scholarly journals Antigenic Evolution of Vaccine-Derived Polioviruses: Changes in Individual Epitopes and Relative Stability of the Overall Immunological Properties

2006 ◽  
Vol 80 (6) ◽  
pp. 2641-2653 ◽  
Author(s):  
Maria L. Yakovenko ◽  
Elena A. Cherkasova ◽  
Gennady V. Rezapkin ◽  
Olga E. Ivanova ◽  
Alexander P. Ivanov ◽  
...  
Keyword(s):  
Amino Acid ◽  
Rational Design ◽  
Driving Forces ◽  
Oral Poliovirus Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Populations ◽  
Amino Acid Residues ◽  
Specific Amino Acid ◽  
Antigenic Sites ◽  
Neutralizing Capacity

ABSTRACT The Sabin oral poliovirus vaccine (OPV) readily undergoes changes in antigenic sites upon replication in humans. Here, a set of antigenically altered descendants of the three OPV serotypes (76 isolates) was characterized to determine the driving forces behind these changes and their biological implications. The amino acid residues of OPV derivatives that lie within or close to the known antigenic sites exhibited a marked tendency to be replaced by residues characteristic of homotypic wild polioviruses, and these changes may occur very early in OPV evolution. The specific amino acid alterations nicely correlated with serotype-specific changes in the reactivity of certain individual antigenic sites, as revealed by the recently devised monoclonal antibody-based enzyme-linked immunosorbent assay. In comparison to the original vaccine, small changes, if any, in the neutralizing capacity of human or rabbit sera were observed in highly diverged vaccine polioviruses of three serotypes, in spite of strong alterations of certain epitopes. We propose that the common antigenic alterations in evolving OPV strains largely reflect attempts to eliminate fitness-decreasing mutations acquired either during the original selection of the vaccine or already present in the parental strains. Variability of individual epitopes does not appear to be primarily caused by, or lead to, a significant immune evasion, enhancing only slightly, if at all, the capacity of OPV derivatives to overcome immunity in human populations. This study reveals some important patterns of poliovirus evolution and has obvious implications for the rational design of live viral vaccines.

scholarly journals Hemin-Binding Proteins as Potent Markers for Serological Diagnosis of Infections with Bartonella quintana

2013 ◽  
Vol 20 (4) ◽  
pp. 620-626 ◽  
Author(s):  
Mayumi Matsuoka ◽  
Toshinori Sasaki ◽  
Naomi Seki ◽  
Mutsuo Kobayashi ◽  
Kyoko Sawabe ◽  
...  
Keyword(s):  
Amino Acid ◽  
Synthetic Peptides ◽  
Homeless People ◽  
Enzyme Linked Immunosorbent Assay ◽  
Deletion Mutants ◽  
Amino Acid Residues ◽  
Content Type ◽  
Bartonella Quintana ◽  
Antigenic Sites ◽  
Indirect Immunofluorescent

ABSTRACTIt is difficult to distinguish infections with differentBartonellaspecies using commercially available immunofluorescence (indirect immunofluorescent antibody [IFA]) assay kits. To identify appropriate proteins for serodiagnosis ofBartonella quintanainfections, we investigated the antigenicity ofB. quintanaproteins using sera from homeless people with highB. quintanaIgG titers in IFA assay. These sera reacted strongly to an outer membrane protein, hemin-binding protein D (HbpD). Further, serum from an endocarditis patient infected withB. quintanareacted to HbpB and HbpD. To locate the antigenic sites within the proteins, we generated deletion mutants of HbpB and HbpD. Amino acid residues 89 to 220 of HbpB and 151 to 200 of HbpD were identified as the minimum regions required for recognition by these sera. Several oligopeptides comprising parts of the minimum regions of HbpB and HbpD were synthesized, and their immunoreactivity with the above-mentioned sera was tested by enzyme-linked immunosorbent assay (ELISA). Serum from the endocarditis patient reacted similarly to synthetic peptides HbpB2 (amino acid residues 144 to 173 of HbpB) and HbpD3 (151 to 200 residues of HbpD), while sera from the other subjects reacted to HbpD3. These results indicate that synthetic peptides HbpB2 and HbpD3 might be suitable for developing serological tools for differential diagnosis ofB. quintanainfections from otherBartonellainfections.

