A vaccine to prevent infection with SARS-CoV-2 is regarded as the most effective way to halt the COVID-19 pandemic. A major vaccine strategy is to prevent interaction between the receptor binding domain (RBD) of the Spike protein and the angiotensin converting enzyme-2 (ACE2) receptor on lung epithelial cells and on other cells. These vaccines will also induce T-cell responses, which may play a role in protection. However, concerns were raised that aberrant vaccine-induced immune responses may exacerbate disease, as has been shown to occur in other viruses, including some coronaviruses. We identified minimal epitopes on the RBD that would induce antibody responses that block the interaction of the RBD and ACE2 as a strategy that would lead to an effective vaccine with reduced likelihood of inducing immunopathology.
We tested convalescent plasma for their ability to neutralize SARS-CoV-2. We procured a series of overlapping linear peptides spanning the RBD and asked which of these were recognized by plasma from COVID-19 convalescent patients. Identified peptide epitopes were then conjugated to a carrier protein and used to vaccinate mice. Immune sera were tested for binding to the RBD and for their ability to compete with the interaction of the RBD and ACE2. We identified seven putative peptide epitopes of which three induced antibodies that could partially block the interaction of the RBD and ACE2 individually. Antibody titres did not diminish over 3 months. Two of the peptides were located in the two main regions of the RBD known to contact ACE2. Epitope-specific memory B-cells (MBCs) found in the blood of convalescent patients corelated and with epitope-specific antibody responses. Taken together, the data demonstrate that COVID-19 convalescent patients have SARS-CoV-2-specific antibodies and MBCs, the specificities of which can be defined with short peptides. This approach will aid the design of a vaccine containing only minimal antigenic material, thus improving the vaccine’s safety profile.