A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) presents unique evolutionary adaptations contributing to its infectivity.
• Effective vaccine development requires targeting conserved viral regions and novel adaptations presented by MHC class I and II.
• Identifying epitopes dissimilar from the human proteome is crucial for vaccine safety and efficacy.

Purpose of the Study:

• To propose a vaccination strategy for SARS-CoV-2.
• To identify conserved and adaptive viral epitopes for vaccine design.
• To develop a vaccine candidate targeting unique SARS-CoV-2 vulnerabilities for a robust immune response.

Main Methods:

• Identification of highly conserved viral regions and newly acquired adaptations.
• Analysis of epitopes presented by MHC class I and II across the human population.
• Prediction of B cell epitopes dissimilar from the human proteome.
• Selection of 65 peptide sequences for vaccine constructs (DNA, mRNA, synthetic peptide).

Main Results:

• A set of 65 peptide sequences identified as potential vaccine candidates.
• Inclusion of epitopes from evolutionarily divergent spike protein regions enhancing ACE2 receptor binding.
• Inclusion of epitopes from a novel furin cleavage site promoting membrane fusion.
• Proposed strategy targets unique SARS-CoV-2 vulnerabilities.

Conclusions:

• The proposed vaccination strategy is expected to be safe and effective.
• The vaccine candidate can be rapidly tested using various construct types.
• This approach aims to engage a robust adaptive immune response in the majority of the human population.
• The strategy focuses on specific vulnerabilities of SARS-CoV-2 for enhanced efficacy.