Displaying publications 1 - 20 of 30 in total

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  1. An immunogenic epitope of Chlamydia pneumoniae from a random phage display peptide library is reactive with both monoclonal antibody and patients sera
    Naidu BR, Ngeow YF, Wang LF, Chan L, Yao ZJ, Pang T
    Immunol Lett, 1998 Jun;62(2):111-5.
    PMID: 9698107
    Random 15-mer peptides displayed on filamentous phages were screened in binding studies using a Chlamydia pneumoniae-specific monoclonal antibody (RR-402) and affinity-purified, polyclonal sera from patients seropositive for C. pneumoniae infections by the microimmunofluorescence (MIF) test. One 15-mer epitope, epitope Cpnl5A (LASLCNPKPSDAPVT) was identified in both the monoclonal and polyclonal screenings, and showed higher ELISA reactivity with C. pneumoniae MIF-positive sera compared to patients with other chlamydial infections, non-chlamydial respiratory infections and normal healthy sera (MIF-negative). Interestingly, epitope Cpnl5A also showed significant (52%) amino acid sequence homology to the 56 kDa type-specific antigen of Rickettsia tsutsugamushi, a protein implicated in the virulence of this organism.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology*
  2. Fulltext Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera
    Chua CL, Sam IC, Merits A, Chan YF
    PLoS Negl Trop Dis, 2016 08;10(8):e0004960.
    PMID: 27571254 DOI: 10.1371/journal.pntd.0004960
    BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood.

    METHODOLOGY/PRINCIPAL FINDINGS: We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008-2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes.

    CONCLUSION/SIGNIFICANCE: Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.

    Matched MeSH terms: Epitopes, B-Lymphocyte/genetics; Epitopes, B-Lymphocyte/immunology*
  3. Antigenicity and immunogenicity of the immunodominant region of hepatitis B surface antigen displayed on bacteriophage T7
    Tan GH, Yusoff K, Seow HF, Tan WS
    J Med Virol, 2005 Dec;77(4):475-80.
    PMID: 16254965
    The immunodominant region of hepatitis B virus (HBV) located in the viral small surface antigen (S-HBsAg) elicits virus-neutralizing and protective antibodies. In order to develop an easy and inexpensive method to produce this region without the need for extensive purification, amino acid residues 111-156 of S-HBsAg were fused to the C-terminal end of the 10B capsid protein of T7 phage. Western blotting and ELISA confirmed the expression of the recombinant protein on the surface of the phage particles. The recombinant phage exhibited the antigenic and immunogenic characteristics of HBsAg, illustrating its potential as an immunological reagent and vaccine.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology
  4. Characterisation of mouse monoclonal antibodies targeting linear epitopes on Chikungunya virus E2 glycoprotein
    Chua CL, Chan YF, Sam IC
    J Virol Methods, 2014 Jan;195:126-33.
    PMID: 24134938 DOI: 10.1016/j.jviromet.2013.10.015
    Chikungunya virus (CHIKV) is a mosquito-borne arbovirus which has recently re-emerged globally and poses a major threat to public health. Infection leads to severe arthralgia, and disease management remains supportive in the absence of vaccines and anti-viral interventions. The high specificities of monoclonal antibodies (mAbs) have been exploited in immunodiagnostics and immunotherapy in recent decades. In this study, eight different clones of mAbs were generated and characterised. These mAbs targeted the linear epitopes on the CHIKV E2 envelope glycoprotein, which is the major target antigen during infection. All the mAbs showed binding activity against the purified CHIKV virion or recombinant E2 when analysed by immunofluorescence, ELISA and Western blot. The epitopes of each mAb were mapped by overlapping synthetic peptide-based ELISA. The epitopes are distributed at different functional domains of E2 glycoprotein, namely at domain A, junctions of β-ribbons with domains A and B, and domain C. Alignment of mAb epitope sequences revealed that some are well-conserved within different genotypes of CHIKV, while some are identical to and likely to cross-react with the closely-related alphavirus O'nyong-nyong virus. These mAbs with their mapped epitopes are useful for the development of diagnostic or research tools, including immunofluorescence, ELISA and Western blot.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology*
  5. Computational design of a new multi-epitope vaccine using immunoinformatics approach against mastitis disease
    Dzayee SA, Khudhur PK, Mahmood A, Markov A, Maseleno A, Ebrahimpour Gorji A
    Anim Biotechnol, 2022 Nov;33(6):1359-1370.
