Design of a peptide vaccine against SARS-CoV-2



The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused an unprecedented global pandemic endangering public health and causing dramatic loss of life around the world. Therefore, understanding which epitopes specific to SARS-CoV-2 can induce a T cell response and provide protection to a large population is crucial to design a vaccine against the novel coronavirus.

Immunogenic non-structural proteins as potential targets for a SARS-CoV-2 vaccine

In a recent study, US researchers identified two non-structural immunogenic proteins – PLpro and RdRp – immunodominant genetic regions ORF1ab, ORF3a and ORF9b as potential targets for a vaccine against SARS-CoV-2.

“The ORF3a protein, known to suppress the innate immune response, should also have a high number of T cell epitopes for effective vaccine design.”

The researchers used several different clinical properties including allergenicity, antigenicity, IFN-γ secretion, and toxicity to select the best epitopes for vaccine design. This study is currently available on the bioRxiv* preprint server pending peer review.

Several potential vaccine constructs that could cover a high percentage of the world’s population

Their analysis of CD8 and CD4 T cell epitopes showed the presence of several potential vaccine constructs that cover a high proportion of the world’s population. They identified eight immunogenic, non-allergenic, antigenic, stable, non-toxic and IFN-γ-inducing CD8 proteins for nsp3, 11 for ORF3a, 4 for nsp12 and 3 for ORF9b. These proteins are common to four variants of concern, namely B.1.1.7, P.1, B.1.351 and B.1.617.2, and protect 98.12%, 87.08%, 96.07% and 63, 8% of the world’s population, respectively.

“We identified 5 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-γ-inducing nsp3 CD8 epitopes with at least low affinity for one or more mouse MHC alleles, 4 for the nsp12 protein and 6 for the ORF3a protein, all currents at the VOC studied.

They also identified variant-specific T cell epitopes that could help target each variant strain separately. The results predicted the affinity of mouse MHC towards higher CD8 epitopes. They revealed three immunogenic, antigenic, non-toxic, non-allergenic, stable and IFN-γ-inducing CD8 epitopes which overlapped with 6 antigenic, non-allergenic, stable, non-toxic CD4 epitopes and IFN-γ inducing in the 4 variants. of concern, which can be used in preclinical studies.

Activation and response of CD4 + and CD8 + T lymphocytes. The interaction between MHC molecules and T cell receptors (TCRs) on T cells triggers the activation of CD4 + and CD8 + T cells which lead to the production of T and B memory cells. Cytokines and cytotoxic granules are released in response to a stimulus. The figurine was created with BioRender.com.

Study reveals SARS-CoV-2 peptides from ORF proteins and multiple T cell epitopes that may aid in development of peptide-based SARS-CoV-2 vaccine

Given the lack of effective antiviral treatments, there is an urgent need for an effective vaccine against various strains of SARS-CoV-2 and among different ethnic groups around the world. This study sheds light on previously unclear SARS-CoV-2 HLA-I and HLA-II peptides of ORF proteins in the viral genome. In addition, it reveals several T cell epitopes that may aid in the development of peptide-based vaccines against SARS-CoV-2.

“We predicted CD4 and CD8 T cell epitopes for two non-structural proteins, nsp3 and nsp12, as well as proteins ORF3a and ORF9b.”

In order to ensure the efficacy of the vaccine construct against the most common SARS-CoV-2 mutations currently circulating in the world, the mutations of 4 lines of SARS-CoV-2 variants of concern B.1.1.7, P .1, B .1.617.2 and B.1.351 were collected and analyzed by the researchers.

The complete SARS-CoV-2 genome.  The 5 'end consists of a large ORF1ab gene region and its non-structural proteins (nsp1-16).  The 3 'end compromises structural proteins (core, membrane, envelope, tip) and other open reading frame (ORF) proteins.  The figurine was created with BioRender.com.

The complete SARS-CoV-2 genome. The 5 ‘end consists of a large ORF1ab gene region and its non-structural proteins (nsp1-16). The 3 ‘end compromises structural proteins (core, membrane, envelope, tip) and other open reading frame (ORF) proteins. The figurine was created with BioRender.com.

They revealed 3 immunogenic, non-allergenic, antigenic, non-toxic, stable and IFN-γ-inducing CD8 epitopes which have affinity for mouse MHC alleles and were present in at least one non-allergenic, stable, non-toxic antigen. and CD4 epitope inducing IFN-γ. In total, they have the ability to induce a robust immune response and offer protection to 99.99% of the world’s population, suggesting its efficacy as a potential multi-epitope vaccine construct.

The SARS-CoV-2 T cell epitope landscape identified in this study may aid in the development of the SARS-CoV-2 vaccine and future research into epitope-based peptide vaccines.

“These results suggest that a single multi-epitope vaccine candidate should be effective against the lines currently in circulation.”

*Important Notice

bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.


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