scholarly journals Peptide-Based Subunit Vaccine Design of T- and B-Cells Multi-Epitopes against Zika Virus Using Immunoinformatics Approaches

2019 ◽  
Vol 7 (8) ◽  
pp. 226 ◽  
Author(s):  
Vivitri Dewi Prasasty ◽  
Karel Grazzolie ◽  
Rosmalena Rosmalena ◽  
Fatmawaty Yazid ◽  
Fransiskus Xaverius Ivan ◽  
...  

The Zika virus disease, also known as Zika fever is an arboviral disease that became epidemic in the Pacific Islands and had spread to 18 territories of the Americas in 2016. Zika virus disease has been linked to several health problems such as microcephaly and the Guillain–Barré syndrome, but to date, there has been no vaccine available for Zika. Problems related to the development of a vaccine include the vaccination target, which covers pregnant women and children, and the antibody dependent enhancement (ADE), which can be caused by non-neutralizing antibodies. The peptide vaccine was chosen as a focus of this study as a safer platform to develop the Zika vaccine. In this study, a collection of Zika proteomes was used to find the best candidates for T- and B-cell epitopes using the immunoinformatics approach. The most promising T-cell epitopes were mapped using the selected human leukocyte antigen (HLA) alleles, and further molecular docking and dynamics studies showed a good peptide-HLA interaction for the best major histocompatibility complex-II (MHC-II) epitope. The most promising B-cell epitopes include four linear peptides predicted to be cross-reactive with T-cells, and conformational epitopes from two proteins accessible by antibodies in their native biological assembly. It is believed that the use of immunoinformatics methods is a promising strategy against the Zika viral infection in designing an efficacious multiepitope vaccine.

Author(s):  
Jesvin Bency B. ◽  
Mary Helen P. A.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative viral strain for the contagious pandemic respiratory illness in humans which is a public health emergency of international concern. There is a desperate need for vaccines and antiviral strategies to combat the rapid spread of SARS-CoV-2 infection.Methods: The present study based on computational methods has identified novel conserved cytotoxic T-lymphocyte epitopes as well as linear and discontinuous B-cell epitopes on the SARS-CoV-2 spike (S) protein. The predicted MHC class I and class II binding peptides were further checked for their antigenic scores, allergenicity, toxicity, digesting enzymes and mutation.Results: A total of fourteen linear B-cell epitopes where GQSKRVDFC displayed the highest antigenicity-score and sixteen highly antigenic 100% conserved T-cell epitopes including the most potential vaccine candidates MHC class-I peptide KIADYNYKL and MHC class-II peptide VVFLHVTYV were identified. Furthermore, the potential peptide QGFSALEPL with high antigenicity score attached to larger number of human leukocyte antigen alleles. Docking analyses of the allele HLA-B*5201 predicted to be immunogenic to several of the selected epitopes revealed that the peptides engaged in strong binding with the HLA-B*5201 allele.Conclusions: Collectively, this research provides novel candidates for epitope-based peptide vaccine design against SARS-CoV-2 infection.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Muhammad Tahir ul Qamar ◽  
Saman Saleem ◽  
Usman Ali Ashfaq ◽  
Amna Bari ◽  
Farooq Anwar ◽  
...  

Abstract Background Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. Methods The present study used immuno-informatics and computational approaches to identify conserved B- and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. Results Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. Conclusion The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.


2018 ◽  
Vol 24 (11) ◽  
pp. 1157-1173 ◽  
Author(s):  
Kavita Reginald ◽  
Yanqi Chan ◽  
Magdalena Plebanski ◽  
Chit Laa Poh

Dengue is one of the most important arboviral infections worldwide, infecting up to 390 million people and causing 25,000 deaths annually. Although a licensed dengue vaccine is available, it is not efficacious against dengue serotypes that infect people living in South East Asia, where dengue is an endemic disease. Hence, there is an urgent need to develop an efficient dengue vaccine for this region. Data from different clinical trials indicate that a successful dengue vaccine must elicit both neutralizing antibodies and cell mediated immunity. This can be achieved by designing a multi-epitope peptide vaccine comprising B, CD8+ and CD4+ T cell epitopes. As recognition of T cell epitopes are restricted by human leukocyte antigens (HLA), T cell epitopes which are able to recognize several major HLAs will be preferentially included in the vaccine design. While peptide vaccines are safe, biocompatible and cost-effective, it is poorly immunogenic. Strategies to improve its immunogenicity by the use of long peptides, adjuvants and nanoparticle delivery mechanisms are discussed.


2020 ◽  
Author(s):  
Yuwei Li ◽  
Mi Mao ◽  
Liteng Yang ◽  
Xizhuo Sun ◽  
Nanshan Zhong ◽  
...  