    PMID: 33761829 DOI: 10.1080/10495398.2021.1899937
    Mastitis disease causes significant economic losses in dairy farms by reducing milk production, increasing production costs, and reducing milk quality. Streptococcus agalactiae continues to be a major cause of mastitis in dairy cattle. To date, there has been no approved multi-epitope vaccine against this pathogen in the market. In the present study, an efficient multi-epitope vaccine against S. agalactiae, the causative agent of mastitis, was designed using various immonoinformtics approaches. Potential epitopes were selected from Sip protein to improve vaccine immunogenicity. The designed vaccine is more antigenic in nature. Then, linkers and profilin adjuvant were added to enhance the immunity of vaccines. The designed vaccine was evaluated in terms of molecular weight, PI, immunogenicity, Toxicity, and allergenicity. Prediction of three-dimensional (3 D) structure of multi-epitope vaccine, followed by refinement and validation, was conducted to obtain a high-quality 3 D structure of the designed multi-epitope vaccine. The designed vaccine was then subjected to molecular docking with Toll-like receptor 11 (TLR11) receptor to evaluate its binding efficiency followed by dynamic simulation for stable interaction. In silico cloning approach was carried out to improve the expression of the vaccine construct. These analyses indicate that the designed multi-epitope vaccine may produce particular immune responses against S. agalactiae and may be further helpful to control mastitis after in vitro and in vivo immunological assays.
    Matched MeSH terms: Epitopes, B-Lymphocyte/chemistry
  6. Fulltext Delineation of B-cell Epitopes of Salmonella enterica serovar Typhi Hemolysin E: Potential antibody therapeutic target
    Chin CF, Lai JY, Choong YS, Anthony AA, Ismail A, Lim TS
    Sci Rep, 2017 05 19;7(1):2176.
    PMID: 28526816 DOI: 10.1038/s41598-017-01987-8
    Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein. The predicted linear GAAAGIVAG and conformational epitope PYSQESVLSADSQNQK were further validated against the pooled sera. The identified epitopes were then used to isolate epitope specific monoclonal antibodies by antibody phage display. Monoclonal scFv antibodies were enriched for both linear and conformational epitopes. Molecular docking was performed to elucidate the antigen-antibody interaction of the monoclonal antibodies against the epitopes on the HlyE monomer and oligomer structure. An in-depth view of the mechanistic and positional characteristics of the antibodies and epitope for HlyE was successfully accomplished by a combination of phage display and bioinformatic analysis. The predicted function and structure of the antibodies highlights the possibility of utilizing the antibodies as neutralizing agents for typhoid fever.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology*; Epitopes, B-Lymphocyte/chemistry
  7. Design of a multi-epitope subunit vaccine candidate for chikungunya virus using computational methodology
    Tongco AMP, Rivera WL
    Trop Biomed, 2023 Jun 01;40(2):129-137.
    PMID: 37650398 DOI: 10.47665/tb.40.2.002
    Chikungunya virus (CHIKV) is a neglected tropical pathogen that causes fever and long-lasting severe arthralgia. Despite its high morbidity, there is still no licensed specific therapeutic option for it. This study proposes a multi-epitope subunit vaccine candidate for CHIKV, designed using computational methods. It was based on the E2 spike glycoprotein in CHIKV, from which T- and B-cell epitopes were predicted and then refined. The pan HLA DR-binding epitope (PADRE) was added to this refined construct, then simulated compared with the native protein, where it was predicted to elicit more than twice the number of antibody titers. Thus, this construct is potentially effective against CHIKV, which further experimentation using live models would be able to verify. This study also demonstrates the feasibility of using rational tools in the future to further optimize vaccine design.
    Matched MeSH terms: Epitopes, B-Lymphocyte
  8. Designing and evaluation of an antibody-targeted chimeric recombinant vaccine encoding Shigella flexneri outer membrane antigens
    Kazi A, Hisyam Ismail CMK, Anthony AA, Chuah C, Leow CH, Lim BH, et al.
