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Cross-Protection Induced by Highly Conserved Human B, CD4

Swayam Prakash1, Nisha R Dhanushkodi1, Latifa Zayou1

  • 1Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697.

Biorxiv : the Preprint Server for Biology
|June 9, 2023
PubMed

Insights

A novel multi-epitope pan-Coronavirus vaccine offers broad protection against SARS-CoV-2 variants of concern (VOCs). This vaccine is safe and elicits robust immune responses, reducing COVID-19 severity and mortality.

Area of Science:

  • Immunology
  • Vaccinology
  • Virology

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, continues to pose a significant global health threat due to the emergence of numerous variants of concern (VOCs).
  • Existing vaccines face challenges in providing broad protection against the continuously evolving SARS-CoV-2 strains, necessitating the development of next-generation vaccines.
  • The high mortality rate associated with COVID-19 underscores the urgent need for effective pan-Coronavirus vaccines.

Approach:

  • A multi-epitope vaccine was designed incorporating conserved B cell, CD4+, and CD8+ T cell epitopes from SARS-CoV-2.
  • The vaccine's safety, immunogenicity, and cross-protective immunity were evaluated in a triple transgenic h-ACE-2-HLA-A2/DR mouse model against six SARS-CoV-2 VOCs.
  • Epitopes were selected for their conservation across VOCs and recognition by T cells from asymptomatic COVID-19 patients.

Key Points:

  • The pan-Coronavirus vaccine demonstrated an excellent safety profile in the preclinical model.
  • It successfully induced high frequencies of lung-resident functional CD8+ and CD4+ T cells (TEM and TRM).
  • The vaccine provided significant protection against virus replication, lung pathology, and mortality caused by Alpha, Beta, Gamma, Delta, and Omicron VOCs.

Conclusions:

  • A multi-epitope vaccine strategy targeting conserved SARS-CoV-2 epitopes is effective in inducing cross-protective immunity.
  • This pan-Coronavirus vaccine cleared viral replication and reduced COVID-19-related lung pathology and death.
  • The findings support the development of this vaccine as a next-generation solution against SARS-CoV-2 VOCs.
Abstract

Keywords:
AntibodiesCD4+ T cellsCD8+ T cellsCOVID-19EpitopesImmunityImmunopathologySARS-CoV-2SL-CoVsVaccineVariants of Concern

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