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Orders Norzivirales and Timlovirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The short epitope 31-DPAFRA-36 (or DPAFR or still DPAF), a hepatocyte-binding domain from the hepatitis B virus preS1 region, served as the first real immunological marker in the first VLP mapping studies and further in the numerous elucidations of different VLP carriers, such as, for example, the hamster polyomavirus major capsid protein VP1 (Gedvilaite et al. 2000; Zvirbliene et al. 2006). This linear epitope was recognized strongly by the classical anti-preS1 monoclonal antibody MA18/7 generated by the famous Wolfram H. Gerlich’s team (Heermann et al. 1984) and mapped to the four minimal DPAF aa residues by the Grēns team (Sominskaya et al. 1992b) and then still to the three letters D, P, and F by the famous Ken Murray’s team (Germaschewski and Murray 1995). When the preS1 epitope DPAFR was inserted as the standard immunological marker at positions 2, 10, and 129 of the fr coat, it appeared in all cases on the particle surface (Borisova et al. 1987). In parallel, the Grēns team used a longer immunological marker, namely the well-known and widely used V3 loop of the envelope gp120 protein of HIV-1 (Goudsmit et al. 1988), in this case, of the strain MN. This model epitope was 39 or 40 aa residues long. Unfortunately, all attempts to tolerate this 40-aa-long V3 loop into the N-terminus, at positions 10, 12, and 15 or within the FG loop, led to unassembled and mostly insoluble products (Kaspars Tārs, unpublished data).
Human Monoclonal Antibodies and Immune Modulation in Viral Hepatitis, Schistosomiasis, and HTLV Infection
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Thomas F. Kresina, Garry A. Neil, Steven K. H. Foung
A number of human monoclonal antibodies specific for hepatitis B virus surface antigen have been generated. In a recent study [51], two human monoclonal antibodies were developed from EBV-transformed B-Iymphocytes derived from individuals with high titers of antisurface antigen antibodies. The transformed lymphocytes underwent large-scale fermentation to produce batch quantities of human monoclonal antibodies. Characterization of the antibody binding epitopes indicated that one antibody bound a conformational epitope, whereas the other bound a linear epitope of hepatitis B surface antigen. Only the latter antibody produces total inhibition of binding of hepatitis B surface antigen subtypes, suggesting potential clinical use. Previous studies had generated a number of human monoclonal antibodies specific for hepatitis B virus surface antigen by a novel method of B cell selection, activation, and clonal expansion in SCID-Hu mice [16]. Immunization of SCID-Hu-peripheral blood lymphocyte (PBL) was followed by generation of anti-hepatitis B surface antigen antibody secretion hybridomas by the method of electro-fusion [16].
Chimeric VLPs
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The short epitope 31-DPAFRA-36 (DPAFR, or still DPAF), a hepatocyte-binding domain from the hepatitis B virus preS1 region, served as the first real immunological marker in the first VLP mapping studies, and further in the numerous elucidations of different VLP carriers, such as, for example, the hamster polyomavirus major capsid protein VP1 (Gedvilaite et al. 2000; Zvirbliene et al. 2006). This linear epitope was recognized strongly by the classical anti-preS1 monoclonal antibody MA18/7 generated by the famous Wolfram H. Gerlich's team (Heermann et al. 1984) and mapped to the four minimal DPAF amino acid residues by Grēns’ team (Sominskaya et al. 1992b) and then still to the three letters D, P, and F by the famous Ken Murray's team (Germaschewski and Murray 1995). When the preS1 epitope DPAFR was inserted as the standard immunological marker at positions 2, 10, and 129 of the fr coat, it appeared in all cases on the particle surface (Borisova et al. 1987). In parallel, Grēns’ team used a longer immunological marker, namely, the well-known and widely used V3 loop of the envelope gp120 protein of human immunodeficiency virus 1, in this case, of the MN subtype (Goudsmit et al. 1988). This model epitope was 39 or 40 amino acid residues long. Unfortunately, all attempts to tolerate this 40-amino acid-long V3 loop into the N-terminus, at positions 10, 12, and 15, or within the FG loop led to unassembled and mostly insoluble products (Kaspars Tārs, unpublished data).
