and regulatory processes that conspire to restrict both adaptive and innate immune responses.

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Perillaldehyde Inhibition of cGAS Reduces dsDNA-Induced Interferon Response

Frontiers in Immunology ◽

10.3389/fimmu.2021.655637 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lei Chu ◽

Chenhui Li ◽

Yongxing Li ◽

Qiuya Yu ◽

Huansha Yu ◽

...

Keyword(s):

Innate Immunity ◽

Herpes Simplex ◽

Immune Responses ◽

Therapeutic Benefit ◽

Perilla Frutescens ◽

Innate Immune ◽

Interferon Response ◽

Innate Immune Responses ◽

Simplex Virus

Cyclic GMP-AMP synthase (cGAS), serving as a primary sensor of intracellular DNA, is essential to initiate anti-microbial innate immunity. Inappropriate activation of cGAS by self-DNA promotes severe autoinflammatory diseases such as Aicardi–Goutières syndrome (AGS); thus, inhibition of cGAS may provide therapeutic benefit in anti-autoimmunity. Here we report that perillaldehyde (PAH), a natural monoterpenoid compound derived from Perilla frutescens, suppresses cytosolic-DNA-induced innate immune responses by inhibiting cGAS activity. Mice treated with PAH are more susceptible to herpes simplex virus type 1 (HSV-1) infection. Moreover, administration with PAH markedly ameliorates self-DNA-induced autoinflammatory responses in a mouse model of AGS. Collectively, our study reveals that PAH can effectively inhibit cGAS-STING signaling and could be developed toward the treatment of cGAS-mediated autoimmune diseases.

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Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization

10.1101/2020.11.06.372037 ◽

2020 ◽

Cited By ~ 3

Author(s):

Zhuoming Liu ◽

Laura A. VanBlargan ◽

Paul W. Rothlauf ◽

Louis-Marie Bloyet ◽

Rita E. Chen ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Serum Antibody ◽

Single Amino Acid ◽

Cross Resistance ◽

S Protein ◽

Mutational Landscape ◽

Immune Mediated ◽

Human Sera ◽

Escape Mutants

ABSTRACTAlthough neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of most COVID-19 vaccines and being developed as therapeutics, escape mutations could compromise such countermeasures. To define the immune-mediated mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor binding domain (RBD) to generate 48 escape mutants. These variants were mapped onto the RBD structure and evaluated for cross-resistance by convalescent human plasma. Although each mAb had unique resistance profiles, many shared residues within an epitope, as several variants were resistant to multiple mAbs. Remarkably, we identified mutants that escaped neutralization by convalescent human sera, suggesting that some humans induce a narrow repertoire of neutralizing antibodies. By comparing the antibody-mediated mutational landscape in S protein with sequence variation in circulating SARS-CoV-2 strains, we identified single amino acid substitutions that could attenuate neutralizing immune responses in some humans.

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Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239

Journal of Virology ◽

10.1128/jvi.00171-06 ◽

2006 ◽

Vol 80 (12) ◽

pp. 5875-5885 ◽

Cited By ~ 204

Author(s):

Nancy A. Wilson ◽

Jason Reed ◽

Gnankang S. Napoe ◽

Shari Piaskowski ◽

Andy Szymanski ◽

...

Keyword(s):

Immune Responses ◽

Viral Replication ◽

Simian Immunodeficiency Virus ◽

Neutralizing Antibodies ◽

Low Dose ◽

Chronic Phase ◽

Set Point ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Cellular Immune

ABSTRACT The goal of an AIDS vaccine regimen designed to induce cellular immune responses should be to reduce the viral set point and preserve memory CD4 lymphocytes. Here we investigated whether vaccine-induced cellular immunity in the absence of any Env-specific antibodies can control viral replication following multiple low-dose challenges with the highly pathogenic SIVmac239 isolate. Eight Mamu-A*01-positive Indian rhesus macaques were vaccinated with simian immunodeficiency virus (SIV) gag, tat, rev, and nef using a DNA prime-adenovirus boost strategy. Peak viremia (P = 0.007) and the chronic phase set point (P = 0.0192) were significantly decreased in the vaccinated cohort, out to 1 year postinfection. Loss of CD4+ memory populations was also ameliorated in vaccinated animals. Interestingly, only one of the eight vaccinees developed Env-specific neutralizing antibodies after infection. The control observed was significantly improved over that observed in animals vaccinated with SIV gag only. Vaccine-induced cellular immune responses can, therefore, exert a measure of control over replication of the AIDS virus in the complete absence of neutralizing antibody and give us hope that a vaccine designed to induce cellular immune responses might control viral replication.

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