Medical, Genomic, and Evolutionary Aspects of the Peptide Sharing between Pathogens, Primates, and Humans

Abstract

Comparing mammalian proteomes for molecular mimicry with infectious pathogens highlights the highest levels of heptapeptide sharing between pathogens and human, murine, and rat proteomes, while the peptide sharing level is minimal (or absent) with proteomes from nonhuman primates such as gorilla, chimpanzee, and rhesus macaque. From the medical point of view, the data might be useful to clinicians and vaccinologists to develop and evaluate immunomodulatory and immunotherapeutic approaches. As a matter of fact, primates seem to be unreliable animal models for revealing potential autoimmune events in preclinical testing of immunotherapies. In terms of genomics, the scarce or absent peptide sharing between pathogens and primates versus the massive peptide sharing existing between pathogens and humans lets foresee mechanisms of pathogen sequence insertion/deletion/alteration that have differently operated in mammals over evolutionary timescales. Why and how the human genome has been colonized by pathogen sequences and why and how primates escaped such a colonization appears to be the new scientific challenge in our efforts to understand not only the origin of Homo sapiens but also his autoimmune diseasome.

Vaccine- and natural infection-induced mechanisms that could modulate vaccine safety

“…This risk of cross-reactivity further increases when considering that it cannot be estimated with the current vaccine pre-clinical tests [ 153 , 154 ]. Indeed, the level of peptide sharing is highest between pathogens and human, murine, and rat proteomes, and is lowest (or absent) with proteomes from nonhuman primates such as gorilla, chimpanzee, and rhesus macaque.…”

Coronavirus-associated molecular mimicry through homology to a SARS-CoV-2 peptide could be leading to susceptibility in patients with HLA-A*02:01 and HLA-A*24:02 serotypes

“…Vaccine targets are already studied for COVID-19 [65], but cross-reactivity risk in the adjuvant-vaccine for the individuals with genetic susceptibility should also be considered [61], together with the discussed considerations in terms of the autoimmunity risk, in general. Similar studies as those mentioned here [7][8][9][10][11][12]49,50] need to be performed, maybe even by taking possible variations in the genetic makeup into account. In the end, we would like to remind once more the useful suggestion of implementing HLA typing into COVID-19 tests and clinical trials [35], and the considerations about tests on the animals [11].…”

“…Similar studies as those mentioned here [7–12,49,50] need to be performed, maybe even by taking possible variations in the genetic makeup into account. In the end, we would like to remind once more the useful suggestion of implementing HLA typing into COVID-19 tests and clinical trials [35], and the considerations about tests on the animals [11].…”

Lack of Molecular Mimicry between Nonhuman Primates and Infectious Pathogens: The Possible Genetic Bases

“…[71][72][73] In sum, it is not surprising that primates are not good models for many major human diseases/conditions [42][43][44] and for preclinical vaccine tests. 29,30 Literature data and the present data might explain the inefficacy and the problematics of vaccines, [51][52][53][54][55][56][57][58][59][60] thus inviting researchers and vaccinologists to study, identify, and use the correct animal models capable of revealing potential autoimmune pathogenicity connected to the peptide sharing.…”