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This communication concerns a crucial query in immunology, that is, the dimension of an epitope. The issue has essential implications in vaccine formulations., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

This study calls attention on molecular mimicry and the consequent autoimmune cross reactivity as the molecular mechanism that can cause adverse events following meningococcal B vaccination and warns against active immunizations based on entire antigen., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

This study analyzed KISS1 and its receptor KISSR for peptide sharing with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was found that SARS-CoV-2 shares numerous minimal immune pentapeptide determinants with KISSR only. The peptide sharing has a high immunologic potential since almost all the common peptides are present in 101 SARS-CoV-2-derived immunoreactive epitopes. Data are in favor of configuring molecular mimicry as an epigenetic factor that can alter KISSR thus causing the hypogonadotropic hypogonadism syndrome with which altered KISSR associates., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Background and Aim  Immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in newborns and children after prophylactic immunization is currently a relevant research topic. The present study analyzes the issue by examining the possibility that the anti-SARS-CoV-2 immune responses are not uniquely directed against the virus but can-via molecular mimicry and the consequent cross-reactivity-also hit human proteins involved in infantile diseases. Methods  Human proteins that-if altered-associate with infantile disorders were searched for minimal immune pentapeptide determinants shared with SARS-CoV-2 spike glycoprotein (gp). Then, the shared pentapeptides were analyzed for immunologic potential and immunologic imprinting phenomena. Results  Comparative sequence analysis shows that: (1) numerous pentapeptides (namely, 54) are common to SARS-CoV-2 spike gp and human proteins that, when altered, are linked to infantile diseases; (2) all the shared peptides have an immunologic potential since they are present in experimentally validated SARS-CoV-2 spike gp-derived epitopes; and (3) many of the shared peptides are also hosted in infectious pathogens to which children can have already been exposed, thus making immunologic imprint phenomena feasible. Conclusion  Molecular mimicry and the consequent cross-reactivity can represent the mechanism that connects exposure to SARS-CoV-2 and various pediatric diseases, with a fundamental role of the immunologic memory and the history of the child's infections in determining and specifying the immune response and the pathologic autoimmune sequela., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

This study examined respiratory syncytial virus (RSV) F glycoprotein (gp) antigen for molecular mimicry with the human proteome. It was found that the viral antigen presents an impressive number of pentapeptides (namely, 525 out of 570) in common with the human proteome, with viral sequences widely and repeatedly distributed among 3,762 human proteins implicated in crucial fundamental cellular functions. The data can have implications for anti-RSV vaccines. Indeed, the high level of molecular mimicry can lead to cross-reactivity and autoimmunity, and invites to follow safer vaccinal protocols based on pentapeptide sequences uniquely present in the viral antigen., Competing Interests: Conflicts of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

