scholarly journals Stealth Adapted Coronaviruses Resulting from the Use of Covid-19 Vaccines

2021 ◽  
Author(s):  
W John Martin ◽  
W John Martin
Keyword(s):  
Cellular Immunity ◽  
Immune Evasion ◽  
Defense Mechanism ◽  
Natural Infection ◽  
Neuropsychiatric Symptoms ◽  
Chronic Fatigue ◽  
The Body ◽  
Spike Protein ◽  
Respiratory Mucosa ◽  
Genetic Sequencing

The continuing emergence of variant forms of the SARS-CoV-2 virus is the probable consequence of using the current Covid-19 vaccines. These vaccines do not induce the same immunity as do naturally occurring infections.First, the vaccines are given by intramuscular injections. This is far less effective than natural infection in stimulating the development of virus specific immunoglobulin A (IgA) producing cells and cytotoxic T cells (CTL) within the respiratory mucosa. Virus exposure in a previously vaccinated individual with limited mucosal immunity increases the risk of a persistent, subclinical infection, which will initially be restricted to the superficial mucosa. NIH and CDC officials have alluded to this possibility in advising those who have been vaccinated to continue wearing masks lest they may infect others. The second major distinction between the Covid-19 vaccines and natural infection is the FDA allowance of using only one component as the antigen, namely the spike protein. Deletion or other modifications of a single targeted component can occur more readily as an immune evasion mechanism than concurrent genetic modifications of multiple antigenic components. Covid-19 vaccine evoked immunity will, therefore, exert a strong immunoselective pressure for major modifications or deletion of the spike protein. With successive additional changes in the few remaining viral components that are normally targeted by cellular immunity, as well as the incorporation of sufficient genetic sequences from cells and other microbes; non-immunogenic, pathogenic viruses will then emerge. These viruses will no longer be immunologically restricted to the respiratory mucosa and will become more widespread within the body. The immune evasion/escape mechanism utilized in this manner is termed stealth adaptation. It was initially identified in the cytomegaloviruses of monkeys used to produce polio vaccines. Not only were these viruses probably involved in causing AIDS, but they can account for the rise in many chronic illnesses, such as autism and the chronic fatigue syndrome (CFS). Until proven otherwise, the neuropsychiatric symptoms of the Long Covid syndrome in previously healthy individuals, are consistent with brain infection with stealth adapted coronaviruses. This illness is, therefore, likely to be infectious, including the possibility of transplacental transmission. Testing for stealth adapted viruses in these patients is best performed using virus cultures followed by genetic sequencing. Even though cellular immunity fails to effectively suppress stealth adapted viruses, these viruses as well as the conventional viruses from which they are derived, are still susceptible to a non-immunological anti-virus defense mechanism mediated by the alternative cellular energy (ACE) pathway. This pathway is reflected in an added kinetic activity of the body’s fluids.The environmental life-force energy for the ACE pathway is called KELEA (Kinetic Energy Limiting Electrostatic Attraction). Water with high levels of KELEA is available for clinical studies.Enhancing the ACE pathway in those who are susceptible to severe Covid-19 illness and in Long Covid syndrome patients is arguably preferable to risking the development of new forms of stealth adapted viruses by using the current Covid-19 vaccines.

scholarly journals Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Science ◽  
2021 ◽  
pp. eabh2644 ◽  
Author(s):  
Nuno R. Faria ◽  
Thomas A. Mellan ◽  
Charles Whittaker ◽  
Ingra M. Claro ◽  
Darlan da S. Candido ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Genome Sequencing ◽  
Immune Evasion ◽  
Molecular Clock ◽  
Spike Protein ◽  
Dynamical Model ◽  
Mortality Data ◽  
Clock Analysis ◽  
Protection Against Infection ◽  
Molecular Clock Analysis

