scholarly journals Pitfalls at Chemistry of Adenoviral Vector Vaccine against COVID-19 and how to Circumvent It.

2021 ◽  
Author(s):  
Amr Kamel Khalil Ahmed ◽  
Abdullah Alkattan
Keyword(s):  
Liver Toxicity ◽  
Ethylenediaminetetraacetic Acid ◽  
Adenovirus Vector ◽  
Adenoviral Vectors ◽  
Lower Serum ◽  
Vector Vaccine ◽  
Chloride Hexahydrate ◽  
Zinc Chelator ◽  
Inactive Ingredients ◽  
First Time

ChAdOx1 nCoV-19 vaccine is an adenovirus vector vaccine that designed to provoke immunity against SARS-CoV-2.This vaccine contains several inactive ingredients, including sodium chloride, magnesium chloride hexahydrate, ethanol, sucrose, and Ethylenediaminetetraacetic acid (EDTA).EDTA is a very potent zinc chelator which is used commonly in protein interaction studies. Exposure to EDTA even in lower concentrations may cause extreme stripping of zinc from many proteins, in-cluding zinc-binding proteins that described as a component of the largest and most complex gene superfamily in metazoans and the most common class of transcription factors.the EDTA-induced thrombocytopenia is a risk phenomenon caused by EDTA-dependent anti-platelet auto-antibodies that identify antigens modified by EDTA.Another issue is the adenovirus in the vaccine. It can induce thrombocytopenia, a potentially serious complication of gene therapy protocols using this type of vector.PEGylation already induced significantly lower serum il-6 levels by 70% (14)We noted that the study by Katie et al studied immune response by a single dose of ChAdOx1 nCov-19 not included test of Il-6 (15)We conclude from previous studies that the PEGylating of adenoviral vectors can be promise tech-nology as safety profile as significantly reduced IL-6 and liver toxicity and how avoiding the pitfalls of chemistry and virology so the PEGylation since first time at 1999 introduced by O’Riordan,C.R et al (16) need more advancements

scholarly journals Pitfalls at Chemistry of Adenoviral Vector Vaccine against COVID-19 and how to Circumvent It.

2021 ◽  
Author(s):  
Amr Ahmed
Keyword(s):  
Gene Therapy ◽  
Adenoviral Vector ◽  
Liver Toxicity ◽  
Adenovirus Vector ◽  
Adenoviral Vectors ◽  
Zinc Binding ◽  
Lower Serum ◽  
Vector Vaccine ◽  
Zinc Chelator ◽  
First Time

ChAdOx1 nCoV-19 vaccine is an adenovirus vector vaccine that designed to provoke immunity against SARS-CoV-2. EDTA is a very potent zinc chelator which is used commonly in protein interaction studies. Exposure to EDTA even in lower concentrations may cause extreme stripping of zinc from many proteins, in-cluding zinc-binding proteins that described as a component of the largest and most complex gene superfamily in metazoans and the most common class of transcription factors. The zinc dissociation rates can vary greatly among these proteins. Another issue is the adenovirus in the vaccine. It can induce thrombocytopenia, a potentially serious complication of gene therapy protocols using this type of vector.PEGylation already induced significantly lower serum il-6 levels by 70% .We noted that the study by Katie et al studied immune response by a single dose of ChAdOx1 nCov-19 not included test of Il-6 (15)We conclude from previous studies that the PEGylating of adenoviral vectors can be promise tech-nology as safety profile as significantly reduced IL-6 and liver toxicity and how avoiding the pitfalls of chemistry and virology so the PEGylation since first time at 1999 introduced by O’Riordan,C.R et al (16) need more advancements

scholarly journals Prevention of influenza virus shedding and protection from lethal H1N1 challenge using a consensus 2009 H1N1 HA and NA adenovirus vector vaccine

