key: cord-0708511-abk51xpr authors: Lim, Hui Xuan; Lim, Jianhua; Jazayeri, Seyed Davoud; Poppema, Sibrandes; Poh, Chit Laa title: Development of multi-epitope peptide-based vaccines against SARS-CoV-2 date: 2020-10-01 journal: Biomed J DOI: 10.1016/j.bj.2020.09.005 sha: ea573c48d161cbd721b2ff968d36fc9d2d7f751c doc_id: 708511 cord_uid: abk51xpr Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic involving so far more than 15 million infections and 630,211 deaths. Effective vaccines are urgently needed to prevent SARS-CoV-2 infections. No vaccines have yet been approved for licensure by regulatory agencies. Even though host immune responses to SARS-CoV-2 infections are beginning to be unravelled, effective clearance of virus will depend on both humoral and cellular immunity. Additionally, the presence of Spike (S)-glycoprotein reactive CD4+ T-cells in the majority of convalescent patients is consistent with its significant role in stimulating B and CD8+ T-cells. The search for immunodominant epitopes relies on experimental evaluation of peptides representing the epitopes from overlapping peptide libraries which can be costly and labor-intensive. Recent advancements in B- and T-cell epitope predictions by bioinformatic analysis have led to epitope identifications. Assessing which peptide epitope can induce potent neutralizing antibodies and robust T-cell responses is a prerequisite for the selection of effective epitopes to be incorporated in peptide-based vaccines. This review discusses the roles of B- and T-cells in SARS-CoV-2 infections and experimental validations for the selection of B-, CD4+ and CD8+ T-cell epitopes which could lead to the construction of a multi-epitope peptide vaccine. Peptide-based vaccines are known for their low immunogenicity which could be overcome by incorporating immunostimulatory adjuvants and nanoparticles such as Poly Lactic-co-Glycolic Acid (PLGA) or chitosan. reported to lead to pneumonia, acute respiratory distress syndrome, acute cardiac injury 28 and death [1] . The genome size of the SARS-CoV-2 is approximately 29.9 kb and its 29 genome structure is homologous to SARS-CoV-1. The 5' region consists of two-thirds of 30 the genome, comprising the orf1ab that encodes the orf1ab polyprotein, while the 31 3′region is composed of one-third of the genome encoding structural proteins which 32 include surface (S), envelope (E), membrane (M), and nucleocapsid (N) proteins. 33 Additionally, the SARS-CoV-2 virus contains 6 accessory proteins: ORF1ab, NS3, NS6, 34 NS7a, NS7b, and NS8 [2] . Table 1 . 58 J o u r n a l P r e -p r o o f The production of epitope-specific antibodies is a primary mechanism of protection CoV-2 S peptide library, pools S14 and S21, were strongly recognized by sera from 349 COVID-19 patients [43] . In an effort to select promising T-cell epitopes that were predicted by bioinformatics, 351 CD4+ and CD8+ T-cell epitopes that were predicted to be present in the spike (S) 352 protein of SARS-CoV-2 from a total of 11 different publications were compared (Table J o u r n a l P r e -p r o o f Some of the epitopes presented in Table 5 can be observed to overlap with epitopes 355 from Tables 2 and 3 , further confirming that the predicted T-cell epitopes are promising 356 epitopes that bind to MHC class I and II molecules. A few potential epitopes that 357 represent B-and T-cell epitopes from the S protein were identified after amalgamating 358 information gathered from Tables 2, 3, 4, 5 and are presented in Table 6 . Epitope Table 4 . All of the epitopes listed in Table 4 T-cell epitope prediction servers such as the IEDB T-cell CoV. This would help to locate highly conserved epitopes that could be used for No ethical statement is needed since this is a review paper. 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