    Infect Genet Evol, 2020 06;80:104176.
    PMID: 31923724 DOI: 10.1016/j.meegid.2020.104176
    Shigellosis is one of the most common diseases found in the developing countries, especially those countries that are prone flood. The causative agent for this disease is the Shigella species. This organism is one of the third most common enteropathogens responsible for childhood diarrhea. Since Shigella can survive gastric acidity and is an intracellular pathogen, it becomes difficult to treat. Also, uncontrolled use of antibiotics has led to development of resistant strains which poses a threat to public health. Therefore, there is a need for long term control of Shigella infection which can be achieved by designing a proper and effective vaccine. In this study, emphasis was made on designing a candidate that could elicit both B-cell and T-cell immune response. Hence B- and T-cell epitopes of outer membrane channel protein (OM) and putative lipoprotein (PL) from S. flexneri 2a were computationally predicted using immunoinformatics approach and a chimeric construct (chimeric-OP) containing the immunogenic epitopes selected from OM and PL was designed, cloned and expressed in E. coli system. The immunogenicity of the recombinant chimeric-OP was assessed using Shigella antigen infected rabbit antibody. The result showed that the chimeric-OP was a synthetic peptide candidate suitable for the development of vaccine and immunodiagnostics against Shigella infection.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology; Epitopes, B-Lymphocyte/chemistry
  9. Fulltext Development of multi-epitope peptide-based vaccines against SARS-CoV-2
    Lim HX, Lim J, Jazayeri SD, Poppema S, Poh CL
    Biomed J, 2021 03;44(1):18-30.
    PMID: 33727051 DOI: 10.1016/j.bj.2020.09.005
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic involving so far more than 22 million infections and 776,157 deaths. Effective vaccines are urgently needed to prevent SARS-CoV-2 infections. No vaccines have yet been approved for licensure by regulatory agencies. Even though host immune responses to SARS-CoV-2 infections are beginning to be unravelled, effective clearance of virus will depend on both humoral and cellular immunity. Additionally, the presence of Spike (S)-glycoprotein reactive CD4+ T-cells in the majority of convalescent patients is consistent with its significant role in stimulating B and CD8+ T-cells. The search for immunodominant epitopes relies on experimental evaluation of peptides representing the epitopes from overlapping peptide libraries which can be costly and labor-intensive. Recent advancements in B- and T-cell epitope predictions by bioinformatic analysis have led to epitope identifications. Assessing which peptide epitope can induce potent neutralizing antibodies and robust T-cell responses is a prerequisite for the selection of effective epitopes to be incorporated in peptide-based vaccines. This review discusses the roles of B- and T-cells in SARS-CoV-2 infections and experimental validations for the selection of B-, CD4+ and CD8+ T-cell epitopes which could lead to the construction of a multi-epitope peptide vaccine. Peptide-based vaccines are known for their low immunogenicity which could be overcome by incorporating immunostimulatory adjuvants and nanoparticles such as Poly Lactic-co-Glycolic Acid (PLGA) or chitosan.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology*
  10. Enterovirus-Specific Anti-peptide Antibodies
    Poh CL, Kirk K, Chua HN, Grollo L
    Methods Mol Biol, 2015;1348:341-50.
    PMID: 26424285 DOI: 10.1007/978-1-4939-2999-3_29
    Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13.
    Matched MeSH terms: Epitopes, B-Lymphocyte
  11. Fulltext Exploiting reverse vaccinology approach for the design of a multiepitope subunit vaccine against the major SARS-CoV-2 variants
    Campos DMO, Silva MKD, Barbosa ED, Leow CY, Fulco UL, Oliveira JIN
    Comput Biol Chem, 2022 Dec;101:107754.