scholarly journals Rational design of novel amphipathic antimicrobial peptides focused on the distribution of cationic amino acid residues

MedChemComm ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 896-900 ◽  
Author(s):  
Takashi Misawa ◽  
Chihiro Goto ◽  
Norihito Shibata ◽  
Motoharu Hirano ◽  
Yutaka Kikuchi ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Amino Acid ◽  
Human Cell ◽  
Hemolytic Activity ◽  
Rational Design ◽  
Cell Cytotoxicity ◽  
Amino Acid Residues ◽  
High Antimicrobial Activity ◽  
Cationic Amino Acid ◽  
Helical Peptide

Amphipathic helical peptideStripeshowed high antimicrobial activity, low hemolytic activity, and low human cell cytotoxicity.

scholarly journals Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

2014 ◽  
Vol 95 (5) ◽  
pp. 1104-1116 ◽  
Author(s):  
Amin S. Asfor ◽  
Sasmita Upadhyaya ◽  
Nick J. Knowles ◽  
Donald P. King ◽  
David J. Paton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Guinea Pig ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Residues ◽  
Serotype O ◽  
Antigenic Sites ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
The Impact

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.

scholarly journals Investigation of major amino acid residues of anti-norfloxacin monoclonal antibodies responsible for binding with fluoroquinolones

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patamalai Boonserm ◽  
Songchan Puthong ◽  
Thanaporn Wichai ◽  
Sajee Noitang ◽  
Pongsak Khunrae ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
3D Structure ◽  
Cross Reactivity ◽  
Enzyme Linked Immunosorbent Assay ◽  
Amino Acid Residues ◽  
Variable Regions ◽  
Complementarity Determining Regions ◽  
Crucial Part ◽  
Major Amino Acid

AbstractIt is important to understand the amino acid residues that govern the properties of the binding between antibodies and ligands. We studied the binding of two anti-norfloxacins, anti-nor 132 and anti-nor 155, and the fluoroquinolones norfloxacin, enrofloxacin, ciprofloxacin, and ofloxacin. Binding cross-reactivities tested by an indirect competitive enzyme-linked immunosorbent assay indicated that anti-nor 132 (22–100%) had a broader range of cross-reactivity than anti-nor 155 (62–100%). These cross-reactivities correlated with variations in the numbers of interacting amino acid residues and their positions. Molecular docking was employed to investigate the molecular interactions between the fluoroquinolones and the monoclonal antibodies. Homology models of the heavy chain and light chain variable regions of each mAb 3D structure were docked with the fluoroquinolones targeting the crucial part of the complementarity-determining regions. The fluoroquinolone binding site of anti-nor 155 was a region of the HCDR3 and LCDR3 loops in which hydrogen bonds were formed with TYR (H:35), ASN (H:101), LYS (H:106), ASN (L:92), and ASN (L:93). These regions were further away in anti-nor 132 and could not contact the fluoroquinolones. Another binding region consisting of HIS (L:38) and ASP (H:100) was found for norfloxacin, enrofloxacin, and ciprofloxacin, whereas only ASP (H:100) was found for ofloxacin.

scholarly journals Genetic Diversity of the cagA gene of Helicobacter pylori strains from Sudanese Patients with Different Gastroduodenal Diseases

2019 ◽  
Author(s):  
Hadeel Gassim Hassan ◽  
Abeer Babiker Idris ◽  
Mohamed A. Hassan ◽  
Hisham N. Altayb ◽  
Kyakonye Yasin ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Amino Acid ◽  
Novel Mutation ◽  
Amino Acid Residues ◽  
Specific Amino Acid ◽  
Gastrointestinal Malignancy ◽  
High Incidence ◽  
H Pylori ◽  
High Level ◽  
Chloride Method