Cases of SARS-CoV-2 infection in Manaus, Brazil, resurged in late 2020, despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1, acquired 17 mutations, including a trio in the spike protein (K417T, E484K and N501Y) associated with increased binding to the human ACE2 receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7–2.4-fold more transmissible, and that previous (non-P.1) infection provides 54–79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

scholarly journals Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1192
Author(s):  
Ivana Lazarevic ◽  
Vera Pravica ◽  
Danijela Miljanovic ◽  
Maja Cupic
Keyword(s):  
Immune Evasion ◽  
Human Population ◽  
Evolutionary Rate ◽  
Spike Protein ◽  
Close Monitoring ◽  
Global Level ◽  
Therapeutic Application ◽  
Neutralization Capacity ◽  
Rapid Transmission ◽  
Potential Impact

Despite the slow evolutionary rate of SARS-CoV-2 relative to other RNA viruses, its massive and rapid transmission during the COVID-19 pandemic has enabled it to acquire significant genetic diversity since it first entered the human population. This led to the emergence of numerous variants, some of them recently being labeled “variants of concern” (VOC), due to their potential impact on transmission, morbidity/mortality, and the evasion of neutralization by antibodies elicited by infection, vaccination, or therapeutic application. The potential to evade neutralization is the result of diversity of the target epitopes generated by the accumulation of mutations in the spike protein. While three globally recognized VOCs (Alpha or B.1.1.7, Beta or B.1.351, and Gamma or P.1) remain sensitive to neutralization albeit at reduced levels by the sera of convalescent individuals and recipients of several anti-COVID19 vaccines, the effect of spike variability is much more evident on the neutralization capacity of monoclonal antibodies. The newly recognized VOC Delta or lineage B.1.617.2, as well as locally accepted VOCs (Epsilon or B.1.427/29-US and B1.1.7 with the E484K-UK) are indicating the necessity of close monitoring of new variants on a global level. The VOCs characteristics, their mutational patterns, and the role mutations play in immune evasion are summarized in this review.

scholarly journals Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 821
Author(s):  
Rohitash Yadav ◽  
Jitendra Kumar Chaudhary ◽  
Neeraj Jain ◽  
Pankaj Kumar Chaudhary ◽  
Supriya Khanra ◽  
...  
Keyword(s):  
Host Cell ◽  
Protein S ◽  
Structural Similarity ◽  
Cell Receptor ◽  
Molecular Assembly ◽  
The Body ◽  
Spike Protein ◽  
Structural Proteins ◽  
Structural Protein ◽  
Novel Coronavirus

Coronavirus belongs to the family of Coronaviridae, comprising single-stranded, positive-sense RNA genome (+ ssRNA) of around 26 to 32 kilobases, and has been known to cause infection to a myriad of mammalian hosts, such as humans, cats, bats, civets, dogs, and camels with varied consequences in terms of death and debilitation. Strikingly, novel coronavirus (2019-nCoV), later renamed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and found to be the causative agent of coronavirus disease-19 (COVID-19), shows 88% of sequence identity with bat-SL-CoVZC45 and bat-SL-CoVZXC21, 79% with SARS-CoV and 50% with MERS-CoV, respectively. Despite key amino acid residual variability, there is an incredible structural similarity between the receptor binding domain (RBD) of spike protein (S) of SARS-CoV-2 and SARS-CoV. During infection, spike protein of SARS-CoV-2 compared to SARS-CoV displays 10–20 times greater affinity for its cognate host cell receptor, angiotensin-converting enzyme 2 (ACE2), leading proteolytic cleavage of S protein by transmembrane protease serine 2 (TMPRSS2). Following cellular entry, the ORF-1a and ORF-1ab, located downstream to 5′ end of + ssRNA genome, undergo translation, thereby forming two large polyproteins, pp1a and pp1ab. These polyproteins, following protease-induced cleavage and molecular assembly, form functional viral RNA polymerase, also referred to as replicase. Thereafter, uninterrupted orchestrated replication-transcription molecular events lead to the synthesis of multiple nested sets of subgenomic mRNAs (sgRNAs), which are finally translated to several structural and accessory proteins participating in structure formation and various molecular functions of virus, respectively. These multiple structural proteins assemble and encapsulate genomic RNA (gRNA), resulting in numerous viral progenies, which eventually exit the host cell, and spread infection to rest of the body. In this review, we primarily focus on genomic organization, structural and non-structural protein components, and potential prospective molecular targets for development of therapeutic drugs, convalescent plasm therapy, and a myriad of potential vaccines to tackle SARS-CoV-2 infection.