    PMID: 36037724 DOI: 10.1016/j.compbiolchem.2022.107754
    The current COVID-19 pandemic, an infectious disease caused by the novel coronavirus (SARS-CoV-2), poses a threat to global health because of its high rate of spread and death. Currently, vaccination is the most effective method to prevent the spread of this disease. In the present study, we developed a novel multiepitope vaccine against SARS-CoV-2 containing Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (BA.1) variants. To this end, we performed a robust immunoinformatics approach based on multiple epitopes of the four structural proteins of SARS-CoV-2 (S, M, N, and E) from 475 SARS-CoV-2 genomes sequenced from the regions with the highest number of registered cases, namely the United States, India, Brazil, France, Germany, and the United Kingdom. To investigate the best immunogenic epitopes for linear B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL), we evaluated antigenicity, allergenicity, conservation, immunogenicity, toxicity, human population coverage, IFN-inducing, post-translational modifications, and physicochemical properties. The tertiary structure of a vaccine prototype was predicted, refined, and validated. Through docking experiments, we evaluated its molecular coupling to the key immune receptor Toll-Like Receptor 3 (TLR3). To improve the quality of docking calculations, quantum mechanics/molecular mechanics calculations (QM/MM) were used, with the QM part of the simulations performed using the density functional theory formalism (DFT). Cloning and codon optimization were performed for the successful expression of the vaccine in E. coli. Finally, we investigated the immunogenic properties and immune response of our SARS-CoV-2 multiepitope vaccine. The results of the simulations show that administering our prototype three times significantly increases the antibody response and decreases the amount of antigens. The proposed vaccine candidate should therefore be tested in clinical trials for its efficacy in neutralizing SARS-CoV-2.
    Matched MeSH terms: Epitopes, B-Lymphocyte
  12. Fulltext Genetic diversity and in silico analysis of Plasmodium knowlesi Serine Repeat Antigen (SERA) 3 antigen 2 in Malaysia
    Tan JH, Ding HX, Fong MY, Lau YL
    Infect Genet Evol, 2023 Oct;114:105490.
    PMID: 37595939 DOI: 10.1016/j.meegid.2023.105490
    Plasmodium knowlesi is the leading cause of malaria in Malaysia. Serine Repeat Antigens (SERAs) have an essential role in the parasite life cycle. However, genetic characterization on P. knowlesi SERA3 Ag2 (PkSERA3 Ag2) is lacking. In the present study, nucleotide diversity, natural selection, and haplotypes of PkSERA3 Ag2 in clinical samples from Peninsular Malaysia and Malaysian Borneo were investigated. A total of 50 P. knowlesi clinical samples were collected from Peninsular Malaysia and Malaysian Borneo. The PkSERA3 Ag2 gene was amplified using PCR, and subsequently cloned and sequenced. Genetic diversity, haplotype, natural selection as well as genetic structure and differentiation of PkSERA3 Ag2 were analysed. In addition, in silico analyses were performed to identify repeat motifs, B-cell epitopes, and antigenicity indices of the protein. Analysis of 114 PkSERA3 Ag2 sequences revealed high nucleotide diversity of the gene in Malaysia. A codon-based Z-test indicated that the gene underwent purifying selection. Haplotype and population structure analyses identified two distinct PkSERA3 Ag2 clusters (K = 2, ΔK = 721.14) but no clear genetic distinction between PkSERA3 Ag2 from Peninsular Malaysia and Malaysian Borneo. FST index indicated moderate differentiation of the gene. In silico analyses revealed unique repeat motifs among PkSERA3 Ag2 isolates. Moreover, the amino acid sequence of PkSERA3 Ag2 exhibited potential B-cell epitopes and possessed high antigenicity indices. These findings enhance the understanding of PkSERA3 Ag2 gene as well as its antigenic properties. Further validation is necessary to ascertain the utility of PkSERA3 Ag2 as a serological marker for P. knowlesi infection.
    Matched MeSH terms: Epitopes, B-Lymphocyte/genetics; Epitopes, B-Lymphocyte/metabolism
  13. Identification and selection of immunodominant B and T cell epitopes for dengue multi-epitope-based vaccine
    Lim HX, Lim J, Poh CL
    Med Microbiol Immunol, 2021 Feb;210(1):1-11.
