Inovio Pharmaceuticals Inc (INO)

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2/16/22 Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein, Emerging Microbes & Infections,
The mice were injected twice with a two-week interval via the intramuscular route (i.m.) with 25 µg of pVAX-S-WT, made from the wild-type sequence of the full-length spike protein of the SARS-CoV-2 (SARS-CoV-2/WH-09/human/2020/CHN), or with pGX9501 expressing a synthetic, optimized sequence of the SARS-CoV-2 full-length spike glycoprotein15. Electroporation was applied with the Cellectro2000™ device. Serum samples and spleens were collected 14 days after the second immunization.

https://www.tandfonline.com/doi/full/10.1080/22221751.2022.2043727

This work was supported by the Chinese National Natural Science Foundation (81991492 and 82041039) and the National Key R&D Program of the Chinese Ministry of Science & Technology (2018YFC0840402) to B.Wang. We wish to thank Dr. Douglas Lowrie for proofreading this revised manuscript and Dr. Yiwei Zhong at Shanghai Medical College of Fudan University for her technical support.

The SARS-CoV-2 virus was found to mutate rapidly. Accordingly, the development of vaccines protecting people from different virus variants is urgently needed. The neutralizing antibodies induced by vaccines were found to have variable efficacies against the different SARS-CoV-2 variants, and efficacies declined over time, whereas the protection represented by CD8+ T cell immunity remained unchanged24. Peptide 2 is a highly conserved epitope among all variants and well-presented by MHC-1 of all HLA alleles across the globe. Thus, the conserved Peptide 2 should be suitable for evaluating COVID-19 vaccines for T cell response, particularly for the CD8 T cell-mediated functions. It is also possible to include such an epitope in new COVID-19 vaccines to induce a robust cellular response against all variants of SARS-CoV-2. A recent study confirmed that Peptide 2 probably has a strong cell-mediated immunological function in man; a 9-mer (YLQPRTFLL) peptide overlapped by Peptide 2 could induce a high level of IFN-? expression from PBMCs of patients who had recovered from COVID-19 and carried the HLA-A*02:01 allele29. The 9-mer peptide only showed a relatively good MHC-I binding ability in H-2Ld allele (STable 1), and it stimulated a weaker IFN-? T cell response than Peptide 2 in mice (Sfigure 2). In conclusion, our study utilized web-based tools to predict human MHC-I epitopes and found several sequences falling into the category. Among these, Peptide 2 (YYVGYLQPRTFLLKY) was not given the most decisive total TAP score in the prediction, but overall it simulated a more robust antigen-specific IFN-?-expressing CD8+ T response compared to the other predicted epitopic sequences. This epitope sequence is located at the end of NTD of the spike protein and is highly conservative among the currently known SARS-CoV-2 variants and recognizable with the diverse HLA alleles prominent in most world populations. This critical MHC-I epitope can be used to assess CMI induced by COVID-19 vaccines and maybe strategically incorporated into vaccine designs to enhance the prospect of viral elimination by vaccination.