tetano
Editor, Senior Moderator
Front Immunol
. 2024 Jan 22:15:1328905.
doi: 10.3389/fimmu.2024.1328905. eCollection 2024. Cross-protection induced by highly conserved human B, CD4[SUP]+[/SUP], and CD8[SUP]+[/SUP] T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern
Swayam Prakash[SUP] 1 [/SUP], Nisha R Dhanushkodi[SUP] 1 [/SUP], Latifa Zayou[SUP] #[/SUP][SUP] 1 [/SUP], Izabela Coimbra Ibraim[SUP] #[/SUP][SUP] 2 [/SUP], Afshana Quadiri[SUP] 1 [/SUP], Pierre Gregoire Coulon[SUP] 1 [/SUP], Delia F Tifrea[SUP] 3 [/SUP], Berfin Suzer[SUP] 1 [/SUP], Amin Mohammed Shaik[SUP] 1 [/SUP], Amruth Chilukuri[SUP] 1 [/SUP], Robert A Edwards[SUP] 3 [/SUP], Mahmoud Singer[SUP] 1 [/SUP], Hawa Vahed[SUP] 4 [/SUP], Anthony B Nesburn[SUP] 1 [/SUP], Baruch D Kuppermann[SUP] 1 [/SUP], Jeffrey B Ulmer[SUP] 4 [/SUP], Daniel Gil[SUP] 4 [/SUP], Trevor M Jones[SUP] 4 [/SUP], Lbachir BenMohamed[SUP] 1 4 5 6 [/SUP]
Affiliations
Background: The coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 remains a serious cause of morbidity and mortality worldwide, with the mortality rate still substantially surpassing even that recorded for influenza viruses. The continued emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, has prolonged the COVID-19 pandemic and underscores the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs.
Methods: We designed a multi-epitope-based coronavirus vaccine that incorporated B, CD4[SUP]+[/SUP], and CD8[SUP]+[/SUP] T- cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-variant SARS-CoV-2 vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model.
Results: The pan-variant SARS-CoV-2 vaccine (i) is safe , (ii) induces high frequencies of lung-resident functional CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] T[SUB]EM[/SUB] and T[SUB]RM[/SUB] cells , and (iii) provides robust protection against morbidity and virus replication. COVID-19-related lung pathology and death were 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).
Conclusion: A multi-epitope pan-variant SARS-CoV-2 vaccine bearing conserved human B- and T- cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that facilitated virus clearance, and reduced morbidity, COVID-19-related lung pathology, and death caused by multiple SARS-CoV-2 VOCs.
Keywords: COVID-19; SARS-CoV-2; SL-CoVs; T cells; antibodies; epitopes; immunity; vaccine.
. 2024 Jan 22:15:1328905.
doi: 10.3389/fimmu.2024.1328905. eCollection 2024. Cross-protection induced by highly conserved human B, CD4[SUP]+[/SUP], and CD8[SUP]+[/SUP] T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern
Swayam Prakash[SUP] 1 [/SUP], Nisha R Dhanushkodi[SUP] 1 [/SUP], Latifa Zayou[SUP] #[/SUP][SUP] 1 [/SUP], Izabela Coimbra Ibraim[SUP] #[/SUP][SUP] 2 [/SUP], Afshana Quadiri[SUP] 1 [/SUP], Pierre Gregoire Coulon[SUP] 1 [/SUP], Delia F Tifrea[SUP] 3 [/SUP], Berfin Suzer[SUP] 1 [/SUP], Amin Mohammed Shaik[SUP] 1 [/SUP], Amruth Chilukuri[SUP] 1 [/SUP], Robert A Edwards[SUP] 3 [/SUP], Mahmoud Singer[SUP] 1 [/SUP], Hawa Vahed[SUP] 4 [/SUP], Anthony B Nesburn[SUP] 1 [/SUP], Baruch D Kuppermann[SUP] 1 [/SUP], Jeffrey B Ulmer[SUP] 4 [/SUP], Daniel Gil[SUP] 4 [/SUP], Trevor M Jones[SUP] 4 [/SUP], Lbachir BenMohamed[SUP] 1 4 5 6 [/SUP]
Affiliations
- PMID: 38318166
- PMCID: PMC10839970
- DOI: 10.3389/fimmu.2024.1328905
Background: The coronavirus disease 2019 (COVID-19) pandemic has created one of the largest global health crises in almost a century. Although the current rate of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has decreased significantly, the long-term outlook of COVID-19 remains a serious cause of morbidity and mortality worldwide, with the mortality rate still substantially surpassing even that recorded for influenza viruses. The continued emergence of SARS-CoV-2 variants of concern (VOCs), including multiple heavily mutated Omicron sub-variants, has prolonged the COVID-19 pandemic and underscores the urgent need for a next-generation vaccine that will protect from multiple SARS-CoV-2 VOCs.
Methods: We designed a multi-epitope-based coronavirus vaccine that incorporated B, CD4[SUP]+[/SUP], and CD8[SUP]+[/SUP] T- cell epitopes conserved among all known SARS-CoV-2 VOCs and selectively recognized by CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] T-cells from asymptomatic COVID-19 patients irrespective of VOC infection. The safety, immunogenicity, and cross-protective immunity of this pan-variant SARS-CoV-2 vaccine were studied against six VOCs using an innovative triple transgenic h-ACE-2-HLA-A2/DR mouse model.
Results: The pan-variant SARS-CoV-2 vaccine (i) is safe , (ii) induces high frequencies of lung-resident functional CD8[SUP]+[/SUP] and CD4[SUP]+[/SUP] T[SUB]EM[/SUB] and T[SUB]RM[/SUB] cells , and (iii) provides robust protection against morbidity and virus replication. COVID-19-related lung pathology and death were 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).
Conclusion: A multi-epitope pan-variant SARS-CoV-2 vaccine bearing conserved human B- and T- cell epitopes from structural and non-structural SARS-CoV-2 antigens induced cross-protective immunity that facilitated virus clearance, and reduced morbidity, COVID-19-related lung pathology, and death caused by multiple SARS-CoV-2 VOCs.
Keywords: COVID-19; SARS-CoV-2; SL-CoVs; T cells; antibodies; epitopes; immunity; vaccine.