    PMID: 33515283 DOI: 10.1007/s00430-021-00700-x
    Dengue virus (DENV) comprises four serotypes (DENV1-4) which cause 390 million global infections with 500,000 hospitalizations and 25,000 fatalities annually. Currently, the only FDA approved DENV vaccine is the chimeric live-attenuated vaccine, Dengvaxia®, which is based on the yellow fever virus (YFV) genome that carries the prM and E genes of the respective DENV 1, 2, 3, and 4 serotypes. However, it has lower efficacies against serotypes DENV1 (51%) and DENV2 (34%) when compared with DENV3 (75%) and DENV4 (77%). The absence of T cell epitopes from non-structural (NS) and capsid (C) proteins of the yellow fever vaccine strain might have prevented Dengvaxia® to elicit robust cellular immune responses, as CD8+ T cell epitopes are mainly localized in the NS3 and NS5 regions. Multi-epitope-based peptide vaccines carrying CD4+, CD8+ T cell and B cell epitopes represent a novel approach to generate specific immune responses. Therefore, assessing and selecting epitopes that can induce robust B and T cell responses is a prerequisite for constructing an efficient multi-epitope peptide vaccine. Potent B and T cell epitopes can be identified by utilizing immunoinformatic analysis, but the immunogenicity of the epitopes have to be experimentally validated. In this review, we presented T cell epitopes that have been predicted by bioinformatic approaches as well as recent experimental validations of CD4+ and CD8+ T cell epitopes by ex-vivo stimulation of PBMCs with specific peptides. Immunoproteomic analysis could be utilized to uncover HLA-specific epitopes presented by DENV-infected cells. Based on various approaches, immunodominant epitopes capable of inducing strong immune responses could be selected and incorporated to form a universally applicable multi-epitope-based peptide dengue vaccine.
    Matched MeSH terms: Epitopes, B-Lymphocyte/genetics; Epitopes, B-Lymphocyte/immunology*
  14. Immunogenic epitopes of Salmonella typhi GroEL heat shock protein reactive with both monoclonal antibody and patients sera
    Panchanathan V, Naidu BR, Devi S, Di Pasquale A, Mason T, Pang T
    Immunol Lett, 1998 Jun;62(2):105-9.
    PMID: 9698106
    A series of 122, 9-mer overlapping peptides based on the sequence of the Salmonella typhi GroEL gene was synthesized on the surfaces of polyethylene pins and screened with monoclonal antibody to GroEL and with human sera from patients with typhoid fever and normal healthy blood donors. Three immunogenic epitopes corresponding to peptides EGQDRGYSY, YSYNKETGE and GKGTEEKEK were identified upon screening with the human sera. In addition, screening of the peptides with a monoclonal antibody to GroEL detected binding to a third peptide, KGGKGTEEK, which contains a common overlapping sequence to peptide GKGTEEKEK. Identification and definition of these epitopes will be important in delineating the biological and immunological functions of this protein and in designing better diagnostic tests and vaccines.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology*
  15. Fulltext Immunogenicity of recombinant Mycobacterium bovis bacille Calmette-Guèrin clones expressing T and B cell epitopes of Mycobacterium tuberculosis antigens
    Mohamud R, Azlan M, Yero D, Alvarez N, Sarmiento ME, Acosta A, et al.
    BMC Immunol, 2013;14 Suppl 1:S5.
    PMID: 23458635 DOI: 10.1186/1471-2172-14-S1-S5
    Recombinant Mycobacterium bovis bacille Calmette-Guèrin (rBCG) expressing three T cell epitopes of Mycobacterium tuberculosis (MTB) Ag85B antigen (P1, P2, P3) fused to the Mtb8.4 protein (rBCG018) or a combination of these antigens fused to B cell epitopes from ESAT-6, CFP-10 and MTP40 proteins (rBCG032) were used to immunize Balb/c mice. Total IgG responses were determined against Mtb8.4 antigen and ESAT-6 and CFP-10 B cell epitopes after immunization with rBCG032. Mice immunized with rBCG032 showed a significant increase in IgG1 and IgG2a antibodies against ESAT-6 and MTP40 (P1) B cell epitopes and IgG3 against both P1 and P2 B cell epitopes of MPT40. Splenocytes from mice immunized with rBCG018 proliferated against Ag85B P2 and P3 T cell epitopes and Mtb8.4 protein whereas those from mice-immunized with rBCG032 responded against all Ag85B epitopes and the ESAT-6 B cell epitope. CD4⁺ and CD8⁺ lymphocytes from mice immunized with rBCG018 produced primarily Th1 type cytokines in response to the T cell epitopes. Similar pattern of recognition against the T cell epitopes were obtained with rBCG032 with the additional recognition of ESAT-6, CFP-10 and one of the MTP40 B cell epitopes with the same pattern of cytokines. This study demonstrates that rBCG constructs expressing either T or T and B cell epitopes of MTB induced appropriate immunogenicity against MTB.
