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1.
Sci Adv ; 7(45): eabj0611, 2021 11 05.
Article in English | MEDLINE | ID: covidwho-1515256

ABSTRACT

This work reports a suction-based cutaneous delivery method for in vivo DNA transfection. Following intradermal Mantoux injection of plasmid DNA in a rat model, a moderate negative pressure is applied to the injection site, a technique similar to Chinese báguàn and Middle Eastern hijama cupping therapies. Strong GFP expression was demonstrated with pEGFP-N1 plasmids where fluorescence was observed as early as 1 hour after dosing. Modeling indicates a strong correlation between focal strain/stress and expression patterns. The absence of visible and/or histological tissue injury contrasts with current in vivo transfection systems such as electroporation. Specific utility was demonstrated with a synthetic SARS-CoV-2 DNA vaccine, which generated host humoral immune response in rats with notable antibody production. This method enables an easy-to-use, cost-effective, and highly scalable platform for both laboratorial transfection needs and clinical applications for nucleic acid­based therapeutics and vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , DNA , SARS-CoV-2 , Skin/immunology , Transfection , Vaccines, DNA , Administration, Cutaneous , Animals , COVID-19/genetics , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , DNA/genetics , DNA/immunology , DNA/pharmacology , Male , Rats , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Suction , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Vaccines, DNA/pharmacology
2.
Life Sci Alliance ; 4(11)2021 11.
Article in English | MEDLINE | ID: covidwho-1404295

ABSTRACT

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.


Subject(s)
Antibodies, Antinuclear/immunology , Autoantibodies/immunology , COVID-19/immunology , COVID-19/metabolism , Adult , Aged , Aged, 80 and over , Antibodies, Antinuclear/blood , Autoantibodies/blood , Biomarkers , DNA/chemistry , DNA/immunology , Erythrocytes/immunology , Female , Humans , Male , Middle Aged , Phosphatidylserines/immunology , Prognosis , Retrospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index
3.
Chem Biol Interact ; 344: 109497, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1312959

ABSTRACT

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Exosomes/immunology , Plasma/immunology , Adaptive Immunity/immunology , Antibodies/immunology , Antigens/immunology , DNA/immunology , Humans , Immunization, Passive , RNA/immunology , SARS-CoV-2/immunology
4.
Chem Biol Interact ; 344: 109497, 2021 Aug 01.
Article in English | MEDLINE | ID: covidwho-1309180

ABSTRACT

Extracellular vesicles like exosomes are important therapeutic tactics for treating COVID -19. By utilizing convalescent plasma derived exosomes (CPExo) from COVID-19 recovered persistence could accelerate the treatment strategies in the current state of affairs. Adequate literature has shown that administering the exosome to the in vivo system could be beneficial and could target the pathogens in an effective and precise manner. In this hypothesis we highlight the CPExo instead of convalescent plasma (CP), perhaps to dispense of exosomes are gratified and it's more effectively acquired immune response conferral through antibodies. COVID-19 convalescent plasma has billions of exosomes and it has aptitudes to carry molecular constituents like proteins, lipids, RNA and DNA, etc. Moreover, exosomes are capable of recognizing antigens with adequate sensitivity and specificity. Many of these derivatives could trigger an immune modulation into the cells and act as an epigenetic inheritor response to target pathogens through RNAs. COIVID-19 resistance activated plasma-derived exosomes are either responsible for the effects of plasma beyond the contained immune antibodies or could be inhibitory. The proposed hypothesis suggests that preselecting the plasma-derived antibodies and RNAs merged exosomes would be an optimized therapeutic tactic for COVID-19 patients. We suggest that, the CPExo has a multi-potential effect for treatment efficacy by acting as immunotherapeutic, drug carrier, and diagnostic target with noncoding genetic materials as a biomarker.


Subject(s)
COVID-19/immunology , COVID-19/therapy , Exosomes/immunology , Plasma/immunology , Adaptive Immunity/immunology , Antibodies/immunology , Antigens/immunology , DNA/immunology , Humans , Immunization, Passive , RNA/immunology , SARS-CoV-2/immunology
6.
Emerg Microbes Infect ; 10(1): 342-355, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1069193

ABSTRACT

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center B cell development, which is critical for high-affinity memory B cell responses, the DNA and protein co-delivery vaccine approach has great potential to serve as a safe and effective approach to develop COVID-19 vaccines that provide long-term protection.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/immunology , Vaccines, Subunit/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Cell Line , DNA/immunology , HEK293 Cells , Humans , Lymphocyte Count , Macaca mulatta , Mice , Mice, Inbred C57BL , Plasmids/genetics , Rabbits , Recombinant Proteins/immunology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , T-Lymphocytes/immunology
7.
Clin Rheumatol ; 39(9): 2811-2815, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-679749

ABSTRACT

In the midst of the COVID-19 pandemic, further understanding of its complications points towards dysregulated immune response as a major component. Systemic lupus erythematosus (SLE) is also a disease of immune dysregulation leading to multisystem compromise. We present a case of new-onset SLE concomitantly with COVID-19 and development of antiphospholipid antibodies. An 18-year-old female that presented with hemodynamic collapse and respiratory failure, progressed to cardiac arrest, and had a pericardial tamponade drained. She then progressed to severe acute respiratory distress syndrome, severe ventricular dysfunction, and worsening renal function with proteinuria and hematuria. Further studies showed bilateral pleural effusions, positive antinuclear and antidouble-stranded DNA antibodies, lupus anticoagulant, and anticardiolipin B. C3 and C4 levels were low. SARS-Cov-2 PCR was positive after 2 negative tests. She also developed multiple deep venous thrombosis, in the setting of positive antiphospholipid antibodies and lupus anticoagulant. In terms of pathophysiology, COVID-19 is believed to cause a dysregulated cytokine response which could potentially be exacerbated by the shift in Th1 to Th2 response seen in SLE. Also, it is well documented that viral infections are an environmental factor that contributes to the development of autoimmunity; however, COVID-19 is a new entity, and it is not known if it could trigger autoimmune conditions. Additionally, it is possible that SARS-CoV-2, as it happens with other viruses, might lead to the formation of antiphospholipid antibodies, potentially contributing to the increased rates of thrombosis seen in COVID-19.


Subject(s)
Antiphospholipid Syndrome/immunology , Coronavirus Infections/immunology , Lupus Erythematosus, Systemic/immunology , Pneumonia, Viral/immunology , Adolescent , Anemia/etiology , Antibodies, Anticardiolipin/immunology , Antibodies, Antinuclear/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/therapy , Anuria/etiology , Betacoronavirus , COVID-19 , Cardiac Tamponade/diagnostic imaging , Cardiac Tamponade/etiology , Cardiac Tamponade/therapy , Complement C3/immunology , Complement C4/immunology , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/therapy , DNA/immunology , Echocardiography , Fatal Outcome , Female , Heart Arrest/etiology , Hematuria/etiology , Humans , Lupus Coagulation Inhibitor/immunology , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Pandemics , Patient Positioning , Pericardiocentesis , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/therapy , Prone Position , Proteinuria/etiology , Renal Dialysis , Renal Insufficiency/etiology , Renal Insufficiency/therapy , Respiration, Artificial , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , SARS-CoV-2 , Thrombocytopenia/etiology , Venous Thrombosis/etiology , Ventricular Dysfunction, Left/diagnostic imaging
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