Immune responses of seven different “promiscuous” T-cell epitopes on chimeric peptide vaccine design

Peptides ◽  
1994 ◽  
pp. 732-733 ◽  
Author(s):  
A. M. DiGeorge ◽  
B. Wang ◽  
S. F. Kobs-Conrad ◽  
P. T. P. Kaumaya
Author(s):  
Arpita Singha Roy ◽  
Mahafujul Islam Quadery Tonmoy ◽  
Atqiya Fariha ◽  
Ithmam Hami ◽  
Ibrahim Khalil Afif ◽  
...  

AbstractSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the novel coronavirus responsible for the ongoing pandemic of coronavirus disease (COVID-19). No sustainable treatment option is available so far to tackle such a public health threat. Therefore, designing a suitable vaccine to overcome this hurdle asks for immediate attention. In this study, we targeted for a design of multi-epitope based vaccine using immunoinformatics tools. We considered the structural proteins S, E and, M of SARS-CoV-2, since they facilitate the infection of the virus into host cell and using different bioinformatics tools and servers, we predicted multiple B-cell and T-cell epitopes having potential for the required vaccine design. Phylogenetic analysis provided insight on ancestral molecular changes and molecular evolutionary relationship of S, E, and M proteins. Based on the antigenicity and surface accessibility of these proteins, eight epitopes were selected by various B cell and T cell epitope prediction tools. Molecular docking was executed to interpret the binding interactions of these epitopes and three potential epitopes WTAGAAAYY, YVYSRVKNL, and GTITVEELK were selected for their noticeable higher binding affinity scores −9.1, −7.4, and −7.0 kcal/mol, respectively. Targeted epitopes had 91.09% population coverage worldwide. In summary, we identified three epitopes having the most significant properties of designing the peptide-based vaccine against SARS-CoV-2.


2021 ◽  
Author(s):  
Alison Tarke ◽  
John Sidney ◽  
Nils Methot ◽  
Yun Zhang ◽  
Jennifer M Dan ◽  
...  

The emergence of SARS-CoV-2 variants highlighted the need to better understand adaptive immune responses to this virus. It is important to address whether also CD4+ and CD8+ T cell responses are affected, because of the role they play in disease resolution and modulation of COVID-19 disease severity. Here we performed a comprehensive analysis of SARS-CoV-2-specific CD4+ and CD8+ T cell responses from COVID-19 convalescent subjects recognizing the ancestral strain, compared to variant lineages B.1.1.7, B.1.351, P.1, and CAL.20C as well as recipients of the Moderna (mRNA-1273) or Pfizer/BioNTech (BNT162b2) COVID-19 vaccines. Similarly, we demonstrate that the sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the variants analyzed. Overall, the results demonstrate that CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants.


Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 350 ◽  
Author(s):  
Maria Agallou ◽  
Maritsa Margaroni ◽  
Stathis D. Kotsakis ◽  
Evdokia Karagouni

Leishmaniases are complex vector-borne diseases caused by intracellular parasites of the genus Leishmania. The visceral form of the disease affects both humans and canids in tropical, subtropical, and Mediterranean regions. One health approach has suggested that controlling zoonotic visceral leishmaniasis (ZVL) could have an impact on the reduction of the human incidence of visceral leishmaniasis (VL). Despite the fact that a preventive vaccination could help with leishmaniasis elimination, effective vaccines that are able to elicit protective immune responses are currently lacking. In the present study, we designed a chimeric multi-epitope protein composed of multiple CD8+ and CD4+ T cell epitopes which were obtained from six highly immunogenic proteins previously identified by an immunoproteomics approach, and the N-termini of the heparin-binding hemagglutinin (HBHA) of Mycobacterium tuberculosis served as an adjuvant. A preclinical evaluation of the candidate vaccine in BALB/c mice showed that when it was given along with the adjuvant Addavax it was able to induce strong immune responses. Cellular responses were dominated by the presence of central and effector multifunctional CD4+ and CD8+ T memory cells. Importantly, the vaccination reduced the parasite burden in both short-term and long-term vaccinated mice challenged with Leishmania infantum. Protection was characterized by the continuing presence of IFN-γ+TNFα+-producing CD8+ and CD4+ T cells and increased NO levels. The depletion of CD8+ T cells in short-term vaccinated mice conferred a significant loss of protection in both target organs of the parasite, indicating a significant involvement of this population in the protection against L. infantum challenge. Thus, the overall data could be considered to be a proof-of-concept that the design of efficacious T cell vaccines with the help of reverse vaccinology approaches is possible.


Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 290 ◽  
Author(s):  
Sumit Mukherjee ◽  
Dmitry Tworowski ◽  
Rajesh Detroja ◽  
Sunanda Biswas Mukherjee ◽  
Milana Frenkel-Morgenstern

A new coronavirus infection, COVID-19, has recently emerged, and has caused a global pandemic along with an international public health emergency. Currently, no licensed vaccines are available for COVID-19. The identification of immunodominant epitopes for both B- and T-cells that induce protective responses in the host is crucial for effective vaccine design. Computational prediction of potential epitopes might significantly reduce the time required to screen peptide libraries as part of emergent vaccine design. In our present study, we used an extensive immunoinformatics-based approach to predict conserved immunodominant epitopes from the proteome of SARS-CoV-2. Regions from SARS-CoV-2 protein sequences were defined as immunodominant, based on the following three criteria regarding B- and T-cell epitopes: (i) they were both mapped, (ii) they predicted protective antigens, and (iii) they were completely identical to experimentally validated epitopes of SARS-CoV. Further, structural and molecular docking analyses were performed in order to understand the binding interactions of the identified immunodominant epitopes with human major histocompatibility complexes (MHC). Our study provides a set of potential immunodominant epitopes that could enable the generation of both antibody- and cell-mediated immunity. This could contribute to developing peptide vaccine-based adaptive immunotherapy against SARS-CoV-2 infections and prevent future pandemic outbreaks.


Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 424 ◽  
Author(s):  
Beatriz Perdiguero ◽  
Suresh C. Raman ◽  
Cristina Sánchez-Corzo ◽  
Carlos Oscar S. Sorzano ◽  
José Ramón Valverde ◽  
...  

An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the best solution to provide a sustainable control and/or eradication of the virus. We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and therapeutic clinical trials, but was unable to prevent viral rebound after antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we described the design and immune responses elicited in mice by a new T cell multi-epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous or heterologous prime/boost regimens in combination with MVA-B. The TMEP-B protein contained conserved regions from Gag, Pol, and Nef proteins including multiple CD4 and CD8 T cell epitopes functionally associated with HIV control. Heterologous DNA-TMEP/MVA-B regimen induced higher HIV-1-specific CD8 T cell responses with broader epitope recognition and higher polyfunctional profile than the homologous DNA-TMEP/DNA-TMEP or the heterologous DNA-GPN/MVA-B combinations. Moreover, higher HIV-1-specific CD4 and Tfh immune responses were also detected using this regimen. After MVA-B boost, the magnitude of the anti-VACV CD8 T cell response was significantly compromised in DNA-TMEP-primed animals. Our results revealed the immunological potential of DNA-TMEP prime/MVA-B boost regimen and supported the application of these combined vectors in HIV-1 prevention and/or therapy.


1989 ◽  
Vol 54 (0) ◽  
pp. 497-504 ◽  
Author(s):  
M.T. Scherer ◽  
B.M.C. Chan ◽  
F. Ria ◽  
J.A. Smith ◽  
D.L. Perkins ◽  
...  

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