scholarly journals Argyrophilic grain disease: An underestimated tauopathy

2015 ◽  
Vol 9 (1) ◽  
pp. 2-8 ◽  
Author(s):  
Roberta Diehl Rodriguez ◽  
Lea Tenenholz Grinberg
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Defense Mechanism ◽  
Neuropsychiatric Symptoms ◽  
Argyrophilic Grain Disease ◽  
Coiled Bodies ◽  
Pathologic Features ◽  
High Prevalence ◽  
Argyrophilic Grain ◽  
Argyrophilic Grains

Argyrophilic grain disease (AGD) is an under-recognized, distinct, highly frequent sporadic tauopathy, with a prevalence reaching 31.3% in centenarians. The most common AGD manifestation is slowly progressive amnestic mild cognitive impairment, accompanied by a high prevalence of neuropsychiatric symptoms. AGD diagnosis can only be achieved postmortem based on the finding of its three main pathologic features: argyrophilic grains, oligodendrocytic coiled bodies and neuronal pretangles. AGD is frequently seen together with Alzheimer's disease-type pathology or in association with other neurodegenerative diseases. Recent studies suggest that AGD may be a defense mechanism against the spread of other neuropathological entities, particularly Alzheimer's disease. This review aims to provide an in-depth overview of the current understanding on AGD.

Endodontic Materials: Reactor Response

1988 ◽  
Vol 2 (1) ◽  
pp. 25-28 ◽  
Author(s):  
I.A. Mjör
Keyword(s):  
Side Effects ◽  
Review Paper ◽  
Defense Mechanism ◽  
The Body ◽  
Endodontic Treatment ◽  
Bridge Formation ◽  
Per Se ◽  
Apical Area

This discussion of a review paper on endodontic materials focuses on the need for standardization of this group of materials, including clinical and biological investigations. It was concluded that the search for endodontic materials that are both adhesive to dentin and insoluble must continue. When such materials become available, the defense mechanism of the body would take care of the healing per se. This approach as well as techniques and materials which induce dentin bridge formation in the apical area were considered feasible for improving endodontic treatment. The need to report side-effects of endodontic materials was stressed, and it was suggested that such reports should be mandatory for clinicians and for manufacturers of endodontic materials.

scholarly journals P0517RENAL STEM CELLS (ARPCS) AS A NEPHROPROTECTIVE APPROACH DURING CISPLATIN-INDUCED ACUTE KIDNEY INJURY: A DEFENSE MECHANISM BY EXTRACELLULAR VESICLES CARRYING THE CYP1B1 GENE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
ROSSANA FRANZIN ◽  
Fabio Sallustio ◽  
Claudia Curci ◽  
Simona Simone ◽  
Angela Picerno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Kidney Injury ◽  
Extracellular Vesicles ◽  
Caspase 3 ◽  
Defense Mechanism ◽  
Kidney Injury ◽  
The Body ◽  
Cell Culture Supernatant ◽  
Protective Agent ◽  
Cyp1b1 Gene

