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1. Mapping Immunogenic Regions In SARS-CoV-2 to Understand Vaccine Design Using Bioinformatics

   https://doi.org/10.5281/zenodo.8260361  

   Sanchez Rocha, Joanna A.; Anderson, Brady; Morales, Jatniel; Salgado, Christopher; Smith, Cidney; Jarjapu, Mahita; Mendes, Marcus; Blazeska, Nina; Vemu, Sheela (January 2023, Journal of advanced technological education)

   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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2. Dynamic SARS-CoV-2 emergence algorithm for rationally-designed logical next-generation vaccines

   https://doi.org/10.1038/s42003-022-04030-3  

   Maison, David P.; Ching, Lauren L.; Cleveland, Sean B.; Tseng, Alanna C.; Nakano, Eileen; Shikuma, Cecilia M.; Nerurkar, Vivek R. (December 2022, Communications Biology)

   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. 

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3. COVID-19 vaccines based on viral nanoparticles displaying a conserved B-cell epitope show potent immunogenicity and a long-lasting antibody response

   https://doi.org/10.3389/fmicb.2023.1117494  

   Affonso de Oliveira, Jessica Fernanda; Zhao, Zhongchao; Xiang, Yi; Shin, Matthew D.; Villaseñor, Kathleen Elizabeth; Deng, Xinyi; Shukla, Sourabh; Chen, Shaochen; Steinmetz, Nicole F. (April 2023, Frontiers in Microbiology)

   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. 

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4. Point mutations in SARS-CoV-2 variants induce long-range dynamical perturbations in neutralizing antibodies

   https://doi.org/10.1039/D2SC00534D  

   Ray, Dhiman; Quijano, Riley Nicolas; Andricioaei, Ioan (June 2022, Chemical Science)

   Mutations in the new variants of SARS-CoV-2 spike protein modulates the dynamics of the neutralizing antibodies. Capturing such modulations from MD simulations and graph network model identifies the role of mutations in facilitating immune evasion. 

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5. Genetic and Structural Analysis of SARS-CoV-2 Spike Protein for Universal Epitope Selection

   https://doi.org/10.1093/molbev/msac091  

   Markosian, Christopher; Staquicini, Daniela I.; Dogra, Prashant; Dodero-Rojas, Esteban; Lubin, Joseph H.; Tang, Fenny H.F.; Smith, Tracey L.; Contessoto, Vinícius G.; Libutti, Steven K.; Wang, Zhihui; et al (May 2022, Molecular Biology and Evolution)

   Ozkan, Banu (Ed.)

   Abstract Evaluation of immunogenic epitopes for universal vaccine development in the face of ongoing SARS-CoV-2 evolution remains a challenge. Herein, we investigate the genetic and structural conservation of an immunogenically relevant epitope (C662–C671) of spike (S) protein across SARS-CoV-2 variants to determine its potential utility as a broad-spectrum vaccine candidate against coronavirus diseases. Comparative sequence analysis, structural assessment, and molecular dynamics simulations of C662–C671 epitope were performed. Mathematical tools were employed to determine its mutational cost. We found that the amino acid sequence of C662–C671 epitope is entirely conserved across the observed major variants of SARS-CoV-2 in addition to SARS-CoV. Its conformation and accessibility are predicted to be conserved, even in the highly mutated Omicron variant. Costly mutational rate in the context of energy expenditure in genome replication and translation can explain this strict conservation. These observations may herald an approach to developing vaccine candidates for universal protection against emergent variants of coronavirus. 

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