scholarly journals DENV-Mimetic Polymersome Nanoparticles Bearing Multi-Epitope Lipopeptides Antigen as the Next-Generation Dengue Vaccine

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 156
Author(s):  
Nur Adilah Abdul Rahman ◽  
Abdin Shakirin Mohamad Norpi ◽  
Muhammad Luqman Nordin ◽  
Mohd Cairul Iqbal Mohd Amin ◽  
Abdullah Al-Hadi Ahmad Fuaad ◽  
...  
Keyword(s):  
Histopathological Examination ◽  
Peptide Vaccine ◽  
Vaccine Delivery ◽  
Denv Infection ◽  
Cell Mediated Immunity ◽  
Dengue Vaccine ◽  
Structural Morphology ◽  
M Proteins ◽  
Structural Trait ◽  
Delivery Platform

Dengue remains a severe threat to public health. The safety and efficacy of the licensed dengue vaccine is not clinically satisfactory, which necessitate the need of new approach in designing an effective dengue vaccine without eliciting adverse reaction. Herein, we have designed a lipidated multi-epitope peptide vaccine (LipoDV) that can elicit highly targeted humoral and cell-mediated immune responses. To improve its immunogenicity, LipoDV was presented on the surface of MPLA-functionalized polymersome nanoparticles (PNs-LipoDV-MPLA). The as-constructed vaccine delivery platform resembles the structural morphology of DENV owing to its spherical nanoscale particle size and surface immunostimulatory properties given by LipoDV and MPLA that emulating the functional role of DENV E and prM/M proteins respectively. A proof-of-concept study demonstrated that BALB/c mice immunized with PNs-LipoDV-MPLA induced a stronger antigen-specific antibody response with an enhanced cell-mediated immunity as characterized by the elevated IFN-γ secretion in comparison to other tested vaccine candidates which possess a lesser structural trait of DENV. The DENV-mimicking nanoparticles vaccine exhibited negligible toxicity as analyzed by hemolytic test, MTT assay, histopathological examination and abnormal toxicity test on immunized mice. Collectively, our study provides a strong foundation in designing an effective peptide-based vaccine delivery platform against DENV infection.

scholarly journals Development of Peptide Vaccines in Dengue

2018 ◽  
Vol 24 (11) ◽  
pp. 1157-1173 ◽  
Author(s):  
Kavita Reginald ◽  
Yanqi Chan ◽  
Magdalena Plebanski ◽  
Chit Laa Poh
Keyword(s):  
T Cell ◽  
Neutralizing Antibodies ◽  
Peptide Vaccine ◽  
Human Leukocyte ◽  
Cost Effective ◽  
Cell Mediated Immunity ◽  
T Cell Epitopes ◽  
Peptide Vaccines ◽  
Dengue Vaccine ◽  
Region Data

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.

scholarly journals Immunoinformatics and Structural Analysis for Identification of Immunodominant Epitopes in SARS-CoV-2 as Potential Vaccine Targets

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 290 ◽  
Author(s):  
Sumit Mukherjee ◽  
Dmitry Tworowski ◽  
Rajesh Detroja ◽  
Sunanda Biswas Mukherjee ◽  
Milana Frenkel-Morgenstern
Keyword(s):  
Peptide Vaccine ◽  
Vaccine Design ◽  
Computational Prediction ◽  
Effective Vaccine ◽  
Cell Mediated Immunity ◽  
T Cell Epitopes ◽  
Protective Antigens ◽  
Global Pandemic ◽  
Time Required ◽  
Immunodominant Epitopes

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.

Scientific consultation on cell mediated immunity (CMI) in dengue and dengue vaccine development

Vaccine ◽  
2009 ◽  
Vol 27 (3) ◽  
pp. 355-368 ◽  
Author(s):  
Stephen J. Thomas ◽  
Joachim Hombach ◽  
Alan Barrett
Keyword(s):  
Vaccine Development ◽  
Cell Mediated Immunity ◽  
Dengue Vaccine

scholarly journals Complexity of Neutralizing Antibodies against Multiple Dengue Virus Serotypes after Heterotypic Immunization and Secondary Infection Revealed by In-Depth Analysis of Cross-Reactive Antibodies