The devastating complications of coronavirus disease 2019 (COVID-19) result from an individual's dysfunctional immune response following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events ultimately leading to COVID-19. The current study identifies eighty immune system dysfunction-enabling toxic stressors and behaviors (hereafter called modifiable contributing factors (CFs)) that also link directly to COVID-19. Each CF is assigned to one of the five categories in the CF taxonomy shown in Section 3.3.: Lifestyle (e.g., diet, substance abuse); Iatrogenic (e.g., drugs, surgery); Biotoxins (e.g., micro-organisms, mycotoxins); Occupational/Environmental (e.g., heavy metals, pesticides); Psychosocial/Socioeconomic (e.g., chronic stress, lower education). The current study shows how each modifiable factor contributes to decreased immune system capability, increased inflammation and coagulation, and increased neural damage and neurodegeneration. It is unclear how real progress can be made in combatting COVID-19 and other similar diseases caused by viral variants without addressing and eliminating these modifiable CFs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Epstein-Barr nuclear antigen 1 (EBNA1) protein synthesis is inhibited during Epstein-Barr virus (EBV) latency and is resumed in EBV (re)activation. In analyzing the molecular mechanisms underpinning the translation of EBNA1 in the human host, this article deals with two orders of data. First, it shows that the heavily biased codon usage of the EBNA1 open reading frame cannot be translated due to its noncompliance with the human codon usage pattern and the corresponding tRNA pool. The EBNA1 codon bias resides in the sequence composed exclusively of glycine and alanine, i.e., the Gly-Ala repeat (GAR). Removal of the nucleotide sequence coding for GAR results in an EBNA1 codon usage pattern with a lower codon bias, thus conferring translatability to EBNA1. Second, the data bring cell proliferation to the fore as a conditio sine qua non for qualitatively and quantitatively modifying the host's tRNA pool as required by the translational needs of EBNA1, thus enabling viral reactivation. Taken together, the present work provides a biochemical mechanism for the pathogen's shift from latency to (re)activation and confirms the role of human codon usage as a first-line tool of innate immunity in inhibiting pathogens' expression. Immunologically, this study cautions against using codon optimization and proliferation-inducing substances such as glucocorticoids and adjuvants, which can (re)activate the otherwise quiescent, asymptomatic, and innocuous EBV infection. Lastly, the data pose the question whether the causal pathogenic role attributed to EBV should instead be ascribed to the carcinogenesis-associated cellular proliferation., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Objective  At present, false negatives/positives have been reported in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) diagnostics. Searching for the molecular basis of such tests' unreliability, this study aimed at defining how specific are the sequences used in serological and polymerase chain reaction (PCR) tests to detect SARS-CoV-2. Materials and Methods  Analyses were performed on the leading SARS-CoV-2 biomarker spike glycoprotein (gp). Sharing of peptide sequences between the spike antigen and the human host was analyzed using the Peptide Search program from Uniprot database. Sharing of oligonucleotide sequences was investigated using the nucleotide Basic Local Alignment Search Tool (BLASTn) from National Center for Biotechnology Information (NCBI). Results  Two main points stand out: (1) a massive pentapeptide sharing exists between the spike gp and the human proteome, and only a limited number of pentapeptides (namely 107) identify SARS-CoV-2 spike gp as nonself when compared with the human proteome, and (2) the small phenetic difference practically disappears at the genetic level. Indeed, almost all of the 107 pentadecameric nucleotide sequences coding for the pentapeptides unique to SARS-CoV-2 spike gp are present in human nucleic acids too. Conclusion  The data are of immunological significance for defining the issue of the viral versus human specificity and likely explain the fact that false positives can occur in serological and PCR tests for SARS-CoV-2 detection., Competing Interests: Conflicts of Interest None declared., (The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background  Contrary to immunological expectations, decay of adaptive responses against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) characterizes recovered patients compared with patients who had a severe disease course or died following SARS-CoV-2 infection. This raises the question of the causes of the virus-induced immune immunosuppression. Searching for molecular link(s) between SARS-CoV-2 immunization and the decay of the adaptive immune responses, SARS-CoV-2 proteome was analyzed for molecular mimicry with human proteins related to immunodeficiency. The aim was to verify the possibility of cross-reactions capable of destroying the adaptive immune response triggered by SARS-CoV-2. Materials and Methods  Human immunodeficiency-related proteins were collected from UniProt database and analyzed for sharing of minimal immune determinants with the SARS-CoV-2 proteome. Results  Molecular mimicry and consequent potential cross-reactivity exist between SARS-CoV-2 proteome and human immunoregulatory proteins such as nuclear factor kappa B (NFKB), and variable diversity joining V(D)J recombination-activating gene (RAG). Conclusion  The data (1) support molecular mimicry and the associated potential cross-reactivity as a mechanism that can underlie self-reactivity against proteins involved in B- and T-cells activation/development, and (2) suggest that the extent of the immunosuppression is dictated by the extent of the immune responses themselves. The higher the titer of the immune responses triggered by SARS-CoV-2 immunization, the more severe can be the cross-reactions against the human immunodeficiency-related proteins, the more severe the immunosuppression. Hence, SARS-CoV-2-induced immunosuppression can be defined as a molecular mimicry syndrome. Clinically, the data imply that booster doses of SARS-CoV-2 vaccines may have opposite results to those expected., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

This study shows that oligonucleotide sequences are shared between the human genome and primers that have been proposed/used for SARS-CoV-2 detection by polymerase chain reaction (PCR). The high level of sharing (namely, up to 19mer with a maximum number of gaps equal to 2) might bear implications for the diagnostic validity of SARS-CoV-2 detection by PCR., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

The devastating complications of coronavirus disease 2019 (COVID‑19) result from the dysfunctional immune response of an individual following the initial severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS‑CoV‑2 exploits the dysfunctional immune system to trigger a chain of events, ultimately leading to COVID‑19. The authors have previously identified a number of contributing factors (CFs) common to myriad chronic diseases. Based on these observations, it was hypothesized that there may be a significant overlap between CFs associated with COVID‑19 and gastrointestinal cancer (GIC). Thus, in the present study, a streamlined dot‑product approach was used initially to identify potential CFs that affect COVID‑19 and GIC directly (i.e., the simultaneous occurrence of CFs and disease in the same article). The nascent character of the COVID‑19 core literature (~1‑year‑old) did not allow sufficient time for the direct effects of numerous CFs on COVID‑19 to emerge from laboratory experiments and epidemiological studies. Therefore, a literature‑related discovery approach was used to augment the COVID‑19 core literature‑based 'direct impact' CFs with discovery‑based 'indirect impact' CFs [CFs were identified in the non‑COVID‑19 biomedical literature that had the same biomarker impact pattern (e.g., hyperinflammation, hypercoagulation, hypoxia, etc.) as was shown in the COVID‑19 literature]. Approximately 2,250 candidate direct impact CFs in common between GIC and COVID‑19 were identified, albeit some being variants of the same concept. As commonality proof of concept, 75 potential CFs that appeared promising were selected, and 63 overlapping COVID‑19/GIC potential/candidate CFs were validated with biological plausibility. In total, 42 of the 63 were overlapping direct impact COVID‑19/GIC CFs, and the remaining 21 were candidate GIC CFs that overlapped with indirect impact COVID‑19 CFs. On the whole, the present study demonstrates that COVID‑19 and GIC share a number of common risk/CFs, including behaviors and toxic exposures, that impair immune function. A key component of immune system health is the removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention.