Abstract Background and Aims Cisplatin, is a nonspecific cytotoxic agent that primarily interferes with cellular DNA replication and the cell cycle, nevertheless it lacks tumor selectivity and acts also in normal cells. The most serious adverse reaction of cisplatin is Acute Kidney Injury (AKI), limiting its use and efficacy in chemotherapy. Cisplatin nephrotoxicity is observed in more than 30% of older patients, however the mechanism of nephrotoxicity remains unclear and specific preventive measures are not available. Today, there is an urgent need for specific nephroprotective strategies to be used during cisplatin chemotherapy. Recently, we found that tubular stem/progenitor cells (tARPC) are able to protect the tubular epithelial (RPTEC) from cisplatin induced injury, preserving their proliferation and inhibiting apoptosis. The aim of this study was to identify the molecular mechanisms involved in tARPC-mediated resistance to cisplatin. Method Co-cultures of RPTEC cells and tARPCs were exposed to cisplatin (2.5 µM) for 6 h and then kept in culture for 96 h. Gene expression profile was obtained from tARPCs and RPTECs by Agilent SurePrint G3 Human Gene Expression Microarrays. Genespring and R software were used for the analysis. Gene expression data were validated by Real-time PCR. Extracellular vesicles were isolated from cell culture supernatant by miRCURY Exosome Cell/Urine/CSF Kit (Qiagen) and RNA contained in extracellular vesicles was purified, analyzed in quality by Bioanalyzer (RNA nano) and evaluated by qPCR. The BrdU assay and caspase 3 were used to measure proliferation and apoptosis levels. Immunohistochemical expression of activated caspase-3 was used as a marker of apoptosis in RPTECs. Results By a whole-genome gene expression analysis, we found 107 genes specifically modulated by RPTECs in response to cisplatin and, among these, 30 genes induced by ARPCs following the cisplatin damage. In particular, we found a strong upregulation of the CYP1B1 gene (false discovery rate corrected p value <0.05; fold change=4,1). The qPCR confirmed the increase in CYP1B1 levels in the co-cultures with respect to the respective basal conditions (p <0.05). Interestingly, the CYP1B1 mRNA was also enveloped in Extracellular Vesicles released in the cell co-culture media by tARPC and RPTEC after cisplatin exposition. The CYP1B1 gene encodes a member of the cytochrome P450 superfamily of enzymes and the produced enzyme metabolizes procarcinogens, such as polycyclic aromatic hydrocarbons. CYP1B1 has been shown to be active within tumors and is also capable of metabolizing a structurally diverse range of anticancer drugs. It is responsible for the resistance to docetaxel, cisplatin, tamoxifen and nucleoside analogues. CYP1B1 is involved in the detoxification of the body by various exogenous toxic agents, including cisplatin. We found that CYP1B1 gene was expressed at low levels in RPTECs and in cisplatin-damaged RPTECs. Moreover, 96 h days after 2.5 μM exposure to cisplatin, RPTECs reduced the proliferation and underwent in apoptosis, as showed by caspase 3. However, in co-culture with ARPCs, ARPC cellular and extracellular vesicles CYP1B1 gene expression significantly increased, the apoptotic process was stopped and RPTECs increased their proliferation rate. These data support the hypothesis that ARPCs are sensor of cisplatin damaged-RPTEC and confers cisplatin resistance by transferring CYP1B1 gene in extracellular vesicles. Conclusion This is the first evidence of a cisplatin-induced overexpression of CYP1b1 in renal epithelial cells as a defense mechanism against cisplatin toxicity. This is consistent with our previous data showing that renal progenitors are resistant to cisplatin. The findings may have biological and clinical significance in terms of their implications in cellular communications and potential use of CYP1B1 as biomarkers for AKI induced by cisplatin or as protective agent.

scholarly journals ANALYSIS OF IMMUNE ESCAPE VARIANTS FROM ANTIBODY-BASED THERAPEUTICS AGAINST COVID-19.

2021 ◽  
Author(s):  
Daniele Focosi ◽  
Fabrizio Maggi ◽  
Massimo Franchini ◽  
Scott McConnell ◽  
Arturo Casadevall
Keyword(s):  
Public Health ◽  
Monoclonal Antibodies ◽  
Immune Evasion ◽  
Immune Escape ◽  
Selective Pressure ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
Single Amino Acid ◽  
Receptor Binding Domain ◽  
Amino Acid Mutations

Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former is mainly associated with specific single amino acid mutations at residues within the receptor-binding domain (e.g., E484K/Q, Q493R, and S494P), the few cases of immune evasion after CCP were associated with recurrent deletions within the N-terminal domain of Spike protein (e.g, delHV69-70, delLGVY141-144 and delAL243-244). Continuous genomic monitoring of non-responders is needed to better understand immune escape frequencies and fitness of emerging variants.

