Design of peptide vaccine for SARS-CoV-2

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 trigger 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.
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.
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.”

*Important Notice

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.

Journal reference:
Susha Cheriyedath

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.

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