Dataset Information

Cross-protection induced by highly conserved human B, CD4⁺, and CD8⁺ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern.

ABSTRACT:

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⁺, 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-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⁺ and CD4⁺ T_EM and T_RM 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.

SUBMITTER: Prakash S

PROVIDER: S-EPMC10839970 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

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.

Prakash Swayam S Dhanushkodi Nisha R NR Zayou Latifa L Ibraim Izabela Coimbra IC Quadiri Afshana A Coulon Pierre Gregoire PG Tifrea Delia F DF Suzer Berfin B Shaik Amin Mohammed AM Chilukuri Amruth A Edwards Robert A RA Singer Mahmoud M Vahed Hawa H Nesburn Anthony B AB Kuppermann Baruch D BD Ulmer Jeffrey B JB Gil Daniel D Jones Trevor M TM BenMohamed Lbachir L

Frontiers in immunology 20240122

<h4>Background</h4>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- ...[more]

PMID: 38318166

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Project description:BackgroundRespiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.MethodsWe focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models.ResultsFor each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage.ConclusionIn conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

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Dataset Information

Cross-protection induced by highly conserved human B, CD4⁺, and CD8⁺ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern.

Background

Methods

Results

Conclusion

Publications

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.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Cross-protection induced by highly conserved human B, CD4+, and CD8+ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern.

Background

Methods

Results

Conclusion

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Cross-protection induced by highly conserved human B, CD4⁺, and CD8⁺ T-cell epitopes-based vaccine against severe infection, disease, and death caused by multiple SARS-CoV-2 variants of concern.