Novel approaches in polyepitope T-cell vaccine development against HIV-1

ABSTRACTCytotoxic T lymphocytes (CTLs) with strong abilities to suppress HIV-1 replication and recognize circulating HIV-1 could be key for both HIV-1 cure and prophylaxis. We recently designed conserved mosaic T-cell vaccine immunogens (tHIVconsvX) composed of 6 Gag and Pol regions. Since the tHIVconsvX vaccine targets conserved regions common to most global HIV-1 variants and employs a bivalent mosaic design, it is expected that it could be universal if the vaccine works. Although we recently demonstrated that CTLs specific for 5 Gag epitopes in the vaccine immunogens had strong ability to suppress HIV-1 replicationin vitroandin vivo, it remains unknown whether the Pol region-specific CTLs are equally efficient. In this study, we investigated CTLs specific for Pol epitopes in the immunogens in treatment-naive Japanese patients infected with HIV-1 clade B. Overall, we mapped 20 reported and 5 novel Pol conserved epitopes in tHIVconsvX. Responses to 6 Pol epitopes were significantly associated with good clinical outcome, suggesting that CTLs specific for these 6 Pol epitopes had a strong ability to suppress HIV-1 replication in HIV-1-infected individuals.In vitroT-cell analyses further confirmed that the Pol-specific CTLs could effectively suppress HIV-1 replication. The present study thus demonstrated that the Pol regions of the vaccine contained protective epitopes. T-cell responses to the previous 5 Gag and present 6 Pol protective epitopes together also showed a strong correlation with better clinical outcome. These findings support the testing of the conserved mosaic vaccine in HIV-1 cure and prevention in humans.IMPORTANCEIt is likely necessary for an effective AIDS vaccine to elicit CD8+T cells with the ability to recognize circulating HIV-1 and suppress its replication. We recently developed novel bivalent mosaic T-cell vaccine immunogens composed of conserved regions of the Gag and Pol proteins matched to at least 80% globally circulating HIV-1 isolates. Nevertheless, it remains to be proven if vaccination with these immunogens can elicit T cells with the ability to suppress HIV-1 replication. It is well known that Gag-specific T cells can suppress HIV-1 replication more effectively than T cells specific for epitopes in other proteins. We recently identified 5 protective Gag epitopes in the vaccine immunogens. In this study, we identified T cells specific for 6 Pol epitopes present in the immunogens with strong abilities to suppress HIV-1in vivoandin vitro. This study further encourages clinical testing of the conserved mosaic T-cell vaccine in HIV-1 prevention and cure.

Download Full-text

Immune Responses to Dengue and Zika Viruses—Guidance for T Cell Vaccine Development

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph15020385 ◽

2018 ◽

Vol 15 (2) ◽

pp. 385 ◽

Cited By ~ 7

Author(s):

Claude Roth ◽

Félix Delgado ◽

Etienne Simon-Lorière ◽

Anavaj Sakuntabhai

Keyword(s):

T Cell ◽

Immune Responses ◽

Vaccine Development ◽

Cell Vaccine ◽

T Cell Vaccine

Download Full-text

Inferring MHC interacting SARS-CoV-2 epitopes recognized by TCRs towards designing T cell-based vaccines

10.1101/2020.09.12.294413 ◽

2020 ◽

Author(s):

Amir Hossein Mohseni ◽

Sedigheh Taghinezhad-S ◽

Bing Su ◽

Feng Wang

Keyword(s):

T Cell ◽

Vaccine Development ◽

Cell Receptor ◽

Health Concern ◽

Cell Vaccine ◽

Physiochemical Properties ◽

Peptide Epitopes ◽

Mhc Molecules ◽

T Cell Vaccine ◽

T Cell Immune Responses

AbstractThe coronavirus disease 2019 (COVID-19) is triggered by severe acute respiratory syndrome mediated by coronavirus 2 (SARS-CoV-2) infection and was declared by WHO as a major international public health concern. While worldwide efforts are being advanced towards vaccine development, the structural modeling of TCR-pMHC (T Cell Receptor-peptide-bound Major Histocompatibility Complex) regarding SARS-CoV-2 epitopes and the design of effective T cell vaccine based on these antigens are still unresolved. Here, we present both pMHC and TCR-pMHC interfaces to infer peptide epitopes of the SARS-CoV-2 proteins. Accordingly, significant TCR-pMHC templates (Z-value cutoff > 4) along with interatomic interactions within the SARS-CoV-2-derived hit peptides were clarified. Also, we applied the structural analysis of the hit peptides from different coronaviruses to highlight a feature of evolution in SARS-CoV-2, SARS-CoV, bat-CoV, and MERS-CoV. Peptide-protein flexible docking between each of the hit peptides and their corresponding MHC molecules were performed, and a multi-hit peptides vaccine against the S and N glycoprotein of SARS-CoV-2 was designed. Filtering pipelines including antigenicity, and also physiochemical properties of designed vaccine were then evaluated by different immunoinformatics tools. Finally, vaccine-structure modeling and immune simulation of the desired vaccine were performed aiming to create robust T cell immune responses. We anticipate that our design based on the T cell antigen epitopes and the frame of the immunoinformatics analysis could serve as valuable supports for the development of COVID-19 vaccine.

Download Full-text