Abstract The newly identified 2019 novel coronavirus (2019-nCoV) has caused more than 81,400 laboratory-confirmed human infections, including 3261 deaths, posing a serious threat to human health. Currently, however, there is no specific antiviral treatment or vaccine. To identify immunodominant peptides for designing global peptide vaccine for combating the infections caused by 2019-nCoV, the structure and immunogenicity of 2019-nCoV structural protein were analyzed by bioinformatics tools. 33 B-cell epitopes and 39 T-cell epitopes were determined in four structural proteins via different immunoinformatic tools in which include spike protein (22 B-cell epitopes, 25 T-cell epitopes ), nucleocapsid protein (7 B-cell epitopes, 6 T-cell epitopes), membrane protein (2 B-cell epitopes, 7 T-cell epitopes), and envelope protein (2 B-cell epitopes, 1T-cell epitopes), respectively. The proportion of epitope residues in primary sequence was used to determine the antigenicity and immunogenicity of proteins. The envelope protein has the largest antigenicity in which residue coverage of B-cell epitopes is 24%. The membrane protein possesses the largest immunogenicity in which residue coverage of T-cell epitopes is 55.86%. The reason that immune storm was caused by 2019-nCoV maybe that the membrane and envelope protein expressed plentifully in cell infected. Further, studies involving experimental validation of these predicted epitopes is warranted to ensure the potential of B-cells and T-cells stimulation for their effective use as vaccine candidates. These findings provide the basis for starting further studies on the pathogenesis, and optimizing the design of diagnostic, antiviral and vaccination strategies for this emerging infection.


Author(s):  
Niti Yashvardhini ◽  
Amit Kumar ◽  
Deepak Kumar Jha

SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is a newly emerged beta coronavirus and etiolating agent of COVID-19. Considering the unprecedented increasing number of COVID-19 cases, the World Health Organization declared a public health emergency internationally on 11th March 2020. However, existing drugs are insufficient in dealing with this contagious virus infection; therefore, a vaccine is exigent to curb this pandemic disease. In the present study, B- and T-cell immune epitopes were identified for RdRp (RNA-dependent RNA polymerase) protein using immunoinformatic techniques, which is proved to be a rapid and efficient method to explore the candidate peptide vaccine. Subsequently, antigenicity and interactions with HLA (human leukocyte antigen) alleles were estimated. Further, physicochemical properties, allergenicity, toxicity, and stability of RdRp protein were evaluated to demonstrate the specificity of the epitope candidates. Interestingly, we identified a total of 36 B-cell and 16 T-cell epitopes using epitopes predictive tools. Among the predicted epitopes, 26 B-cell and 9 T-cell epitopes showed non-allergenic, non-toxic, and highly antigenic properties. Altogether, our study revealed that RdRp of SARS-CoV-2 (an epitope-based peptide fragment) can be a potentially good candidate for the development of a vaccine against SARS-CoV-2.


Author(s):  
Ye Feng ◽  
Min Qiu ◽  
Liang Liu ◽  
Shengmei Zou ◽  
Yun Li ◽  
...  

AbstractA new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-γ-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-γ-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides.ImportanceSo far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.


Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 83 ◽  
Author(s):  
Andrey P. Rudometov ◽  
Anton N. Chikaev ◽  
Nadezhda B. Rudometova ◽  
Denis V. Antonets ◽  
Alexander A. Lomzov ◽  
...  

The construction of artificial proteins using conservative B-cell and T-cell epitopes is believed to be a promising approach for a vaccine design against diverse viral infections. This article describes the development of an artificial HIV-1 immunogen using a polyepitope immunogen design strategy. We developed a recombinant protein, referred to as nTBI, that contains epitopes recognized by broadly neutralizing HIV-1 antibodies (bNAbs) combined with Th-epitopes. This is a modified version of a previously designed artificial protein, TBI (T- and B-cell epitopes containing Immunogen), carrying four T- and five B-cell epitopes from HIV-1 Env and Gag proteins. To engineer the nTBI molecule, three B-cell epitopes of the TBI protein were replaced with the epitopes recognized by broadly neutralizing HIV-1 antibodies 10E8, 2F5, and a linear peptide mimic of VRC01 epitope. We showed that immunization of rabbits with the nTBI protein elicited antibodies that recognize HIV-1 proteins and were able to neutralize Env-pseudotyped SF162.LS HIV-1 strain (tier 1). Competition assay revealed that immunization of rabbits with nTBI induced mainly 10E8-like antibodies. Our findings support the use of nTBI protein as an immunogen with predefined favorable antigenic properties.