Vaccine ◽  
2011 ◽  
Vol 29 (40) ◽  
pp. 7020-7026 ◽  
Author(s):  
Frank R. Jones ◽  
Elizabeth S. Gabitzsch ◽  
Younong Xu ◽  
Joseph P. Balint ◽  
Viktoriya Borisevich ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Adenovirus Vector ◽  
Virus Shedding ◽  
Vector Vaccine ◽  
2009 H1n1

scholarly journals Generation of an Adenovirus Vector Lacking E1, E2a, E3, and All of E4 except Open Reading Frame 3

1999 ◽  
Vol 73 (7) ◽  
pp. 6048-6055 ◽  
Author(s):  
Mario I. Gorziglia ◽  
Claudia Lapcevich ◽  
Soumitra Roy ◽  
Qiang Kang ◽  
Mike Kadan ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Liver Toxicity ◽  
Adenovirus Vector ◽  
Open Reading Frame ◽  
Reading Frame ◽  
Rous Sarcoma ◽  
Sarcoma Virus ◽  
Adenovirus Vectors ◽  
Virus Promoter

ABSTRACT Toxicity and immunity associated with adenovirus backbone gene expression is an important hurdle to overcome for successful gene therapy. Recent efforts to improve adenovirus vectors for in vivo use have focused on the sequential deletion of essential early genes. Adenovirus vectors have been constructed with the E1 gene deleted and with this deletion in combination with an E2a, E2b, or E4 deletion. We report here a novel vector (Av4orf3nBg) lacking E1, E2a, and all of E4 except open reading frame 3 (ORF3) and expressing a β-galactosidase reporter gene. This vector was generated by transfection of a plasmid carrying the full-length vector sequence into A30.S8 cells that express E1 and E2a but not E4. Production was subsequently performed in an E1-, E2a-, and E4-complementing cell line. We demonstrated with C57BL/6 mice that the Av4orf3nBg vector effected gene transfer with an efficiency comparable to that of the Av3nBg (wild-type E4) vector but that the former exhibited a higher level of β-galactosidase expression. This observation suggests that E4 ORF3 alone is able to enhance RNA levels from the β-galactosidase gene when the Rous sarcoma virus promoter is used to drive transgene expression in the mouse liver. In addition, we observed less liver toxicity in mice injected with the Av4orf3nBg vector than those injected with the Av3nBg vector at a comparable DNA copy number per cell. This study suggests that the additional deletion of E4 in an E1 and E2a deletion background may be beneficial in decreasing immunogenicity and improving safety and toxicity profiles, as well as increasing transgene capacity and expression for liver-directed gene therapy.

scholarly journals Clinical Case of the Occurrence of Stroke Followed by Death After Vaccine Against SARS-CoV-2

2021 ◽  
pp. 1-9
Author(s):  
Priciane Bárbara Ewerling Penna ◽  
◽  
Maria Cândida Moreno Penna ◽  
Douglas Domingues ◽  
Fernando Ferreira Penna Filho ◽  
...  
Keyword(s):  
Case Report ◽  
Brain Death ◽  
Brain Activity ◽  
Acute Infection ◽  
Adenovirus Vector ◽  
Rapid Progression ◽  
Vector Vaccine ◽  
Sagittal Sinus ◽  
Electrical Brain Activity ◽  
Hospital Emergency Room

