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. 2020 Feb 24;17(5):539–540. doi: 10.1038/s41423-020-0377-z

Epitopes for a 2019-nCoV vaccine

Guglielmo Lucchese 1,
PMCID: PMC7091830  PMID: 32094505

After causing an initial cluster of Pneumonia in Wuhan City, Hubei Province, the 2019-nCoV has quickly spread through South East Asia and within a few weeks to Europe, Africa, and America. Initial estimates suggested a mortality rate of 2% and that ~18% of the cases show severe symptoms, although such estimates are still subject to rapid changes (https://www.who.int/news-room/detail/30-01-2020-statement-on-the-second-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-outbreak-of-novel-coronavirus-(2019-ncov)).13

To facilitate the swift development of a candidate vaccine for 2019-nCoV we compared here the viral and the human proteomes, searching for pentapeptides that are unique to the pathogen. We followed the rationale that non-self sequences are highly immunogenic and uniquely viral epitopes should improve safety and efficacy by minimizing the risk for cross-reactions and increasing anti-viral specificity.46 The analysis was conducted on the entire viral proteome but primarily focused on the surface spike glycoprotein (id = “QHD43416.1) because immune response against it is highly likely to exert a neutralizing effect.2

The entire amino acid (aa) sequence of the 2019-nCoV was retrieved from https://www.ncbi.nlm.nih.gov/nuccore/MN908947 and dissected into pentapeptides overlapped by four residues for a total of n = 9661. Then, each pentamer was analyzed for occurrences in the human proteome using the Peptide Match program (https://research.bioinformatics.udel.edu/peptidematch/index.jsp).7

It resulted that n = 933 viral pentapeptides are absent in the human proteome, and therefore foreign to the human immune system (Table S1). Among these non-self pentapeptides, n = 107 are embedded in the viral surface glycoprotein (spike protein) that mediates binding to the human ACE2 and cellular entry.2

The recommended oligopeptides for a multi-epitope 2109-nCoV-vaccine are presented in Table 1, Panel a. They can be rapidly tested in animal models for immunogenicity and safety in order to timely develop a vaccine for preventing uncontrolled spreading of the novel coronavirus.

Table 1.

(a) Oligopeptides (n = 73) of the spike protein absent in the human proteome to be tested for a potential vaccine. Contiguous pentapeptides with a four residue overlap were considered as a single, longer oligopeptidic sequence; the length of each of these oligopeptides was dictated by the extension of the overlap. Oligopeptides from epitopes in panel b are in bold. (b) Experimentally validated epitopes (n = 66) containing at least one of the 107 pentapeptides (capitalized) of the spike protein that are absent in the human proteome

