Disparities in undergraduate STEM degree completions across the United States are a national concern. Undergraduate-level research opportunities are vital for developing future researchers and building their scientific identity. These experiences can help students in community colleges acquire 21st-century skills and build confidence in their ability to do science [1-3]. The development and implementation of guided research experiences provide users with a topic they are familiar with but not necessarily experts in, like SARS-CoV2 infections. In this particular study, the Immune Epitope Database (IEDB) was used to identify amino acid residues located on the immunogenic regions of the spike glycoprotein of SARS-CoV-2 variants: Alpha, Beta, Gamma, Delta, and Omicron. IEDB is a web-based bioinformatics tool that contains published epitope information and prediction aids that can be used as a research platform for studying infectious diseases. The objective of this study aimed to map the immunogenic regions on the spike glycoproteins of the SARS-CoV-2 variants and predict the immune evasion of these variants [4-6]. Identifying the antigenic determinations that bind to the antibodies is essential for designing future candidates for peptide-based vaccines.
This study aims to map the immunogenic regions on the spike glycoproteins of the SARS-CoV-2 variants and predict the immune evasion of these variants [4-6]. Identifying the antigenic determinations that bind to the antibodies is essential for designing future candidates for peptide-based vaccines. This research identifies regions where mutations have occurred in the virus, which are important to study as they can affect the virus's immune evasion and impact available vaccines. Targeting multiple immunogenic regions unaffected by mutations can serve as potential targets for new vaccines, providing better protection against different variants.
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This content will become publicly available on August 18, 2024
Mapping Immunogenic Regions In SARS-CoV-2 to Understand Vaccine Design Using Bioinformatics
Disparities in undergraduate STEM degree completions across the United States are a national concern. Undergraduate-level research opportunities are vital for developing future researchers and building their scientific identity. These experiences can help students in community colleges acquire 21st-century skills and build confidence in their ability to do science [1-3]. The development and implementation of guided research experiences provide users with a topic they are familiar with but not necessarily experts in, like SARS-CoV2 infections. In this particular study, the Immune Epitope Database (IEDB) was used to identify amino acid residues located on the immunogenic regions of the spike glycoprotein of SARS-CoV-2 variants: Alpha, Beta, Gamma, Delta, and Omicron. IEDB is a web-based bioinformatics tool that contains published epitope information and prediction aids that can be used as a research platform for studying infectious diseases. The objective of this study aimed to map the immunogenic regions on the spike glycoproteins of the SARS-CoV-2 variants and predict the immune evasion of these variants [4-6]. Identifying the antigenic determinations that bind to the antibodies is essential for designing future candidates for peptide-based vaccines.
This study aims to map the immunogenic regions on the spike glycoproteins of the SARS-CoV-2 variants and predict the immune evasion of these variants [4-6]. Identifying the antigenic determinations that bind to the antibodies is essential for designing future candidates for peptide-based vaccines. This research identifies regions where mutations have occurred in the virus, which are important to study as they can affect the virus’s immune evasion and impact available vaccines. Targeting multiple immunogenic regions unaffected by mutations can serve as potential targets for new vaccines, providing better protection against different variants.
more »
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- Award ID(s):
- 2055036
- NSF-PAR ID:
- 10454099
- Editor(s):
- Kazarinoff, P.
- Date Published:
- Journal Name:
- Journal of advanced technological education
- Volume:
- 2
- Issue:
- 2
- ISSN:
- 2832-9627
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract The continued emergence of new SARS‐CoV‐2 variants has accentuated the growing need for fast and reliable methods for the design of potentially neutralizing antibodies (Abs) to counter immune evasion by the virus. Here, we report on the de novo computational design of high‐affinity Ab variable regions (Fv) through the recombination of VDJ genes targeting the most solvent‐exposed hACE2‐binding residues of the SARS‐CoV‐2 spike receptor binding domain (RBD) protein using the software tool
OptMAVEn‐2.0 . Subsequently, we carried out computational affinity maturation of the designed variable regions through amino acid substitutions for improved binding with the target epitope. Immunogenicity of designs was restricted by preferring designs that match sequences from a 9‐mer library of “human Abs” based on a human string content score. We generated 106 different antibody designs and reported in detail on the top five that trade‐off the greatest computational binding affinity for the RBD with human string content scores. We further describe computational evaluation of the top five designs produced byOptMAVEn‐2.0 using a Rosetta‐based approach. We used RosettaSnugDock for local docking of the designs to evaluate their potential to bind the spike RBD and performed “forward folding” withDeepAb to assess their potential to fold into the designed structures. Ultimately, our results identified one designed Ab variable region, P1.D1, as a particularly promising candidate for experimental testing. This effort puts forth a computational workflow for the de novo design and evaluation of Abs that can quickly be adapted to target spike epitopes of emerging SARS‐CoV‐2 variants or other antigenic targets. -
