Cross-Protection Induced by Highly Conserved Human B, CD4+, and CD8+ T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern

Prakash, S. F.; Dhanushkodi, N. R.; Zayou, L.; Ibraim, I. C.; Quadiri, A.; Coulon, P. G.; Tifrea, D. F.; Suzler, B.; Amin, M.; Chilukuri, A.; Edwards, R. A.; Vahed, H.; Nesburn, A. B.; Kuppermann, B. D.; Ulmer, J. B.; Gil, D.; Jones, T. M.; BenMohamed, L.

doi:10.1101/2023.05.24.541850

bioRxiv · 10.1101/2023.05.24.541850

Cross-Protection Induced by Highly Conserved Human B, CD4+, and CD8+ T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern

Prakash, S. F.·Dhanushkodi, N. R.·Zayou, L.·Ibraim, I. C.·Quadiri, A.·Coulon, P. G.·Tifrea, D. F.·Suzler, B.·Amin, M.·Chilukuri, A.·Edwards, R. A.·Vahed, H.·Nesburn, A. B.·Kuppermann, B. D.·Ulmer, J. B.·Gil, D.·Jones, T. M.·BenMohamed, L.

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Abstract

BackgroundThe Coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of SARS-CoV-2 infections has decreased significantly; the long-term outlook of COVID-19 remains a serious cause of high death worldwide; with the mortality rate still surpassing even the worst mortality rates recorded for the influenza viruses. The continuous emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, have prolonged the COVID-19 pandemic and outlines the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs. MethodsIn the present study, we designed a multi-epitope-based Coronavirus vaccine that incorporated B, CD4+, and CD8+ T cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8+ and CD4+ T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-Coronavirus vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model. ResultsThe Pan-Coronavirus vaccine: (i) is safe; (ii) induces high frequencies of lung-resident functional CD8+ and CD4+ TEM and TRM cells; and (iii) provides robust protection against virus replication and COVID-19-related lung pathology and death caused by six SARS-CoV-2 VOCs: Alpha (B.1.1.7), Beta (B.1.351), Gamma or P1 (B.1.1.28.1), Delta (lineage B.1.617.2) and Omicron (B.1.1.529). Conclusions: A multi-epitope pan-Coronavirus vaccine bearing conserved human B and T cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that cleared the virus, and reduced COVID-19-related lung pathology and death caused by multiple SARS-CoV-2 VOCs.

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Prakash, S. F., Dhanushkodi, N. R., Zayou, L., Ibraim, I. C., Quadiri, A., Coulon, P. G., Tifrea, D. F., Suzler, B., Amin, M., Chilukuri, A., Edwards, R. A., Vahed, H., Nesburn, A. B., Kuppermann, B. D., Ulmer, J. B., Gil, D., Jones, T. M., BenMohamed, L.. 2023-05-24. Cross-Protection Induced by Highly Conserved Human B, CD4+, and CD8+ T Cell Epitopes-Based Coronavirus Vaccine Against Severe Infection, Disease, and Death Caused by Multiple SARS-CoV-2 Variants of Concern. https://doi.org/10.1101/2023.05.24.541850

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