Recent trends in next generation immunoinformatics harnessed for universal coronavirus vaccine design
Published in Pathogens and Global Health, 2023
Chin Peng Lim, Boon Hui Kok, Hui Ting Lim, Candy Chuah, Badarulhisam Abdul Rahman, Abu Bakar Abdul Majeed, Michelle Wykes, Chiuan Herng Leow, Chiuan Yee Leow
An epitope is the part of an antigen that is recognized by the adaptive immune system. It binds to specific receptors including antibodies, MHC molecules and T-cell receptors [28]. The binding portion of an antibody is termed a paratope. Epitopes can be either continuous or discontinuous. A continuous or linear epitope is a relatively short (usually 5–6) amino acid sequences recognized by the paratope of a corresponding antibody. In contrast, a discontinuous epitope consists of non-adjacent segments of amino acids, not necessarily from one chain, which form a specific 3D structure, which can also be recognized by antibodies. Since discontinuous epitope arises from a specific 3D fold, it is also known as conformational epitope. Notably, epitopes recognized by B-cell epitopes may contain lipids, nucleic acids or carbohydrates, giving resultant antibodies a vast repertoire while T-cell epitopes are usually peptide fragments. The investigation, identification and development of epitopes are crucial in promoting the advancement of diagnostics and therapeutics [110].
Progress and challenges for the machine learning-based design of fit-for-purpose monoclonal antibodies
Published in mAbs, 2022
Rahmad Akbar, Habib Bashour, Puneet Rawat, Philippe A. Robert, Eva Smorodina, Tudor-Stefan Cotet, Karine Flem-Karlsen, Robert Frank, Brij Bhushan Mehta, Mai Ha Vu, Talip Zengin, Jose Gutierrez-Marcos, Fridtjof Lund-Johansen, Jan Terje Andersen, Victor Greiff
Many-to-many binding: Antibody-antigen binding is mediated by the interaction of AAs at the paratope–epitope interface of the complex. Antibody binding to the epitope is mainly formed by the three hypervariable regions termed complementarity-determining regions (CDRs) situated in each of the antibody heavy and light chains.43 The CDR3 on the heavy chain (CDR3H) is obligate for epitope binding and is on average 15-17 AAs long.44,45 Given that the diversity of antigens is even larger, the recognition of the majority of antigens encountered is ensured by antibody cross-reactivity, which means they may bind multiple epitopes on different proteins with high affinity.46 Epitope binding is therefore encoded in higher-order complex dependencies (correlations between spatially distant AAs in the CDRH3 enabling the binding of conformational epitopes, allowing a higher combination of binding motifs) in the low dimensionality of the antibody sequence space. These strong dependencies reflect 3D binding, where residues that are distant along the sequence can be close in the folded 3D structure. Indeed, the majority of antibody epitopes are thought to be conformational47 – although 85% of epitopes contain one or several contiguous (linear) epitope stretches.45,48 Therefore, to learn the rules of antibody-antigen binding, approaches need to be developed that untangle the non-linear sequence dependencies that govern the antibody, antigen, and antibody-antigen structures in both bound49,50 and unbound51 states.
Immunoinformatics-guided designing and in silico analysis of epitope-based polyvalent vaccines against multiple strains of human coronavirus (HCoV)
Published in Expert Review of Vaccines, 2022
Bishajit Sarkar, Md. Asad Ullah, Yusha Araf, Nafisa Nawal Islam, Umme Salma Zohora
The epitopes were predicted using the Immune Epitope Database or IEDB (https://www.iedb.org/), which contains a vast collection of experimental data on T-cell epitopes and antibodies [26]. The MHC class-I or CD8+ cytotoxic T-lymphocytic (CTL) epitopes were predicted using the IEDB recommended 2020.04 (NetMHCpan EL 4.0) method . The top MHC class-I epitopes were selected for further analysis. Again, MHC class-II or CD4+ helper T-lymphocytic (HTL) epitopes were predicted using the IEDB Recommended Method 2.2 which gives predictions in percentile scores. The top predicted MHC class-II epitopes were considered for further analysis. The determined MHC class-I epitopes were 9-mers and the MHC class-II epitopes were 15-mers. The HLA alleles for which these predicted epitopes were found, were also noted and listed. B-cell epitopes in a vaccine trigger the antigen-specific immunoglobulin production which are crucial components of adaptive immunity []. The B-cell epitopes of the proteins were predicted by BepiPred linear epitope prediction method [] and the epitopes with more than ten amino acids were considered as potential candidates for vaccine construction. Using a combination of a hidden Markov model and a propensity scale method, BepiPred predicts the location of linear B-cell epitopes [].