Preclinical Development of a Novel Epitope-based DNA Vaccine Candidate against SARS-CoV-2 and Evaluation of Immunogenicity in BALB/c Mice.
- Resource Type
- Academic Journal
- Authors
- Khalid K; Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.; Lim HX; Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.; Sunway Microbiome Centre, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.; Anwar A; Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.; Tan SH; Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.; Hwang JS; Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.; Ong SK; Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia.; Poh CL; Centre for Virus and Vaccine Research, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Petaling Jaya, Selangor, Malaysia. chitlaa.poh@gmail.com.
- Source
- Publisher: Springer Country of Publication: United States NLM ID: 100960111 Publication Model: Electronic Cited Medium: Internet ISSN: 1530-9932 (Electronic) Linking ISSN: 15309932 NLM ISO Abbreviation: AAPS PharmSciTech Subsets: MEDLINE
- Subject
- Language
- English
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.
(© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)