Novel Nested Peptide Epitopes Recognized by CD4+ T Cells Induced by HIV-1 Conserved-Region Vaccines

Borthwick, Nicola; Silva-Arrieta, Sandra; Llano, Anuska; Takiguchi, Masafumi; Berthou, Christian; Hanke, Tomáš

doi:10.3390/vaccines8010028

Cited by 8 publications

(10 citation statements)

References 56 publications

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“…In contrast, the selected CTL was linked with the help of Ala-Ala-Tyr (AAY) linkers, the HTL was linked with Gly-Pro-Gly-Pro-Gly (GPGPG) linkers and the LBL was linked with Lys-Lys (KK) linker (Dorosti et al., 2019 ; Nain et al., 2019 ). The AAY linker is a type of cleavage site of proteasomes that was used to influence protein stability, reduce less immunogenicity and enhance epitope presentation (Abdellrazeq et al., 2020 ; Borthwick et al., 2020 ). The GPGPG, known as the glycine–proline linker, prevents the formation of ‘junctional epitopes’ and facilitates the immune processing, where the bi-lysine KK linker helps to preserve their independent immunogenic activities of the vaccine construct.…”

Section: Methodsmentioning

confidence: 99%

“…The S-protein of the virus contains two subunit, S1 and S2; the S1 subunit of the S-protein recognizes the host T-cells while S2 subunit mediates fusion between the viral and host T-cells (Astuti & Ysrafil, 2020 ) and characterizes as a highly antigenic and surface exposure (Shang et al., 2020 ; Wrapp et al., 2020 ). The CD8+ and CD4+ T-cells recognize viral epitopes presented by the major histocompatibility complex class I (MHC I) and class II (MHC II), respectively (Abdellrazeq et al., 2020 ; Borthwick et al., 2020 ). The heterogeneity in T-cells responses to SARS-CoV-2 may, in part, be related to the capacity to recognize the viral antigens in the context of MHC I and MHC II proteins (Astuti & Ysrafil, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Designing a multi-epitope vaccine against SARS-CoV-2: an immunoinformatics approach

Samad¹,

Ahammad

Nain

et al. 2020

Journal of Biomolecular Structure and Dynamics

126

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Ongoing COVID-19 outbreak has raised a drastic challenge to global public health security. Most of the patients with COVID-19 suffer from mild flu-like illnesses such as cold and fever; however, few percentages of the patients progress from severe illness to death, mostly in an immunocompromised individual. The causative agent of COVID-19 is an RNA virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite these debilitating conditions, no medication to stop the disease progression or vaccination is available till now. Therefore, we aimed to formulate a multi-epitope vaccine against SARS-CoV-2 by utilizing an immunoinformatics approach. For this purpose, we used the SARS-CoV-2 spike glycoprotein to determine the immunodominant T-and B-cell epitopes. After rigorous assessment, we designed a vaccine construct using four potential epitopes from each of the three epitope classes such as cytotoxic T-lymphocytes, helper T-lymphocyte, and linear B-lymphocyte epitopes. The designed vaccine was antigenic, immunogenic, and non-allergenic with suitable physicochemical properties and has higher solubility. More importantly, the predicted vaccine structure was similar to the native protein. Further investigations indicated a strong and stable binding interaction between the vaccine and the toll-like receptor (TLR4). Strong binding stability and structural compactness were also evident in molecular dynamics simulation. Furthermore, the computer-generated immune simulation showed that the vaccine could trigger real-lifelike immune responses upon administration into humans. Finally, codon optimization based on Escherichia coli K12 resulted in optimal GC content and higher CAI value followed by incorporating it into the cloning vector pET28þ(a). Overall, these results suggest that the designed peptide vaccine can serve as an excellent prophylactic candidate against SARS-CoV-2.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Designing a multi-epitope vaccine against SARS-CoV-2: an immunoinformatics approach

Samad¹,

Ahammad

Nain

et al. 2020

Journal of Biomolecular Structure and Dynamics

126

View full text Add to dashboard Cite

show abstract

“…Definition of CTL epitopes provides important insights into the mechanisms of host responses to HIV-1 and HIV-1′s adaptation to T-cell surveillance [ 14 , 31 , 74 , 75 , 76 , 77 ]. It also critically informs development of an effective HIV-1 vaccine [ 62 , 63 , 78 , 79 ]. In the course of this work, we characterized a number of CD8 + T-cell responses specific for HIV-1 conserved protein regions induced by the HIVconsv vaccines [ 53 ] in adult HIV-1/2-negative HIV-CORE 004 participants in Nairobi [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