    Matched MeSH terms: Epitopes, B-Lymphocyte/biosynthesis; Epitopes, B-Lymphocyte/immunology*
  16. Immunoinformatics study on highly expressed Mycobacterium tuberculosis genes during infection
    Nguyen Thi le T, Sarmiento ME, Calero R, Camacho F, Reyes F, Hossain MM, et al.
    Tuberculosis (Edinb), 2014 Sep;94(5):475-81.
    PMID: 25034135 DOI: 10.1016/j.tube.2014.06.004
    The most important targets for vaccine development are the proteins that are highly expressed by the microorganisms during infection in-vivo. A number of Mycobacterium tuberculosis (Mtb) proteins are also reported to be expressed in-vivo at different phases of infection. In the present study, we analyzed multiple published databases of gene expression profiles of Mtb in-vivo at different phases of infection in animals and humans and selected 38 proteins that are highly expressed in the active, latent and reactivation phases. We predicted T- and B-cell epitopes from the selected proteins using HLAPred for T-cell epitope prediction and BCEPred combined with ABCPred for B-cell epitope prediction. For each selected proteins, regions containing both T- and B-cell epitopes were identified which might be considered as important candidates for vaccine design against tuberculosis.
    Matched MeSH terms: Epitopes, B-Lymphocyte/genetics*
  17. Immunoinformatics-based potential multi-peptide vaccine designing against Jamestown Canyon Virus (JCV) capable of eliciting cellular and humoral immune responses
    Shahab M, Aiman S, Alshammari A, Alasmari AF, Alharbi M, Khan A, et al.
    Int J Biol Macromol, 2023 Dec 31;253(Pt 2):126678.
    PMID: 37666399 DOI: 10.1016/j.ijbiomac.2023.126678
    Jamestown Canyon virus (JCV) is a deadly viral infection transmitted by various mosquito species. This mosquito-borne virus belongs to Bunyaviridae family, posing a high public health threat in the in tropical regions of the United States causing encephalitis in humans. Common symptoms of JCV include fever, headache, stiff neck, photophobia, nausea, vomiting, and seizures. Despite the availability of resources, there is currently no vaccine or drug available to combat JCV. The purpose of this study was to develop an epitope-based vaccine using immunoinformatics approaches. The vaccine aimed to be secure, efficient, bio-compatible, and capable of stimulating both innate and adaptive immune responses. In this study, the protein sequence of JCV was obtained from the NCBI database. Various bioinformatics methods, including toxicity evaluation, antigenicity testing, conservancy analysis, and allergenicity assessment were utilized to identify the most promising epitopes. Suitable linkers and adjuvant sequences were used in the design of vaccine construct. 50s ribosomal protein sequence was used as an adjuvant at the N-terminus of the construct. A total of 5 CTL, 5 HTL, and 5 linear B cell epitopes were selected based on non-allergenicity, immunological potential, and antigenicity scores to design a highly immunogenic multi-peptide vaccine construct. Strong interactions between the proposed vaccine and human immune receptors, i.e., TLR-2 and TLR-4, were revealed in a docking study using ClusPro software, suggesting their possible relevance in the immunological response to the vaccine. Immunological and physicochemical properties assessment ensured that the proposed vaccine demonstrated high immunogenicity, solubility and thermostability. Molecular dynamics simulations confirmed the strong binding affinities, as well as dynamic and structural stability of the proposed vaccine. Immune simulation suggest that the vaccine has the potential to effectively stimulate cellular and humoral immune responses to combat JCV infection. Experimental and clinical assays are required to validate the results of this study.
    Matched MeSH terms: Epitopes, B-Lymphocyte
  18. Immunoinformatics-driven In silico vaccine design for Nipah virus (NPV): Integrating machine learning and computational epitope prediction
    Shahab M, Iqbal MW, Ahmad A, Alshabrmi FM, Wei DQ, Khan A, et al.
    Comput Biol Med, 2024 Mar;170:108056.
