Viral immunogenic footprints conferring T cell cross-protection to SARS-CoV-2 and its variants

Abstract

COVID-19 brought scenes from sci-fi movies into real life. Infected individuals include asymptomatic cases to severe disease leading to death, suggesting the involvement of the genetic constitution of populations and pathogens contributing to differential individuals’ outcomes. To investigate shared immunogenic features between SARS-CoV-2 targets and other coronaviruses, we modeled their peptides in 3D structures of HLA-A*02:01 (pMHC), comparing their molecular surfaces These structures were also compared with a panel of epitopes from unrelated viruses, looking for potential triggers conferring cross-protection in uninfected individuals. As expected, SARS-CoV 1 and 2 peptides share molecular and physicochemical features, providing an explanation for the verified experimental immunogenicity among them. Surprisingly, even discordant sequences from human coronaviruses 229E, OC43 and epitopes from unrelated viruses involved in endemic human infections exhibit similar fingerprints of immunogenicity with SARS-CoV-2 peptides. The same approach indicates a conserved CD8+ T cell recognition between Wuhan SARS-CoV-2 sequences and altered peptides from Variants of Concern. Examination of structural data over epitope sequence analysis here could explain how previous infections may produce a heterologous immunity response in a global scale against emergent diseases such as Covid-19, mitigating its full lethal potential, and paves the way for the development of wide spectrum vaccine development.

SARS‐CoV‐2, periodontal pathogens, and host factors: The trinity of oral post‐acute sequelae of COVID‐19

“…81 The ACE2 ECD reportedly upregulates inflammation. 81,82 Moreover, because ADAM17 causes the shedding of cytokine receptors from immune effector cells, its activity results in the accumulation of soluble cytokines, such as IL-1 and IL-6 (Table 1), and their accumulation results in clinical manifestations. [83][84][85][86][87][88][89] As the main endogenous pyrogen, IL-1 causes fever, while IL-6 stimulates B lymphocyte proliferation and antibody production, possibly increasing autoantibody synthesis.…”

“…As a shedding protease, ADAM17 cleaves and subsequently releases the extracellular domain (ECD) of the host receptor ACE2 upon the initial binding between SARS‐CoV‐2 spike protein and ACE2 81 . The ACE2 ECD reportedly upregulates inflammation 81,82 . Moreover, because ADAM17 causes the shedding of cytokine receptors from immune effector cells, its activity results in the accumulation of soluble cytokines, such as IL‐1 and IL‐6 (Table 1), and their accumulation results in clinical manifestations 83–89 .…”