(a) RGVYYPDK, NVTWFHA, FHAIH, PFNDG, IRGWIF, IFGTT, VCEFQFC, CNDPF, VYYHK, NNKSW, NKSWM, WMESEF, YSSAN, CTFEY, GNFKN, GYFKI, IYSKHT, PIGIN, GWTAG, AYYVG, NENGT, SETKC, GIYQT, VYAWNR, CVADY, STFKC, FKCYGVS, TNVYA, IADYN, DYNYKL, VIAWN, AWNSNN, STPCN, PCNGV, GFNCYF, QSYGF, VKNKC, NKCVN, CVNFN, CTEVP, IGAEH, YQTQTN, IAYTMS, TSVDC, DCTMY, TMYICG, DSTEC, FCTQL, PIKDF, QYGDCL, GDCLG, DLICAQKF, MIAQY, SGWTF, WTFGA, FAMQM, MQMAYRF, RFNGI, MSECV, GYHLMS, KNFTT, PAICH, NGTHWFVTQ, TQRNF, NFYEP, IGIVN, NTVYD, IKWPWYI, YIWLGF, IAIVM, LCCMTS, MTSCC, CCKFD
(b) IEDB-ID-Number Epitope
307 aalvsgtatagWTFGAg
462 aatkMSECVlgqskrvd
1460 agclIGAEHvdtsyecd
3176 aMQMAYRF
6011 canlllqygsFCTQLnralsgia
6333 cgpklstdliknqCVNFNfngltgtgvltpsskrfqpfqqfg
6334 cgpklstdliknqCVNFNfngltgtgvltpsskrfqpfqqfgrdvsdftd
7066 csqnplaelkcsvksfeidkGIYQTsnfrvvpsgd
7217 cttfddvqapnytqhtssmRGVYYPDeifr
7383 CYGVSatklndlcfsnv
8239 dfcgkGYHLMSfpqaap
12417 eidkGIYQTsnfrvvps
15903 ffSTFKCYGVSatklnd
18161 fvfngtswfiTQRNFfs
18515 gaalqipFAMQMAYRFn
21464 gnliaprGYFKIrsgkssim
22321 gsFCTQLn
24978 htssmRGVYYPDeifrs
25250 IADYNYKLpddfmgcvl
25293 iaglIAIVMvtillccm
25378 iapgqtgvIADYNYKLp
25382 iaprGYFKIrngkssimrsdapigtcssecit
29728 iywtivkpgdillinstgnliaprGYFKIrn
30987 kGIYQTsn
30988 kGIYQTsnfrvvpsgdvvrf
31581 kkisnCVADYsvlynst
31582 kkisnCVADYsvlynstf
33305 ksfeidkGIYQTsnfrvv
33358 ksivAYTMSlgadssia
33874 kTSVDCnMYICGDSTEC
36579 liknqCVNFNfngltgt
36815 lkcsvksfeidkGIYQT
36856 lkgacscgsCCKFDedd
37758 llrstsqksivAYTMSl
39023 lqygsFCTQLnralsgi
41177 MAYRFNGIgvtqnvlye
42999 mvtilLCCMTSCCsclk
43145 nafnCTFEYisdafsld
46379 nvfqtqagclIGAEHvd
46822 PAICHegkayfpregvfvfngtswfitqrnffs
47479 pFAMQMAYRFNGIgvtq
49968 pvsmakTSVDCnMYICGds
50058 pwyvwlgfiaglIAIVM
53202 rasanlaatkMSECVlg
54989 rnfttaPAICHegkayf
58143 sgncdvvigiinNTVYD
58730 sivAYTMSl
61554 stdliknqCVNFNfn
61598 stffSTFKCYGVSatkl
62872 tagWTFGAgaalqipfa
63309 tecanlllqygsFCTQL
68971 vigiinNTVYDplqpel
72205 VYYPDeifrsdtlyltqd
74173 yicgDSTECanlllqyg
75920 ysvlynstffSTFKCYG
99918 CTFEYisdafsld
100048 gaalqipFAMQMAYRF
100230 ksivAYTMSlgadssiay
100300 MAYRFNGIgvtqnvly
100316 nafnCTFEYisdafsldv
100537 swfiTQRNFfspqii
100711 agclIGAEHvdtsyecdi
129239 liaprGYFKIrsgkssi
532052 gtswfiTQRNFfspq
873061 mmcehiyytcvrTSVDCc
874104 ytcvrTSVDCcmkgaep

IEDB Immune Epitope Database, aa amino acid

Three points need to be stressed.

First, short peptides that are foreign to the host immune system have been experimentally validated not only as positive immunomodulants (i.e., adjuvants) in conjunction to vaccines, but are also evidenced as providing direct protection against lethal viral infections, at least in animal models.6

Second, searching for the 107 human-foreign spike protein pentapeptides in the Immune Epitope Database (IEDB; www.iedb.org)8 yielded a list of n = 66 epitopes (Table 1, Panel b). The IEDB is a publicly available, curated epitope repository. The presence of a peptide sequence in the IEDB indicates that it has a recognized and experimentally proven immunologic relevance. These results provide experimental proof for the immunogenic potential of the non-self peptides identified in the present study through comparative Homo sapiens-coronavirus proteome analysis.

Third, an immune response induced by the spike protein oligopeptides that are absent in the human proteins would exert a neutralizing effect on the coronavirus, in light of the mounting evidence for the surface glycoprotein as a ligand for the human ACE2 in viral entry processes.2

Supplementary information

Table S1 (486.3KB, docx)

Acknowledgements

The author is supported by a “Gerhard Domagk” research grant awarded by the University of Greifswald Medical School.

Competing interests

The author declares no competing interests.

Footnotes

The original online version of this article was revised for Retroperspective open access

Supplementary information

The online version of this article (10.1038/s41423-020-0377-z) contains supplementary material.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Table S1 (486.3KB, docx)

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