    PMID: 38301512 DOI: 10.1016/j.compbiomed.2024.108056
    The Nipah virus (NPV) is a highly lethal virus, known for its significant fatality rate. The virus initially originated in Malaysia in 1998 and later led to outbreaks in nearby countries such as Bangladesh, Singapore, and India. Currently, there are no specific vaccines available for this virus. The current work employed the reverse vaccinology method to conduct a comprehensive analysis of the entire proteome of the NPV virus. The aim was to identify and choose the most promising antigenic proteins that could serve as potential candidates for vaccine development. We have also designed B and T cell epitopes-based vaccine candidate using immunoinformatics approach. We have identified a total of 5 novel Cytotoxic T Lymphocytes (CTL), 5 Helper T Lymphocytes (HTL), and 6 linear B-cell potential antigenic epitopes which are novel and can be used for further vaccine development against Nipah virus. Then we performed the physicochemical properties, antigenic, immunogenic and allergenicity prediction of the designed vaccine candidate against NPV. Further, Computational analysis indicated that these epitopes possessed highly antigenic properties and were capable of interacting with immune receptors. The designed vaccine were then docked with the human immune receptors, namely TLR-2 and TLR-4 showed robust interaction with the immune receptor. Molecular dynamics simulations demonstrated robust binding and good dynamics. After numerous dosages at varied intervals, computational immune response modeling showed that the immunogenic construct might elicit a significant immune response. In conclusion, the immunogenic construct shows promise in providing protection against NPV, However, further experimental validation is required before moving to clinical trials.
    Matched MeSH terms: Epitopes, B-Lymphocyte/chemistry
  19. Immunological characterization of rice tungro spherical virus coat proteins and differentiation of isolates from the Philippines and India
    Druka A, Burns T, Zhang S, Hull R
    J Gen Virol, 1996 Aug;77 ( Pt 8):1975-83.
    PMID: 8760450
    Rice tungro spherical virus (RTSV) has an RNA genome of more than 12 kb with various features which classify it as a plant picornavirus. The capsid comprises three coat protein (CP) species, CP1, CP2 and CP3, with predicted molecular masses of 22.5, 22.0 and 33 kDa, respectively, which are cleaved from a polyprotein. In order to obtain information on the properties of these proteins, each was expressed in E. coli, purified as a fusion to the maltose-binding protein and used for raising a polyclonal antiserum. CP1, CP2 and CP3 with the expected molecular masses were detected specifically in virus preparations. CP3 is probably the major antigenic determinant on the surface of RTSV particles, as was shown by ELISA, Western blotting and immunogold electron microscopy using antisera obtained against whole virus particles and to each CP separately. In some cases, especially in crude extracts, CP3 antiserum detected several other proteins (40-42 kDa), which could be products of CP3 post-translational modification. No serological differences were detected between the three CPs from isolates from the Philippines, Thailand, Malaysia and India. The CP3-related 40-42 kDa proteins of the Indian RTSV isolate have a slightly higher electrophoretic mobility (42-44 kDa) and a different response to cellulolytic enzyme preparations, which allows them to be differentiated from south-east Asian isolates.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology
  20. In Silico-Guided Sequence Modification of Epitopes in Cancer Vaccine Development
    Hoo WPY, Siak PY, In LLA
    Methods Mol Biol, 2020;2131:213-228.
    PMID: 32162256 DOI: 10.1007/978-1-0716-0389-5_10
    Discovery of tumor antigenic epitopes is important for cancer vaccine development. Such epitopes can be designed and modified to become more antigenic and immunogenic in order to overcome immunosuppression towards the native tumor antigen. In silico-guided modification of epitope sequences allows predictive discrimination of those that may be potentially immunogenic. Therefore, only candidates predicted with high antigenicity will be selected, constructed, and tested in the lab. Here, we described the employment of in silico tools using a multiparametric approach to assess both potential T-cell epitopes (MHC class I/II binding) and B-cell epitopes (hydrophilicity, surface accessibility, antigenicity, and linear epitope). A scoring and ranking system based on these parameters was developed to shortlist potential mimotope candidates for further development as peptide cancer vaccines.
    Matched MeSH terms: Epitopes, B-Lymphocyte/immunology
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