Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an unprecedented global pandemic challenging public health and leading to a dramatic loss of human lives worldwide. Therefore, it is crucial to understand which SARS-CoV-2-specific epitopes can induce a T cell response and offer protection to a broad population 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, researchers from the US identified two immunogenic non-structural proteins – PLpro and RdRp – from immunodominant gene regions ORF1ab, ORF3a and ORF9b as potential targets for a vaccine against SARS-CoV-2.
“ORF3a protein, known for the suppression of innate immune response, was also predicted to have a high number of T cell epitopes for an effective vaccine design.”
The researchers used several different clinical properties including allergenicity, antigenicity, IFN-y secretion, and toxicity in order to select top epitopes for vaccine design. This study is currently available on the bioRxiv* preprint server while awaiting peer review.
Multiple potential vaccine constructs that could cover a high percentage of world population
Their analysis of CD8 and CD4 T cell epitopes showed the presence of multiple potential vaccine constructs that cover a high proportion of the global population. They identified eight immunogenic, non-allergenic, antigenic, stable, non-toxic, and IFN-y inducing CD8 proteins for nsp3, 11 for ORF3a, 4 for nsp12, and 3 for ORF9b. These proteins are common across 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 global population, respectively.
“We identified 5 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing nsp3 CD8 epitopes with at least weak affinity to one or more mouse MHC alleles, 4 for nsp12 protein and 6 for ORF3a protein, all common to the studied VOC.”
They also identified variant-specific T cell epitopes that could help separately target each variant strain. The results predicted mouse MHC affinity towards the top CD8 epitopes. They revealed three immunogenic, antigenic, non-toxic, non-allergenic, stable and IFN-y inducing CD8 epitopes that overlap with 6 antigenic, non-allergenic, stable, non-toxic, and IFN-y inducing CD4 epitopes across the 4 variants of concern, which can be used in pre-clinical studies.
CD4+ and CD8+ T cell activation and response. Interaction between MHC molecules and T cell receptors (TCR) on T cells triggers the activation of CD4+ and CD8+ T cells that lead to the production of memory T and B cells. Cytokines and cytotoxic granules are released in response to a stimulus. The figure was created with BioRender.com.
Study reveals SARS-CoV-2 peptides from ORF proteins and multiple T cell epitopes that can help peptide-based SARS-CoV-2 vaccine development
Given the lack of effective antiviral treatments, there is a pressing need for an effective vaccine against various strains of SARS-CoV-2 and among different ethnic groups around the globe. This study sheds light on previously unclear SARS-CoV-2 HLA-I and HLA-II peptides from ORF proteins in the viral genome. In addition, it reveals multiple T cell epitopes that can help 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 from ORF3a and ORF9b proteins.”
In order to ensure the effectiveness of the vaccine construct against the most common SARS-CoV-2 mutations currently circulating across the globe, mutations from 4 lineages of SARS-CoV-2 variants of concern B.1.1.7, P.1, B.1.617.2, and B.1.351 were gathered and analyzed by the researchers.
The complete genome of SARS-CoV-2. The 5’ end consists of a large gene region ORF1ab and its non-structural proteins (nsp1-16). The 3’ end compromises the structural proteins (nucleocapsid, membrane, envelope, spike) and other open-reading-frame (ORF) proteins. The figure was created with BioRender.com.
They revealed 3 immunogenic, non-allergenic, antigenic, non-toxic, stable and IFN-y inducing CD8 epitopes that have an affinity to mouse MHC alleles and were present in at least one antigenic non-allergenic, stable, non-toxic, and IFN-y inducing CD4 epitope. Altogether they have the ability to induce a robust immune response and offer protection to 99.99% of the global population, which suggests its efficacy as a potential multi-epitope vaccine construct.
The landscape of SARS-CoV-2 T cell epitopes identified in this study can help SARS-CoV-2 vaccine development and future research on epitope-based peptide vaccines.
“These findings suggest that a single multi-epitope vaccine candidate should be efficacious against currently circulating lineages.”
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.