First computational design using lambda-superstrings and in vivo validation of SARS-CoV-2 vaccine

Abstract

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.

Testing a vaccine candidate against Hepatitis C virus designed by combinatorial optimization

“…However, although we targeted HCV, the methodology presented here can be used against other viruses (preferably those with high variability), such as influenza 15 , HIV 16 , or SARS CoV-2 30 .…”

Computational Protein Design for COVID-19 Research and Emerging Therapeutics

“…Martínez et al described an algorithm that used optimized λ-superstrings to computationally design monopeptide and multipeptide SARS-CoV-2 vaccine candidates. They combined a 22-mer peptide derived from the N-terminal domain (NTD) of the SARS-CoV-2 spike protein with a dendritic cell vector to elicit remarkable cellular and humoral immune responses; these candidate vaccines conferred a protective response in human subjects through the induction of high levels of SARS-CoV-2 neutralizing IgGs. , Computational techniques enable the development of effective and rapid diagnostics for infectious diseases. Hajikarimlou and co-workers recently used the In Silico Protein Synthesizer (InSiPS) computational approach to aid in the design of the rapid peptide that binds SARS-CoV-2 spike protein at the RBD or the S1/S2 region, shedding more light on the field of peptide diagnostics for COVID-19 study .…”

“…61 of high levels of SARS-CoV-2 neutralizing IgGs. 66,67 Computational techniques enable the development of effective and rapid diagnostics for infectious diseases. Hajikarimlou and co-workers recently used the In Silico Protein Synthesizer (InSiPS) computational approach to aid in the design of the rapid peptide that binds SARS-CoV-2 spike protein at the RBD or the S1/S2 region, shedding more light on the field of peptide diagnostics for COVID-19 study.…”

Unlocking the Potential of In-silico Approaches: Drug Development and Vaccine Design

“…Epitope prediction has become crucial in identifying the epitopes that can activate T and B cell responses. 36,37 An epitope, also known as an antigenic determinant, is an exposed surface area of an antigen that, upon binding an antibody, elicits an immune response. Specific antibodies (Abs) recognize antigenic determinants, which are discrete regions of an antigen (Ag).…”