An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines

Lucchese, Guglielmo; Jahantigh, Hamid Reza; Benedictis, Leonarda De; Lovreglio, Piero; Stufano, Angela

doi:10.3390/v13081461

Cited by 7 publications

(3 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our vaccine design centered on the envelope glycoprotein gp62, a key outer membrane protein containing numerous epitope binding sites crucial for the infectious process and immune response of HTLV [70,71]. Epitope mapping was executed to identify T cell and B cell epitopes, both essential for provoking the host's immune response to viral infection [72,73].…”

Section: Discussionmentioning

confidence: 99%

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

Moin,

Rani,

Ullah

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

Human T-lymphotropic virus (HTLV), a group of retroviruses belonging to the oncovirus family, has long been associated with various inflammatory and immunosuppressive disorders. At present, there is no approved vaccine capable of effectively combating all the highly pathogenic strains of HTLV that makes this group of viruses a potential threat to human health. To combat the devastating impact of any potential future outbreak caused by this virus group, our study employed a reverse vaccinology approach to design a novel polyvalent vaccine targeting the highly virulent subtypes of HTLV. Moreover, we comprehensively analyzed the molecular interactions between the designed vaccine and corresponding Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine’s stability, antigenicity, and immunogenicity. Initially, two vaccine constructs were formulated, and among them, vaccine construct-2 exhibited superior solubility and structural stability. Molecular docking analyses also revealed strong binding affinity between the vaccine construct-2 and both targeted TLR2 and TLR4. Molecular dynamics simulations demonstrated enhanced stability, compactness, and consistent hydrogen bonding within TLR-vaccine complexes, suggesting a strong binding affinity. The stability of the complexes was further corroborated by contact, free energy, structure, and MM-PBSA analyses. Consequently, our research proposes a vaccine targeting multiple HTLV subtypes, offering valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to developing effective preventive and treatment approaches against HTLV-related diseases and preventing possible outbreaks. However, future research should focus on in-depth validation through experimental studies to confirm the interactions identified in silico and to evaluate the vaccine’s efficacy in relevant animal models and, eventually, in clinical trials.

show abstract

Section: Discussionmentioning

confidence: 99%

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

Moin,

Rani,

Ullah

et al. 2023

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…The vaccine was designed by targeting the envelope glycoprotein gp62, an outer membrane protein having a greater number of epitope binding site that plays a significant role in the infectious process and immune response of HTLV (67,68). The selected proteins were predicted to be antigenic and having desirable biophysical properties that are expected in vaccine development.…”

Section: Discussionmentioning

confidence: 99%

Accelerating Cancer Vaccine Development for Human T-Lymphotropic Virus (HTLV) Using a High-Throughput Molecular Dynamics Approach

Moin,

Rani,

Ullah

et al. 2023

Preprint

View full text Add to dashboard Cite

Human T-lymphotropic virus (HTLV), a retrovirus belonging to the oncovirus family, has long been linked to be associated with various inflammatory and immunosuppressive disorders. To combat the devastating impact of this virus, our study employed a reverse vaccinology approach to design a multi-epitope-based vaccine targeting the highly virulent subtypes of HTLV. We conducted a comprehensive analysis of the molecular interactions between the vaccine and Toll-like receptors (TLRs), providing valuable insights for future research on preventing and managing HTLV-related diseases and any possible outbreaks. The vaccine was designed by focusing on the envelope glycoprotein gp62, a crucial protein involved in the infectious process and immune mechanisms of HTLV inside the human body. Epitope mapping identified T cell and B cell epitopes with low binding energies, ensuring their immunogenicity and safety. Linkers and adjuvants were incorporated to enhance the vaccine's stability, antigenicity, and immunogenicity. Two vaccine constructs were developed, both exhibiting high antigenicity and conferring safety. Vaccine construct 2 demonstrated expected solubility and structural stability after disulfide engineering. Molecular docking analyses revealed strong binding affinity between the vaccine construct 2 and both TLR2 and TLR4. Molecular dynamics simulations indicated that the TLR2-vaccine complex displayed enhanced stability, compactness, and consistent hydrogen bond formation, suggesting a favorable affinity. Contact analysis, Gibbs free energy landscapes, and DCC analysis further supported the stability of the TLR2-vaccine complex, while DSSP analysis confirmed stable secondary structures. MM-PBSA analysis revealed a more favorable binding affinity of the TLR4-vaccine complex, primarily due to lower electrostatic energy. In conclusion, our study successfully designed a multi-epitope-based vaccine targeting HTLV subtypes and provided valuable insights into the molecular interactions between the vaccine and TLRs. These findings should contribute to the development of effective preventive and treatment approaches against HTLV-related diseases.

show abstract

“…Based on the knowledge advances in the HTLV-host interaction and in the biotechnology recent systematic reviews and reports showed a plethora of approaches for HTLV-1 vaccine candidates: viral like particles vectors and viral vectors (Vaccinia virus, Adenovirus and Sendai virus), dendritic cell and peptide-based vaccines, recombinant single proteins or multiepitope proteins expressed in different systems including molecules encapsulated using nanotechnology [ 9 – 13 ]. Of great interest 15 peptide stretches (from Gag and Gag-Pro-Pol polyproteins, Tax-1 and gp62) were presented from an epitope platform for HTLV-1 vaccine development of uniquely viral non-human pentapeptides to avoid cross-reaction, generating safe immunization based on peptides and mRNA [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

Daian e Silva,

Cox,

Rocha

et al. 2023

Virol J

View full text Add to dashboard Cite

Background Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load. Methods We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4+ and T CD8+) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen. Results T CD4+ and T CD8+ lymphocytes cells stimulated by HBZ-peptides (HBZ42–50 and HBZ157–176) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8+ cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44+High/CD62L−Low), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8+ T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA. Conclusions Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.

show abstract

An Epitope Platform for Safe and Effective HTLV-1-Immunization: Potential Applications for mRNA and Peptide-Based Vaccines

Cited by 7 publications

References 67 publications

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

An immunoinformatics and extended molecular dynamics approach for designing a polyvalent vaccine against multiple strains of Human T-lymphotropic virus (HTLV)

Accelerating Cancer Vaccine Development for Human T-Lymphotropic Virus (HTLV) Using a High-Throughput Molecular Dynamics Approach

Preclinical assessment of an anti-HTLV-1 heterologous DNA/MVA vaccine protocol expressing a multiepitope HBZ protein

Contact Info

Product

Resources

About