Introduction: The current COVID-19 pandemic has involved developing vaccines to control the virulence of SARS-CoV-2. More than 4.1 million people have died from COVID-19.1 In response to this public health emergency, several vaccines against COVID-19 have been developed, with more than 3.7 billion doses administered worldwide. After the introduction of the adenovirus vector vaccine ChAdOx1, several cases of severe venous thrombosis with thrombocytopenia were reported worldwide. Objective: It was to present a case report of a 25-year-old female patient who presented extensive left intraparenchymal hematoma and rapid progression to brain death followed by death. Case report: A 25-year-old woman, CSS, was vaccinated against COVID-19 with the adenovirus ChAdOx1, 14 days after admission, evolved with a fever that started about 13 days ago, associated with holocranial, tight, moderate-intensity headache. On the day of admission, she was found by the torporous, unresponsive, and vomiting family, referred to the hospital emergency room. The patient was admitted to Glasgow 4 with evidence of anisocoria, with the left pupils larger than the right, rapidly progressing to mydriasis. Cranial computed tomography (CT) showed extensive left intraparenchymal hematoma, performing urgent decompressive craniectomy and placement of an intracranial pressure monitoring catheter. The cerebrospinal fluid exam did not show bacteria or fungi. CT angiography showed extensive thrombosis of the anterior portions of the superior sagittal sinus and probable thrombosis of the superficial drainage veins of the frontal regions. Skull CT revealed diffuse and bilateral ischemia. Laboratory tests showed mild thrombocytopenia and no change in the coagulogram. After one day, the patient evolved with worsening neurological status. Sedation was turned off to start the brain death protocol, which was confirmed twice. Finally, an electroencephalogram was performed with evidence of a straight-line tracing, without evidence of electrical brain activity. Final considerations: Several studies have been published regarding cerebral thrombosis, stroke, and thrombotic thrombocytopenic events. Thus, safe and effective vaccines against COVID-19 are an urgent need, as they can leave pathophysiological responses of hypercoagulability and thrombo inflammation associated with acute infection.

scholarly journals SARS-CoV-2 Vaccine-Induced Antibody Response and Reinfection in Persons with Past Natural Infection

2021 ◽  
Author(s):  
Nitu Chauhan ◽  
Ajeet Singh Chahar ◽  
Prem Singh ◽  
Neel Sarovar Bhavesh ◽  
Ravi Tandon ◽  
...  
Keyword(s):  
Viral Vector ◽  
Natural Infection ◽  
Previous History ◽  
Adenovirus Vector ◽  
Prior History ◽  
Igg Antibody ◽  
Vector Vaccine ◽  
Women Subjects ◽  
History Of ◽  
Antibody Titers

Several studies have shown that subjects with a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection had significantly higher antibody titers than previously uninfected vaccinees after vaccination with mRNA vaccine. Yet no information is available for other vaccines. In the current observational cohort study, 105 health care workers who had received Covishield an Adeno associated viral vector-based DNA vaccine were enrolled at Sarojini Nadu Medical College Agra, India. The study included 40 (23 men and 17 women) subjects with a previous history of SARS-CoV-2 infection and 65 participants (39 men and 26 women) who were not infected previously. Both the groups received the adenovirus vector vaccine ChAdOx1-S recombinant vaccines (Covishield, Astra Zeneca). The levels of SARS-CoV-2-anti-spike-IgG-antibodies titer were measured using Electrochemiluminescence immunoassay on Roche platform as arbitrary units per milliliter (AU/ml). After 28 days of the second dose, subjects with no previous SARSCoV-2 infection showed a significantly lower level of circulating anti-spike-IgG-antibody titers compared to previously infected participants. After the second dose, we also observed a significant increase in SARS-CoV-2 infection in subjects with no prior history of SARS-CoV-2 infection compared to subjects with a previous history of natural infection. The most important observation of the study is a low percentage of infection in previously infected subjects. The finding of the study also indicates the presence of robust humoral memory response in previously infected patients.

scholarly journals Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle

2015 ◽  
Vol 23 (2) ◽  
pp. 125-136 ◽  
Author(s):  
Gisselle N. Medina ◽  
Nestor Montiel ◽  
Fayna Diaz-San Segundo ◽  
Diego Sturza ◽  
Elizabeth Ramirez-Medina ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Clinical Signs ◽  
Foot And Mouth Disease ◽  
Adenovirus Vector ◽  
Human Adenovirus ◽  
Mouth Disease ◽  
Cell Mediated Immunity ◽  
Serum Samples ◽  
Vector Vaccine ◽  
Foot And Mouth

ABSTRACTNovel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4+and CD8+gamma interferon (IFN-γ)+cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle.

