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Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice

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Abstract

The protective efficacies of current licensed vaccines against COVID-19 have significantly reduced as a result of SARS-CoV-2 variants of concern (VOCs) which carried multiple mutations in the Spike (S) protein. Considering that these vaccines were developed based on the S protein of the original SARS-CoV-2 Wuhan strain, we designed a recombinant plasmid DNA vaccine based on highly conserved and immunogenic B and T cell epitopes against SARS-CoV-2 Wuhan strain and the Omicron VOC. Literature mining and bioinformatics were used to identify 6 immunogenic peptides from conserved regions of the SARS-CoV-2 S and membrane (M) proteins. Nucleotide sequences encoding these peptides representing highly conserved B and T cell epitopes were cloned into a pVAX1 vector to form the pVAX1/S2-6EHGFP recombinant DNA plasmid vaccine. The DNA vaccine was intranasally or intramuscularly administered to BALB/c mice and evaluations of humoral and cellular immune responses were performed. The intramuscular administration of pVAX1/S2-6EHGFP was associated with a significantly higher percentage of CD8+ T cells expressing IFN-γ when compared with the empty vector and PBS controls. Intramuscular or intranasal administrations of pVAX1/S2-6EHGFP resulted in robust IgG antibody responses. Sera from mice intramuscularly immunized with pVAX1/S2-6EHGFP were found to elicit neutralizing antibodies capable of SARS-CoV-2 Omicron variant with the ACE2 cell surface receptor. This study demonstrated that the DNA vaccine construct encoding highly conserved immunogenic B and T cell epitopes was capable of eliciting potent humoral and cellular immune responses in mice.

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Data Availability

The authors confirm that the data supporting the findings of the study are available within the article and its Supplementary section. Raw data that support the findings of the study are available from the corresponding author, upon reasonable request. 

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Funding

This research was funded by Sunway University Research Grants 2021 (GRTIN-RF-01-2021) and Sunway University Internal Grant Scheme 2023 (GRTIN-IGS(02)-CVVR-11-2023) to Chit Laa Poh and Hui Xuan Lim from the Centre for Virus and Vaccine Research (CVVR), School of Medical and Life Sciences, Sunway University. This study was also supported by Sunway University Internal Grant Scheme 2022 (GRTIN-IGS(02)-DBS-10-2022) to Ayaz Anwar from Department of Biological Science, School of Medical and Life Sciences, Sunway University.

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Authors and Affiliations

  1. Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia

    Kanwal Khalid, Hui Xuan Lim & Chit Laa Poh

  2. Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia

    Ayaz Anwar & Seng-Kai Ong

  3. Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Soon Hao Tan

  4. Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia

    Jung Shan Hwang

  5. Sunway Microbiome Centre, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia

    Hui Xuan Lim

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  1. Kanwal Khalid
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Contributions

Conceptualization, K.K., H.X.L., and C.L.P.; data analysis, K.K. and H.X.L.; investigation, K.K., H.X.L., T.S.H.; writing original draft, K.K.; review and editing, K.K., H.X.L., A.A., H.J.S., O.S.K., and C.L.P.; supervision C.L.P. All authors have read and agreed to the published version of the manuscript.

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Khalid, K., Lim, H.X., Anwar, A. et al. Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice. AAPS PharmSciTech 25, 60 (2024). https://doi.org/10.1208/s12249-024-02778-x

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