2015 ◽  
Vol 89 (14) ◽  
pp. 7348-7362 ◽  
Author(s):  
Wen-Yang Tsai ◽  
Anna Durbin ◽  
Jih-Jin Tsai ◽  
Szu-Chia Hsieh ◽  
Stephen Whitehead ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Secondary Infection ◽  
Denv Infection ◽  
Primary Immunization ◽  
Dengue Vaccine ◽  
Alternative Strategies ◽  
Live Attenuated Vaccines ◽  
Human Sera ◽  
Arboviral Diseases

ABSTRACTThe four serotypes of dengue virus (DENV) cause the most important and rapidly emerging arboviral diseases in humans. The recent phase 2b and 3 studies of a tetravalent dengue vaccine reported a moderate efficacy despite the presence of neutralizing antibodies, highlighting the need for a better understanding of neutralizing antibodies in polyclonal human sera. Certain type-specific (TS) antibodies were recently discovered to account for the monotypic neutralizing activity and protection after primary DENV infection. The nature of neutralizing antibodies after secondary DENV infection remains largely unknown. In this study, we examined sera from 10 vaccinees with well-documented exposure to first and second DENV serotypes through heterotypic immunization with live-attenuated vaccines. Higher serum IgG avidities to both exposed and nonexposed serotypes were found after secondary immunization than after primary immunization. Using a two-step depletion protocol to remove different anti-envelope antibodies, including group-reactive (GR) and complex-reactive (CR) antibodies separately, we found GR and CR antibodies together contributed to more than 50% of neutralizing activities against multiple serotypes after secondary immunization. Similar findings were demonstrated in patients after secondary infection. Anti-envelope antibodies recognizing previously exposed serotypes consisted of a large proportion of GR antibodies, CR antibodies, and a small proportion of TS antibodies, whereas those recognizing nonexposed serotypes consisted of GR and CR antibodies. These findings have implications for sequential heterotypic immunization or primary immunization of DENV-primed individuals as alternative strategies for DENV vaccination. The complexity of neutralizing antibodies after secondary infection provides new insights into the difficulty of their application as surrogates of protection.IMPORTANCEThe four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Despite the presence of neutralizing antibodies, a moderate efficacy was recently reported in phase 2b and 3 trials of a dengue vaccine; a better understanding of neutralizing antibodies in polyclonal human sera is urgently needed. We studied vaccinees who received heterotypic immunization of live-attenuated vaccines, as they were known to have received the first and second DENV serotype exposures. We found anti-envelope antibodies consist of group-reactive (GR), complex-reactive (CR), and type-specific (TS) antibodies, and that both GR and CR antibodies contribute significantly to multitypic neutralizing activities after secondary DENV immunization. These findings have implications for alternative strategies for DENV vaccination. Certain TS antibodies were recently discovered to contribute to the monotypic neutralizing activity and protection after primary DENV infection; our findings of the complexity of neutralizing activities after secondary immunization/infection provide new insights for neutralizing antibodies as surrogates of protection.

scholarly journals A Computational Assay to Design an Epitope-Based Peptide Vaccine against Saint Louis Encephalitis Virus

2013 ◽  
Vol 7 ◽  
pp. BBI.S13402 ◽  
Author(s):  
Anayet Hasan ◽  
Mehjabeen Hossain ◽  
Jibran Alam
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Peptide Vaccine ◽  
Encephalitis Virus ◽  
Peptide Sequence ◽  
Cell Mediated Immunity ◽  
Protein Database ◽  
Saint Louis ◽  
Saint Louis Encephalitis

Saint Louis encephalitis virus, a member of the flaviviridae subgroup, is a culex mosquito-borne pathogen. Despite severe epidemic outbreaks on several occasions, not much progress has been made with regard to an epitope-based vaccine designed for Saint Louis encephalitis virus. The envelope proteins were collected from a protein database and analyzed with an in silico tool to identify the most immunogenic protein. The protein was then verified through several parameters to predict the T-cell and B-cell epitopes. Both T-cell and B-cell immunity were assessed to determine that the protein can induce humoral as well as cell-mediated immunity. The peptide sequence from 330–336 amino acids and the sequence REYCYEATL from the position 57 were found as the most potential B-cell and T-cell epitopes, respectively. Furthermore, as an RNA virus, one important thing was to establish the epitope as a conserved one; this was also done by in silico tools, showing 63.51% conservancy. The epitope was further tested for binding against the HLA molecule by computational docking techniques to verify the binding cleft epitope interaction. However, this is a preliminary study of designing an epitope-based peptide vaccine against Saint Louis encephalitis virus; the results awaits validation by in vitro and in vivo experiments.

