Coronavirus disease 2019 (COVID-19) is the greatest threat to global health at the present time, and considerable public and private effort is being devoted to fighting this recently emerged disease. Despite the undoubted advances in the development of
vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of
COVID-19, uncertainty remains about their future efficacy and the duration of the immunity induced. It is therefore prudent to continue designing and testing
vaccines against this pathogen. In this article we computationally designed two candidate
vaccines, one monopeptide and one multipeptide, using a technique involving optimizing lambda-superstrings, which was introduced and developed by our research group. We tested the monopeptide
vaccine, thus establishing a proof of concept for the validity of the technique. We synthesized a
peptide of 22
amino acids in length, corresponding to one of the candidate
vaccines, and prepared a dendritic cell (DC)
vaccine vector loaded with the 22
amino acids SARS-CoV-2 peptide (positions 50-71) contained in the NTD domain (DC-CoVPSA) of the Spike
protein. Next, we tested the immunogenicity, the type of immune response elicited, and the
cytokine profile induced by the
vaccine, using a non-related bacterial
peptide as negative control. Our results indicated that the CoVPSA
peptide of the Spike
protein elicits noticeable immunogenicity in vivo using a DC
vaccine vector and remarkable cellular and humoral immune responses. This DC
vaccine vector loaded with the NTD
peptide of the Spike
protein elicited a predominant Th1-Th17
cytokine profile, indicative of an effective anti-viral response. Finally, we performed a proof of concept experiment in humans that included the following groups: asymptomatic non-active
COVID-19 patients, vaccinated volunteers, and control donors that tested negative for SARS-CoV-2. The positive control was the current receptor binding domain
epitope of
COVID-19 RNA-vaccines. We successfully developed a
vaccine candidate technique involving optimizing lambda-superstrings and provided proof of concept in human subjects. We conclude that it is a valid method to decipher the best
epitopes of the Spike
protein of SARS-CoV-2 to prepare
peptide-based
vaccines for different vector platforms, including DC
vaccines.