“…These regions contain epitopes typically subdominant in natural HIV-1 infection, but are capable of inducting robust T-cell responses when delivered by a potent vaccination regimen [ 50 , 56 , 57 , 58 , 59 , 60 ]. Such vaccine-elicited responses thus represent a rich source of previously undescribed, potentially important epitopes [ 61 , 62 , 63 ]. In the present work, we characterize CD8 + T-cell responses induced by the first generation of conserved-region vaccines expressing immunogen HIVconsv [ 53 ] in an HIV-1-negative population in the Kangemi district of Nairobi, Kenya [ 60 ], and confirm a number of already-known as well as identify novel conserved CD8 + T-cell epitopes.…”

Section: Introductionmentioning

confidence: 99%

Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya

et al. 2020

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Sub-Saharan Africa carries the biggest burden of the human immunodeficiency virus type 1 (HIV-1)/AIDS epidemic and is in an urgent need of an effective vaccine. CD8+ T cells are an important component of the host immune response to HIV-1 and may need to be harnessed if a vaccine is to be effective. CD8+ T cells recognize human leukocyte antigen (HLA)-associated viral epitopes and the HLA alleles vary significantly among different ethnic groups. It follows that definition of HIV-1-derived peptides recognized by CD8+ T cells in the geographically relevant regions will critically guide vaccine development. Here, we study fine details of CD8+ T-cell responses elicited in HIV-1/2-uninfected individuals in Nairobi, Kenya, who received a candidate vaccine delivering conserved regions of HIV-1 proteins called HIVconsv. Using 10-day cell lines established by in vitro peptide restimulation of cryopreserved PBMC and stably HLA-transfected 721.221/C1R cell lines, we confirm experimentally many already defined epitopes, for a number of epitopes we define the restricting HLA molecule(s) and describe four novel HLA-epitope pairs. We also identify specific dominance patterns, a promiscuous T-cell epitope and a rescue of suboptimal T-cell epitope induction in vivo by its functional variant, which all together inform vaccine design.

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“…Peptides are an important class of biomolecules composed of amino acids and form many important signaling epitopes for a number of biological events . Peptides therefore find a unique place in both drug discovery and drug delivery applications.…”

Section: Introductionmentioning

confidence: 99%

Peptide-Chitosan Engineered Scaffolds for Biomedical Applications

et al. 2021

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Peptides are signaling epitopes that control many vital biological events. Increased specificity, synthetic feasibility with concomitant lack of toxicity, and immunogenicity make this emerging class of biomolecules suitable for different applications including therapeutics, diagnostics, and biomedical engineering. Further, chitosan, a naturally occurring linear polymer composed of D-glucosamine and N-acetyl-D-glucosamine units, possesses anti-microbial, muco-adhesive, and hemostatic properties along with excellent biocompatibility. As a result, chitosan finds application in drug/gene delivery, tissue engineering, and bioimaging. Despite these applications, chitosan demonstrates limited cell adhesion and lacks biosignaling. Therefore, peptide−chitosan hybrids have emerged as a new class of biomaterial with improved biosignaling properties and cell adhesion properties. As a result, recent studies encompass increased application of peptide−chitosan hybrids as composites or conjugates in drug delivery, cell therapy, and tissue engineering and as anti-microbial material. This review discusses the recent investigations involving chitosan−peptide materials and uncovers various aspects of these interesting hybrid materials for biomedical applications.

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Novel Nested Peptide Epitopes Recognized by CD4+ T Cells Induced by HIV-1 Conserved-Region Vaccines

Cited by 8 publications

References 56 publications

Designing a multi-epitope vaccine against SARS-CoV-2: an immunoinformatics approach

Designing a multi-epitope vaccine against SARS-CoV-2: an immunoinformatics approach

Specificity of CD8+ T-Cell Responses Following Vaccination with Conserved Regions of HIV-1 in Nairobi, Kenya

Peptide-Chitosan Engineered Scaffolds for Biomedical Applications

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