The COVID-19 pandemic caused by SARS-CoV-2 sparked intensive research into the development of effective vaccines, 50 of which have been approved thus far, including the novel mRNA-based vaccines developed by Pfizer and Moderna. Although limiting the severity of the disease, the mRNA-based vaccines presented drawbacks, such as the cold chain requirement. Moreover, antibody levels generated by these vaccines decline significantly after 6 months. These vaccines deliver mRNA encoding the full-length spike (S) glycoprotein of SARS-CoV-2, but must be updated as new strains and variants of concern emerge, creating a demand for adjusted formulations and booster campaigns. To overcome these challenges, we have developed COVID-19 vaccine candidates based on the highly conserved SARS CoV-2, 809-826 B-cell peptide epitope (denoted 826) conjugated to cowpea mosaic virus (CPMV) nanoparticles and bacteriophage Qβ virus-like particles, both platforms have exceptional thermal stability and facilitate epitope delivery with inbuilt adjuvant activity. We evaluated two administration methods: subcutaneous injection and an implantable polymeric scaffold. Mice received a prime–boost regimen of 100 μg per dose (2 weeks apart) or a single dose of 200 μg administered as a liquid formulation, or a polymer implant. Antibody titers were evaluated longitudinally over 50 weeks. The vaccine candidates generally elicited an early Th2-biased immune response, which stimulates the production of SARS-CoV-2 neutralizing antibodies, followed by a switch to a Th1-biased response for most formulations. Exceptionally, vaccine candidate 826-CPMV (administered as prime-boost, soluble injection) elicited a balanced Th1/Th2 immune response, which is necessary to prevent pulmonary immunopathology associated with Th2 bias extremes. While the Qβ-based vaccine elicited overall higher antibody titers, the CPMV-induced antibodies had higher avidity. Regardless of the administration route and formulation, our vaccine candidates maintained high antibody titers for more than 50 weeks, confirming a potent and durable immune response against SARS-CoV-2 even after a single dose.more » « less
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Abstract SARS-CoV-2 worldwide spread and evolution has resulted in variants containing mutations resulting in immune evasive epitopes that decrease vaccine efficacy. We acquired SARS-CoV-2 positive clinical samples and compared the worldwide emerged spike mutations from Variants of Concern/Interest, and developed an algorithm for monitoring the evolution of SARS-CoV-2 in the context of vaccines and monoclonal antibodies. The algorithm partitions logarithmic-transformed prevalence data monthly and Pearson’s correlation determines exponential emergence of amino acid substitutions (AAS) and lineages. The SARS-CoV-2 genome evaluation indicated 49 mutations, with 44 resulting in AAS. Nine of the ten most worldwide prevalent (>70%) spike protein changes have Pearson’s coefficient r > 0.9. The tenth, D614G, has a prevalence >99% and r -value of 0.67. The resulting algorithm is based on the patterns these ten substitutions elucidated. The strong positive correlation of the emerged spike protein changes and algorithmic predictive value can be harnessed in designing vaccines with relevant immunogenic epitopes. Monitoring, next-generation vaccine design, and mAb clinical efficacy must keep up with SARS-CoV-2 evolution, as the virus is predicted to remain endemic.more » « less
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Site specific N- and O-glycosylation mapping of the spike proteins of SARS-CoV-2 variants of concernmore » « less
Abstract The glycosylation on the spike (S) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, modulates the viral infection by altering conformational dynamics, receptor interaction and host immune responses. Several variants of concern (VOCs) of SARS-CoV-2 have evolved during the pandemic, and crucial mutations on the S protein of the virus have led to increased transmissibility and immune escape. In this study, we compare the site-specific glycosylation and overall glycomic profiles of the wild type Wuhan-Hu-1 strain (WT) S protein and five VOCs of SARS-CoV-2: Alpha, Beta, Gamma, Delta and Omicron. Interestingly, both N- and O-glycosylation sites on the S protein are highly conserved among the spike mutant variants, particularly at the sites on the receptor-binding domain (RBD). The conservation of glycosylation sites is noteworthy, as over 2 million SARS-CoV-2 S protein sequences have been reported with various amino acid mutations. Our detailed profiling of the glycosylation at each of the individual sites of the S protein across the variants revealed intriguing possible association of glycosylation pattern on the variants and their previously reported infectivity. While the sites are conserved, we observed changes in the N- and O-glycosylation profile across the variants. The newly emerged variants, which showed higher resistance to neutralizing antibodies and vaccines, displayed a decrease in the overall abundance of complex-type glycans with both fucosylation and sialylation and an increase in the oligomannose-type glycans across the sites. Among the variants, the glycosylation sites with significant changes in glycan profile were observed at both the
N -terminal domain and RBD of S protein, with Omicron showing the highest deviation. The increase in oligomannose-type happens sequentially from Alpha through Delta. Interestingly, Omicron does not contain more oligomannose-type glycans compared to Delta but does contain more compared to the WT and other VOCs. O-glycosylation at the RBD showed lower occupancy in the VOCs in comparison to the WT. Our study on the sites and pattern of glycosylation on the SARS-CoV-2 S proteins across the VOCs may help to understand how the virus evolved to trick the host immune system. Our study also highlights how the SARS-CoV-2 virus has conserved bothN - andO - glycosylation sites on the S protein of the most successful variants even after undergoing extensive mutations, suggesting a correlation between infectivity/ transmissibility and glycosylation.