2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Yuan Gu ◽  
Ximeng Sun ◽  
Jingjing Huang ◽  
Bin Zhan ◽  
Xinping Zhu

Multiepitope peptide vaccine has some advantages over traditional recombinant protein vaccine due to its easy and fast production and possible inclusion of multiple protective epitopes of pathogens. However, it is usually poorly immunogenic and needs to conjugate to a large carrier protein. Peptides conjugated to a central lysine core to form multiple antigen peptides (MAPs) will increase the immunogenicity of peptide vaccine. In this study, we constructed a MAP consisting of CD4+ T cell and B cell epitopes of paramyosin (Pmy) of Trichinella spiralis (Ts-Pmy), which has been proved to be a good vaccine candidate in our previous work. The immunogenicity and induced protective immunity of MAP against Trichinella spiralis (T. spiralis) infection were evaluated in mice. We demonstrated that mice immunized with MAP containing CD4+ T cell and B cell epitopes (MAP-TB) induced significantly higher protection against the challenge of T. spiralis larvae (35.5% muscle larva reduction) compared to the MAP containing B cell epitope alone (MAP-B) with a 12.4% muscle larva reduction. The better protection induced by immunization of MAP-TB was correlated with boosted antibody titers (both IgG1 and IgG2a) and mixed Th1/Th2 cytokine production secreted by the splenocytes of immunized mice. Further flow cytometry analysis of lymphocytes in spleens and draining lymph nodes demonstrated that mice immunized with MAP-TB specifically enhanced the generation of T follicular helper (Tfh) cells and germinal center (GC) B cells, while inhibiting follicular regulatory CD4+ T (Tfr) cells and regulatory T (Treg) cells. Immunofluorescence staining of spleen sections also confirmed that MAP-TB vaccination enhanced the formation of GCs. Our results suggest that CD4+ T cell epitope of Ts-Pmy is crucial in vaccine component for inducing better protection against T. spiralis infection.


2016 ◽  
Author(s):  
Jane Homan ◽  
Robert W Malone ◽  
Steven J Darnell ◽  
Robert D Bremel

The association of Guillain-Barré syndrome with Zika virus infection raises suspicion of autoimmunity in the pathogenesis of Zika associated disease. Using computational analysis to identify predicted B and T cell epitopes, we assessed whether antibodies elicited by B cell epitopes in Zika virus may also target B cell epitopes in the human proteome. We detected amino acid motifs predicted to be B cell epitopes in Zika virus proteins which are also present in human proteins, including pro-neuropeptide Y (proNPY), NAV2 and other proteins with interacting neurophysiologic function. We examine the predicted MHC binding of peptides likely to provide T cell help to the potential mimic epitopes. Some potential mimic epitopes in Zika virus envelope have apparently strong T cell help, likely facilitating immunoglobulin class switch. We also identify epitope mimic commonalities with dengue serotypes 1 and 3. We hypothesize that antibodies to Zika virus epitopes may contribute to the pathogenesis of Zika-associated Guillain-Barré syndrome, microcephaly, and ocular lesions, and may be a driver of autoimmunity. The risk associated with responses to potential epitope mimics must be addressed in the development of vaccines and therapeutics for Zika virus infections.


Author(s):  
Wahiba Ezzemani ◽  
Marc P. Windisch ◽  
Anass Kettani ◽  
Haya Altawalah ◽  
Jalal Nourlil ◽  
...  

Background: Globally, the recent outbreak of Zika virus (ZIKV) in Brazil, Asia Pacific, and other countries highlighted the unmet medical needs. Currently, there are neither effective vaccines nor therapeutics available to prevent or treat ZIKV infection. Objective: In this study, we aimed to design an epitope-based vaccine for ZIKV using an in silico approach to predict and analyze B- and T-cell epitopes. Methods: The prediction of the most antigenic epitopes has targeted the capsid and the envelope proteins as well as nonstructural proteins NS5 and NS3 using immune-informatics tools PROTPARAM, CFSSP, PSIPRED, and Vaxijen v2.0. B and T-cell epitopes were predicted using ABCpred, IEDB, TepiTool, and their toxicity were evaluated using ToxinPred. The 3-dimensional epitope structures were generated by PEP-FOLD. Energy minimization was performed using Swiss-Pdb Viewer, and molecular docking was conducted using PatchDock and FireDock server. Results: As a result, we predicted 307 epitopes of MHCI (major histocompatibility complex class I) and 102 epitopes of MHCII (major histocompatibility complex class II). Based on immunogenicity and antigenicity scores, we identified the four most antigenic MHC I epitopes: MVLAILAFLR (HLA-A*68 :01), ETLHGTVTV (HLA-A*68 :02), DENHPYRTW (HLA-B*44 :02),QEGVFHTMW (HLA-B*44 :03) and TASGRVIEEW (HLA-B*58:01), and MHC II epitopes: IIKKFKKDLAAMLRI (HLA-DRB3*02 :02), ENSKMMLELDPPFGD (HLA-DRB3*01:01), HAETWFFDENHPYRT (HLA-DRB3*01:01), TDGVYRVMTRRLLGS (HLA-DRB1*11 :01), and DGCWYGMEIRPRKEP (HLA-DRB5*01:01). Conclusion : This study provides novel potential B cell and T cell epitopes to fight Zika virus infections and may prompt further development of vaccines against ZIKV and other emerging infectious diseases. However, further investigations for protective immune response by in vitro and in vivo studies to ratify the immunogenicity, safety of the predicted structure, and ultimately the vaccine properties to prevent ZIKV infections are warranted.


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