FeCl3•6H2O Catalysed Condensation of Aldehydes and Ketones in Ionic Liquid: A Novel Green Synthesis of Chalcones

2003 ◽  
Vol 2003 (1) ◽  
pp. 33-35 ◽  
Author(s):  
Xinying Zhang ◽  
Hongying Niu ◽  
Jianji Wang
Keyword(s):  
Ionic Liquid ◽  
Green Synthesis ◽  
Green Process ◽  
Reaction Conditions ◽  
Chloride Hexahydrate ◽  
Aldehydes And Ketones ◽  
First Time

Using iron(III) chloride hexahydrate as a catalyst, chalcones were efficiently prepared from acetophenone and benzaldehyde in ionic liquid (1-butyl-3-methylimidazolium tetrafluoroborate) for the first time. Compared with the known methods, this novel access to chalcones has the advantage of being a green process together with good yields and mild reaction conditions.

scholarly journals Readministration of Adenovirus Vector in Nonhuman Primate Lungs by Blockade of CD40-CD40 Ligand Interactions

2000 ◽  
Vol 74 (7) ◽  
pp. 3345-3352 ◽  
Author(s):  
Narendra Chirmule ◽  
Steven E. Raper ◽  
Linda Burkly ◽  
David Thomas ◽  
John Tazelaar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rhesus Monkeys ◽  
Neutralizing Antibodies ◽  
Interleukin 2 ◽  
Adenovirus Vector ◽  
Cd40 Ligand ◽  
Adenoviral Vectors ◽  
Immunoglobulin M ◽  
Long Term Effects ◽  
Activated T Cells

ABSTRACT The interaction between CD40 on B cells and CD40 ligand (CD40L) on activated T cells is important for B-cell differentiation in T-cell-dependent humoral responses. We have extended our previous murine studies of CD40-CD40L in adenoviral vector-mediated immune responses to rhesus monkeys. Primary immune responses to adenoviral vectors and the ability to readminister vector were studied in rhesus monkeys in the presence or absence of a transient treatment with a humanized anti-CD40 ligand antibody (hu5C8). Adult animals were treated with hu5C8 at the time vector was instilled into the lung. Immunological analyses demonstrated suppression of adenovirus-induced lymphoproliferation and cytokine responses (interleukin-2 [IL-2], gamma interferon, IL-4, and IL-10) in hu5C8-treated animals. Animals treated with hu5C8 secreted adenovirus-specific immunoglobulin M (IgM) levels comparable to control animals, but did not secrete IgA or develop neutralizing antibodies; consequently, the animals could be readministered with adenovirus vector expressing alkaline phosphatase. A second study was designed to examine the long-term effects on immune functions of a short course of hu5C8. Acute hu5C8 treatment resulted in significant and prolonged inhibition of the adenovirus-specific humoral response well beyond the time hu5C8 effects were no longer significant. These studies demonstrate the potential of hu5C8 as an immunomodulatory regimen to enable administration of adenoviral vectors, and they advocate testing this model in humans.

scholarly journals Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Samir Andrade Mendonça ◽  
Reka Lorincz ◽  
Paul Boucher ◽  
David T. Curiel
Keyword(s):  
Adenoviral Vector ◽  
New Technologies ◽  
Rapid Development ◽  
Vaccination Campaign ◽  
Adenoviral Vectors ◽  
Molecular Characteristics ◽  
Vector Vaccine ◽  
Vector Systems ◽  
The Impact ◽  
Full Consideration

AbstractAdenoviral vectors have been explored as vaccine agents for a range of infectious diseases, and their ability to induce a potent and balanced immune response made them logical candidates to apply to the COVID-19 pandemic. The unique molecular characteristics of these vectors enabled the rapid development of vaccines with advanced designs capable of overcoming the biological challenges faced by early adenoviral vector systems. These successes and the urgency of the COVID-19 situation have resulted in a flurry of candidate adenoviral vector vaccines for COVID-19 from both academia and industry. These vaccines represent some of the lead candidates currently supported by Operation Warp Speed and other government agencies for rapid translational development. This review details adenoviral vector COVID-19 vaccines currently in human clinical trials and provides an overview of the new technologies employed in their design. As these vaccines have formed a cornerstone of the COVID-19 global vaccination campaign, this review provides a full consideration of the impact and development of this emerging platform.

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