PMID- 34208061 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210714 IS - 2076-0817 (Print) IS - 2076-0817 (Electronic) IS - 2076-0817 (Linking) VI - 10 IP - 6 DP - 2021 Jun 11 TI - Multi-Epitope Vaccine Design Using an Immunoinformatic Approach for SARS-CoV-2. LID - 10.3390/pathogens10060737 [doi] LID - 737 AB - Through 4 June 2021, COVID-19 has caused over 172.84 million cases of infection and 3.71 million deaths worldwide. Due to its rapid dissemination and high mutation rate, it is essential to develop a vaccine harboring multiple epitopes and efficacious against multiple variants to prevent the immune escape of SARS-CoV-2. An in silico approach based on the viral genome was applied to identify 19 high-immunogenic B-cell epitopes and 499 human leukocyte antigen (HLA)-restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo-Suite and manufactured by solid-phase synthesis. Docking analysis confirmed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four peptide candidates derived from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of total IgG in serum, as well as an increase of CD19+ cells in the inguinal lymph nodes, were observed in the peptide-immunized mice compared to the control. The ratios of IFN-gamma-secreting lymphocytes in CD4+ or CD8+ T-cells in the peptide-immunized mice were higher than those in the control mice. There were also a larger number of IFN-gamma-secreting T-cells in the spleens of peptide-immunized mice. The peptide vaccines in this study successfully elicited antigen-specific humoral and cellular immune responses in mice. To further validate the safety and efficacy of this vaccine, animal studies using a primate model, as well as clinical trials in humans, are required. FAU - Feng, Ye AU - Feng Y AUID- ORCID: 0000-0002-6551-1560 AD - Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310001, China. AD - Institute for Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310002, China. FAU - Jiang, Haiping AU - Jiang H AUID- ORCID: 0000-0002-4394-6176 AD - The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310007, China. FAU - Qiu, Min AU - Qiu M AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. FAU - Liu, Liang AU - Liu L AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. FAU - Zou, Shengmei AU - Zou S AD - Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310001, China. AD - Institute for Translational Medicine, Zhejiang University School of Medicine, Hangzhou 310002, China. FAU - Li, Yun AU - Li Y AD - Zhejiang Forest Resources Monitoring Center, Hangzhou 310020, China. FAU - Guo, Qianpeng AU - Guo Q AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. FAU - Han, Ning AU - Han N AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. FAU - Sun, Yingqiang AU - Sun Y AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. FAU - Wang, Kui AU - Wang K AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. FAU - Lu, Lantian AU - Lu L AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. FAU - Zhuang, Xinlei AU - Zhuang X AD - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. FAU - Zhang, Shanshan AU - Zhang S AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. AD - Zhejiang California International Nanosystems Institute, Zhejiang University, Hangzhou 310058, China. FAU - Chen, Shuqing AU - Chen S AUID- ORCID: 0000-0002-0792-3735 AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. AD - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. AD - Zhejiang California International Nanosystems Institute, Zhejiang University, Hangzhou 310058, China. FAU - Mo, Fan AU - Mo F AD - Hangzhou Neoantigen Therapeutics Co., Ltd., Hangzhou 310058, China. AD - College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. AD - Vancouver Prostate Centre, University of British Columbia, Vancouver, BC V6H 3Z6, Canada. AD - Hangzhou AI-Force Therapeutics Co., Ltd., Hangzhou 310000, China. LA - eng GR - KWJ-ZJ-2108/National Health and Family Planning Commission Research Fund & Zhejiang Provincial Medical and Health Major Science and Technology Plan Project/ GR - LGF20E030004/Public Welfare Technology Application Research Project of Zhejiang Province/ PT - Journal Article DEP - 20210611 PL - Switzerland TA - Pathogens JT - Pathogens (Basel, Switzerland) JID - 101596317 PMC - PMC8230658 OTO - NOTNLM OT - COVID-19 OT - SARS-CoV-2 OT - epitope OT - immunoinformatics OT - peptide OT - vaccine COIS- The authors declare that they have no conflict of interests. EDAT- 2021/07/03 06:00 MHDA- 2021/07/03 06:01 PMCR- 2021/06/11 CRDT- 2021/07/02 01:33 PHST- 2021/04/03 00:00 [received] PHST- 2021/06/04 00:00 [revised] PHST- 2021/06/08 00:00 [accepted] PHST- 2021/07/02 01:33 [entrez] PHST- 2021/07/03 06:00 [pubmed] PHST- 2021/07/03 06:01 [medline] PHST- 2021/06/11 00:00 [pmc-release] AID - pathogens10060737 [pii] AID - pathogens-10-00737 [pii] AID - 10.3390/pathogens10060737 [doi] PST - epublish SO - Pathogens. 2021 Jun 11;10(6):737. doi: 10.3390/pathogens10060737.