Cross-reactive antibodies elicited to conserved epitopes on SARS-CoV-2 spike protein after infection and vaccination

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic, leading to millions of deaths globally.
• Increasing prevalence of novel coronavirus infections necessitates strategies for broad protection.
• Understanding cross-reactive immune responses is crucial for designing effective vaccines and therapeutics against diverse coronavirus strains.

Purpose of the Study:

• To investigate antibody cross-reactivity to SARS-CoV-2 and related betacoronaviruses in infected or vaccinated individuals.
• To evaluate a peptide-conjugate vaccine targeting a conserved SARS-CoV-2 spike epitope for cross-reactive immune responses.
• To identify conserved epitopes that elicit broad protection against coronaviruses and potentially other pathogens.

Main Methods:

• Analysis of antibody responses in individuals with prior SARS-CoV-2 infection or BNT162b2 vaccination.
• Design and immunization of mice with a peptide-conjugate vaccine encoding a conserved SARS-CoV-2 S2 spike epitope.
• Assessment of cross-reactive antibody binding to various coronaviruses.
• Bioinformatic analysis to identify sequence homology between viral epitopes and host proteins.

Main Results:

• Antibody responses from SARS-CoV-2 infection or BNT162b2 vaccination demonstrated cross-reactivity with related betacoronaviruses.
• The peptide-conjugate vaccine induced antibodies that bound to both SARS-CoV-2 and other coronaviruses.
• The targeted conserved spike epitope exhibited sequence homology with proteins found in the gut microbiota.
• This epitope could prime immune responses in humans.

Conclusions:

• Conserved SARS-CoV-2 epitopes can elicit cross-reactive immune responses against related coronaviruses.
• These conserved epitopes also interact with host bacteria, suggesting a role in broader immune priming.
• Identified conserved epitopes represent promising targets for the development of universal coronavirus vaccines and therapeutics.