The SARS-CoV-2 virus has caused a global crisis, resulting in 0.5 billion
infections and over 6 million deaths as of March 2022. Fortunately,
infection and hospitalization rates were curbed due to the rollout of
DNA and
mRNA vaccines. However, the efficacy of these
vaccines significantly drops a few months post immunization, from 88% down to 47% in the case of the Pfizer
BNT162 vaccine. The emergence of variant strains, especially delta and omicron, have also significantly reduced
vaccine efficacy. We propose
peptide vaccines as a potential
solution to address the inadequacies of the current
vaccines.
Peptide vaccines can be easily modified to target emerging strains, have greater stability, and do not require cold-chain storage. We screened five
peptide fragments (B1-B5) derived from the
SARS-CoV-2 spike protein to identify neutralizing B-cell
peptide antigens. We then investigated adjuvant systems for efficient stimulation of immune responses against the most promising
peptide antigens, including liposomal formulations of
polyleucine (L10) and polymethylacrylate (PMA), as well as classical adjuvants (CFA and
MF59). Immune efficacy of formulations was evaluated using competitive ELISA, pseudovirion neutralization, and live virus neutralization assays. Unfortunately,
peptide conjugation to L10 and PMA dramatically altered the secondary structure, resulting in low antibody neutralization efficacy. Of the
peptides tested, only B3 administered with CFA or
MF59 was highly immunogenic. Thus, a
peptide vaccine relying on B3 may provide an attractive alternative to currently marketed
vaccines.