Introduction: Oogenesis, the process of egg production by the ovary, involves a complex differentiation program leading to the production of functional oocytes. This process comprises a sequential pathway of steps that are finely regulated. The question related to SARS-CoV-2 infection and fertility has been evoked for several reasons, including the mechanism of molecular mimicry, which may contribute to female infertility by leading to the generation of deleterious autoantibodies, possibly contributing to the onset of an autoimmune disease in infected patients., Objective: The immunological potential of the peptides shared between SARS-CoV-2 spike glycoprotein and oogenesis-related proteins; Thus we planned a systematic study to improve our understanding of the possible effects of SARS-CoV-2 infection on female fertility using the angle of molecular mimicry as a starting point., Methods: A library of 82 human proteins linked to oogenesis was assembled at random from UniProtKB database using oogenesis, uterine receptivity, decidualization, and placentation as a key words. For the analyses, an artificial polyprotein was built by joining the 82 a sequences of the oogenesis-associated proteins. These were analyzed by searching the Immune Epitope DataBase for immunoreactive SARS-CoV-2 spike glycoprotein epitopes hosting the shared pentapeptides., Results: SARS-CoV-2 spike glycoprotein was found to share 41 minimal immune determinants, that is, pentapeptides, with 27 human proteins that relate to oogenesis, uterine receptivity, decidualization, and placentation. All the shared pentapeptides that we identified, with the exception of four, are also present in SARS-CoV-2 spike glycoprotein-derived epitopes that have been experimentally validated as immunoreactive., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This literature review described the genetic and biochemical factors that may have been overlooked in the formulation of vaccines and that most likely underlie possible issues with mass vaccination., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Despite the existence of potent anti-inflammatory biological drugs e.g., anti-TNF and anti IL-6 receptor antibodies, for treating chronic inflammatory and autoimmune diseases, these are costly and not specific. Cheaper oral available drugs remain an unmet need. Expression of the acute phase protein Serum Amyloid A (SAA) is dependent on release of pro-inflammatory cytokines IL-1, IL-6 and TNF-α during inflammation. Conversely, SAA induces pro-inflammatory cytokine secretion, including Th17, leading to a pathogenic vicious cycle and chronic inflammation. 5- MER peptide (5-MP) MTADV (methionine-threonine-alanine-aspartic acid-valine), also called Amilo-5MER, was originally derived from a sequence of a pro-inflammatory CD44 variant isolated from synovial fluid of a Rheumatoid Arthritis (RA) patient. This human peptide displays an efficient anti-inflammatory effects to ameliorate pathology and clinical symptoms in mouse models of RA, Inflammatory Bowel Disease (IBD) and Multiple Sclerosis (MS). Bioinformatics and qRT-PCR revealed that 5-MP, administrated to encephalomyelytic mice, up-regulates genes contributing to chronic inflammation resistance. Mass spectrometry of proteins that were pulled down from an RA synovial cell extract with biotinylated 5-MP, showed that it binds SAA. 5-MP disrupted SAA assembly, which is correlated with its pro-inflammatory activity. The peptide MTADV (but not scrambled TMVAD) significantly inhibited the release of pro-inflammatory cytokines IL-6 and IL-1β from SAA-activated human fibroblasts, THP-1 monocytes and peripheral blood mononuclear cells. 5-MP suppresses the pro-inflammatory IL-6 release from SAA-activated cells, but not from non-activated cells. 5-MP could not display therapeutic activity in rats, which are SAA deficient, but does inhibit inflammations in animal models of IBD and MS, both are SAA-dependent, as shown by others in SAA knockout mice. In conclusion, 5-MP suppresses chronic inflammation in animal models of RA, IBD and MS, which are SAA-dependent, but not in animal models, which are SAA-independent., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)