scholarly journals COMPARATIVE IMMUNOGENICITY OF BNT162b2 mRNA VACCINE WITH NATURAL COVID-19 INFECTION

2021 ◽  
Author(s):  
Mina Psichogiou ◽  
Andreas Karabinis ◽  
Garyphallia Poulakou ◽  
Anastasia Antoniadou ◽  
Anastasia Kotanidou ◽  
...  
Keyword(s):  
Health Care Workers ◽  
Nucleocapsid Protein ◽  
Natural Infection ◽  
Multivariable Analysis ◽  
Severe Infection ◽  
Spike Protein ◽  
Care Workers ◽  
Number Of Individuals ◽  
High Immunogenicity ◽  
Clinical Subgroup

The mRNA vaccine BNT162b2 has proven highly effective and currently many millions are being vaccinated. There are limited and conflicting data from immunogenicity studies on the effects of age, gender, vaccination side effects (VSE), risk factors for severe COVID-19 (RFS-COV), obesity (BMI) and previous SARS-CoV-2 (Pr-CoV) Moreover, immunogenicity data from COVID-19 patients comparing various disease categories of natural infection i.e. asymptomatic vs mild vs moderate vs severe infection are sparse, and include limited number of individuals. This study included 871 vaccinated health care workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by a quantative assay measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD) and anti-SARS-CoV-2 against nucleocapsid protein (anti-N). Samples were collected 1-2 weeks after completion of the 2nd dose in the vaccinated HCWs and 15-59 days post symptoms onset in patients with natural infection. The concentration of anti-RBD in vaccinated individuals after multivariable analysis was significantly associated with age, gender, VSE and Pr-CoV. Specifically, anti-RBD median levels (95% CI) were lower by 2,466 (651-5,583), 6,228 (3,254-9,203) and 7,651 (4,479-10,823) AU/ml in 35-44, 45-54, 55-70 yrs respectively, compared with 18-34 yrs group. In females, median levels of anti-RBD were higher by 2,823 (859-4,787) compared with males, in individuals with VSE were higher by 5,024 (3,122-6,926) compared with no VSE, and in HCWs with Pr-CoV were higher by 9,971 (5,158-14,783) AU/ml compared with HCWs without Pr-CoV. Among individuals with natural infection, the median anti-RBD levels were 14.8 times higher in patients with critical COVID-19 infection compared with non-hospitalized individuals. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 up to 19.4 according to the clinical subgroup of natural infection. This study proves the high immunogenicity of BNT162b2 vaccine although its sustainability remains to be seen. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection may facilitate early decisions for vaccine evaluation in clinical trials.

scholarly journals Contraception Reduces Breast Milk Protein Level of Breastfeeding Mothers in Jember, East Java, Indonesia

2020 ◽  
Vol 4 (5) ◽  
pp. 153-157
Author(s):  
Nuzula Irfa Nuriana ◽  
FX. Ady Soesetijo ◽  
Candra Bumi
Keyword(s):  
Breast Milk ◽  
Protein Level ◽  
Respiratory Tract Infections ◽  
Milk Protein ◽  
Defense Mechanism ◽  
The Body ◽  
P Value ◽  
Cross Sectional ◽  
Tract Infections ◽  
Keywords Infection

The protein level of breast milk affected the growth and development of infants. Protein has special function which is irreplaceable by other nutrients to form and protect the body cells. Protein also plays a role as antibody, functions as the body defense mechanism against various diseases and infections. Infant death in Indonesia is mostly caused by respiratory tract infections and diarrhea. Breastfeeding can help to prevent the occurrence of morbidity and mortality of infants and toddlers in which the breast milk contains many essential nutrients needed by the body, one of them is protein. The aim of this research was to analyze the effect of contraception on breast milk protein level of breastfeeding mothers in Jember regency. The design of this research was observational analytic with cross sectional approach, using statistic test of logistic regression. The result of the research showed that the effect of contraception on the protein level of breast milk obtained p-value=0.021 with Exp(B)=566.263. Based on the research, it can be concluded that there was an effect of contraception on breast milk protein level. Keywords: infection; breastmilk protein; contraception

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