Potential Cross-Reactive Immunity to SARS-CoV-2 From Common Human Pathogens and Vaccines.

Pedro A Reche

doi:10.3389/fimmu.2020.586984

Abstract

The recently emerged SARS-CoV-2 causing the ongoing COVID-19 pandemic is particularly virulent in the elderly while children are largely spared. Here, we explored the potential role of cross-reactive immunity acquired from pediatric vaccinations and exposure to common human pathogens in the protection and pathology of COVID-19. To that end, we sought for peptide matches to SARS-CoV-2 (identity ≥ 80%, in at least eight residues) in the proteomes of 25 human pathogens and in vaccine antigens, and subsequently predicted their T and B cell reactivity to identify potential cross-reactive epitopes. We found that viruses subject to pediatric vaccinations do not contain cross-reactive epitopes with SARS-CoV-2, precluding that they can provide any general protection against COVID-19. Likewise, common viruses including rhinovirus, respiratory syncytial virus, influenza virus, and several herpesviruses are also poor or null sources of cross-reactive immunity to SARS-CoV-2, discarding that immunological memory against these viruses can have any general protective or pathological role in COVID-19. In contrast, we found combination vaccines for treating diphtheria, tetanus, and pertussis infectious diseases (DTP vaccine) to be significant sources of potential cross-reactive immunity to SARS-CoV-2. DTP cross-reactive epitopes with SARS-CoV-2 include numerous CD8 and CD4 T cell epitopes with broad population protection coverage and potentially neutralizing B cell epitopes in SARS-CoV-2 Spike protein. Worldwide, children receive several DTP vaccinations, including three-four doses the first year of life and one at 4–6 years of age. Moreover, a low antigenic Tdap dose is also given at ages 9–14. Thereby, children may well be protected from SARS-CoV-2 through cross-reactive immunity elicited by DTP vaccinations, supporting testing in the general population to prevent COVID-19.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emergent virus identified in late 2019 as the etiological agent behind a mysterious outbreak of pneumonia in Wuhan, China [1, 2]
T cells can be divided into CD4 and CD8 T cells which recognize peptides displayed in the cell surface of antigen presenting cells bound to class I and class II major histocompatibility complex (MHC) molecules, respectively
We anticipated CD4 and CD8 T cell epitopes by predicting peptide binding to class I and class II human MHC molecules

Summary

INTRODUCTION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new emergent virus identified in late 2019 as the etiological agent behind a mysterious outbreak of pneumonia in Wuhan, China [1, 2]. Thereby, to test our hypothesis and identify potential sources of cross-reactive immunity to SARS-CoV-2, we conducted a systematic search for peptide matches to SARS-CoV-2 in 25 human pathogens including 18 viruses and 7 bacteria—the majority targeted by vaccinations—and in selected vaccine antigens, and predicted their T and B cell reactivity to identify cross-reactive epitopes. Among the viruses without available vaccine, we considered herpes simplex virus 1 and 2, Epstein–Barr virus, human cytomegalovirus, human rhinovirus A, B, and C and respiratory syncytial virus A and B, which are all prevalent in the population After these analyses, we found numerous cross-reactive epitopes between antigens in tetatus, diphteria, and pertussis (DTP) vaccines and SARS-CoV-2, including T cell epitopes with broad population protection coverage and potentially neutralizing B-cell epitopes. Our results clearly support that cross-reactive immunity from DTP vaccines can be protecting children against SARSCoV-2 and could protect the general population

METHODS

Other Procedures

RESULTS AND DISCUSSION

D T aP wP MenB

DATA AVAILABILITY STATEMENT