Inter-Pathogen Peptide Sharing and the Original Antigenic Sin: Solving a Paradox

Abstract

Aims:To analyse the peptide commonality among viral, bacterial, and protozoan pathogens, and the immunopathologic consequences in the human host.Methods:HPV16, HCMV,C. diphtheriae, B. pertussis, C. tetani, T. gondii,andT. cruziwere analysed for common amino acid sequences that are additionally shared with the human host. The pentapeptide, a minimal immune determinant in humoral and cellular immune recognition, was used as a measurement unit of the peptide similarity level. Molecular modeling was applied to compare the amino acid contexts containing common minimal determinants.Results:Twenty-nine pentapeptides were found to occur, even hundreds of times, throughout the analyzed pathogen proteomes as well as in the human proteome. Such vast peptide commonalities together with molecular modeling data support the possibility that a pre-existing immune response to a first pathogen can be boosted by a successive exposure to a second different pathogen,i.e., the primary response to a pathogen can be transformed into a secondary response to a previously encountered different pathogen. Two possible consequences emerge. Firstly, no responses might be elicited against the pathogen lastly encountered either by infection or active immunization, but reactions could occur only with the early sensitizing pathogen, which is no more present in the organism. Secondly, the immune response boosted by the pathogen lastly encountered will find a way out by cross-reacting with human proteins.Conclusion:This study might explain the “original antigenic sin” phenomenon described seven decades ago [Francis T. Jr. Ann Intern Med 1953;39:203], thus providing explanations for vaccine failures and offering possible clues for designing successful vaccines.

From influenza infection to anti-ADAMTS13 autoantibodies via cross-reactivity

“…Moreover, the peptide sharing is immunologically significant by being most of the shared peptides also part of experimentally validated epitopes (Table 2). Hence, the present study substantiates the hypothesis of cross-reactivity involvement in the generation of anti-ADAMTS13 AAbs following influenza infection, in this way flanking previous findings [53][54][55][56][57] that indicate autoimmune cross-reactions as a basic mechanism in the generation of autoimmune diseases following infections. The data warrant further collaborative research efforts, especially in light of the fact that low levels of ADAMTS13 protease are a risk factor for the development of myocardial infarction [58,59], stroke [59][60][61], preeclampsia [61], disseminated intravascular coagulation [62], cerebrovascular disease [63], etc.…”

Influenza and sudden unexpected death: the possible role of peptide cross-reactivity

“…Given these caveats, the conclusion of this study is that the data discussed might help our understanding of what has been and is still considered as a mysterious enigmatic phenomenon, ie, the influenza-associated pathogenicity [74,75,76].…”

Corona (COVID-19) time musings: Our involvement in COVID-19 pathogenesis, diagnosis, treatment and vaccine planning

“…We believe that this vaccine will be approved through an expedited process thus not necessarily enabling surveillance due to the shortness of time thus eventual side effects of the vaccine could not be evaluated. The amino acid sequences of the virus like in other viruses, might have a cross-reaction with the human body sequences [28][29][30][31]. Therefore, one of the side effects of giving a MASS vaccine could be an mergence of autoimmune diseases especially in individuals who are genetically prone for autoimmunity [28][29][30][31].…”

“…The amino acid sequences of the virus like in other viruses, might have a cross-reaction with the human body sequences [28][29][30][31]. Therefore, one of the side effects of giving a MASS vaccine could be an mergence of autoimmune diseases especially in individuals who are genetically prone for autoimmunity [28][29][30][31]. Actually the corronavirus was reported to induce retinal autoimmune disease in an experimental model [32].…”