A paradigm for peptide vaccine delivery using viral epitopes encapsulated in degradable polymer hydrogel capsules

Biomaterials ◽  
2009 ◽  
Vol 30 (28) ◽  
pp. 5178-5186 ◽  
Author(s):  
Siow-Feng Chong ◽  
Amy Sexton ◽  
Robert De Rose ◽  
Stephen J. Kent ◽  
Alexander N. Zelikin ◽  
...  
Keyword(s):  
Peptide Vaccine ◽  
Vaccine Delivery ◽  
Polymer Hydrogel ◽  
Degradable Polymer ◽  
Hydrogel Capsules

scholarly journals Immuno-informatics Design of a Multimeric Epitope Peptide Based Vaccine Targeting SARS-CoV-2 Spike Glycoprotein

2020 ◽  
Author(s):  
Onyeka S. Chukwudozie ◽  
Clive M. Gray ◽  
Tawakalt A. Fagbayi ◽  
Rebecca C. Chukwuanukwu ◽  
Victor O. Oyebanji ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Peptide Vaccine ◽  
Spike Protein ◽  
Cell Mediated Immunity ◽  
Epitope Peptide ◽  
Mhc I ◽  
B Cell Epitopes ◽  
Antibody Recognition

ABSTRACTDeveloping an efficacious vaccine to SARS-CoV-2 infection is critical to stem COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in the design of an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers along with 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC-I and II alleles respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. The vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, with triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We therefore propose that potential vaccine designs consider this approach.

scholarly journals An agent-based model of dengue virus transmission shows how multiple uncertainties about vaccine efficacy influence public health impact projections

2016 ◽  
Author(s):  
T. Alex Perkins ◽  
Robert C. Reiner ◽  
Guido España ◽  
Quirine A. ten Bosch ◽  
Amit Verma ◽  
...  
Keyword(s):  
Public Health ◽  
Dengue Virus ◽  
Vaccine Efficacy ◽  
Denv Infection ◽  
Health Impact ◽  
Public Health Impact ◽  
Statistical Uncertainty ◽  
Dengue Vaccine ◽  
Agent Based ◽  
Biological Uncertainty

ABSTRACTGiven the limited effectiveness of strategies based solely on vector control to reduce dengue virus (DENV) transmission, it is expected that an effective vaccine could play a pivotal role in reducing the global disease burden of dengue. Of several dengue vaccines under development, Dengvaxia® from Sanofi Pasteur recently became the first to become licensed in select countries and to achieve WHO recommendation for use in certain settings, despite the fact that a number of uncertainties about its profile complicate projections of its public health impact. We used a stochastic, agent-based model for DENV transmission to perform simulations of the public health impact of dengue vaccines in light of two key uncertainties: (1) “statistical uncertainty” about the numerical value of the vaccine’s efficacy against disease, and (2) “biological uncertainty” about the extent to which its efficacy against disease derives from the amelioration of symptoms, blocking of DENV infection, or some combination thereof. Simulations of a generic dengue vaccine showed that the proportion of disease episodes averted following 20 years of routine vaccination of nine-year olds at 80% coverage was sensitive to both the numerical value of vaccine efficacy and to the extent to which efficacy derives from blocking of DENV infection. Simulations of a vaccine resembling Dengvaxia® took into account that vaccine trial results substantially reduced statistical uncertainty but did not address biological uncertainty, resulting in the proportion of disease episodes averted being more sensitive to biological uncertainty than to statistical uncertainty. Taken together, our results indicate limitations associated with the use of symptomatic disease as the primary endpoint of dengue vaccine trials and highlight the importance of considering multiple forms of uncertainty in projections of a vaccine’s public health impact.

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