AbstractBackgroundThere is an increase in the prevalence of Helicobacter pylori infection in Sudan, accompanied by a high incidence of upper gastrointestinal malignancy. The cytotoxin-associated gene cagA gene is a marker of a pathogenicity island (PAI) in H. pylori and plays a crucial role in determining the clinical outcome of Helicobacter infections.ObjectiveThis study aimed to determine the frequency and heterogeneity of the cagA gene of H. pylori and correlate the presence of cagA gene with clinical outcomes.Materials and methodsFifty endoscopy biopsies were collected from Fedail and Soba hospitals in Khartoum state. DNA was extracted using the Guanidine chloride method followed by PCR to amplify 16S rRNA and cagA gene of H. pylori using specific primers. DNA amplicons of cagA gene were purified and sequenced. Bioinformatics and statistical analysis were done to characterize and to test the association between cagA gene and gastric complications.ResultsCagA gene was detected in 20/37(54%) of the samples that were found positive for H. pylori. There was no association between endoscopy finding and the presence of the cagA gene (p = 0.225). Specific amino acid variations were found at seven loci related to strains from a patient with duodenitis, gastric ulcer, and gastric atrophy (R448H, T457K, S460L, IT463-464VA, D470E, A482Q, KNV490-491-492TKT) while mutations in cancerous strain were A439P, T457P, and H500Y.ConclusionDisease-specific variations of cagA of H. pylori strains, in the region of amino acid residues 428-510, were evident among Sudanese patients with different gastroduodenal diseases. A novel mutation (K458N) was detected in a patient with duodenitis, which affects the positive electrostatic surface of cagA. Phylogenetic analysis showed a high level of diversity of cagA from Sudanese H. pylori strains.

scholarly journals Efficient Synthesis of Rare Disaccharides by Engineered β-Glucosidase Based on Hydropathy Index

2020 ◽  
Author(s):  
Kangle Niu ◽  
Zhengyao Liu ◽  
Yuhui Feng ◽  
Tianlong Gao ◽  
Zhenzhen Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Rational Design ◽  
Large Scale ◽  
Catalytic Site ◽  
Scale Production ◽  
Total Production ◽  
Amino Acid Residues ◽  
Hydropathy Index ◽  
Reverse Hydrolysis ◽  
Hydrolysis Activity

<p>Oligosaccharides have important therapeutic applications. A useful route for oligosaccharides synthesis, especially rare disaccharides, is reverse hydrolysis by <i>β</i>-glucosidase. However, the low conversion efficiency of disaccharides from monosaccharides limits its large-scale production because the equilibrium is biased in the direction of hydrolysis. Based on the analysis of the docking results, we hypothesized that the hydropathy index of key amino acid residues in the catalytic site is closely related with disaccharide synthesis and more hydrophilic residues located in the catalytic site would enhance reverse hydrolysis activity. In this study, positive variants<i> Tr</i>Cel1b<sup>I177S</sup>, <i>Tr</i>Cel1b<sup>I177S/I174S</sup>, and <i>Tr</i>Cel1b<sup>I177S/I174S/W173H</sup>, and one negative variant <i>Tr</i>Cel1b<sup>N240I</sup> were designed according to the <u>H</u>ydropathy <u>I</u>ndex <u>F</u>or <u>E</u>nzyme <u>A</u>ctivity (HIFEA) strategy. The reverse hydrolysis with <i>Tr</i>Cel1b<sup>I177S/I174S/W173H </sup>was accelerated and then the maximum total production (<a>195.8 mg/ml/mg enzyme</a>) of the synthesized disaccharides was increased 3.5-fold compared to that of wildtype. On the contrary, <a><i>Tr</i>Cel1b</a><sup>N240I</sup> lost reverse hydrolysis activity. The results demonstrate that<a> </a><a>the average hydropathy index</a> of <a>the key amino acid residues </a>in the catalytic site of<i> Tr</i>Cel1b is an important factor for the synthesis of laminaribiose, sophorose, and cellobiose. The HIFEA strategy provides a new perspective for the rational design of <i>β</i>-glucosidases used for the synthesis of oligosaccharides.</p>

scholarly journals Location of antigenic sites recognized by monoclonal antibodies in the influenza A virus nucleoprotein molecule

2009 ◽  
Vol 90 (7) ◽  
pp. 1730-1733 ◽  
Author(s):  
Natalia L. Varich ◽  
Konstantin S. Kochergin-Nikitsky ◽  
Evgeny V. Usachev ◽  
Olga V. Usacheva ◽  
Alexei G. Prilipov ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
Influenza A Virus ◽  
Influenza A ◽  
Antigenic Variation ◽  
Strain Differences ◽  
Antigenic Structure ◽  
Amino Acid Residues ◽  
Mutant Proteins ◽  
Antigenic Sites

The locations of amino acid positions relevant to antigenic variation in the nucleoprotein (NP) of influenza virus are not conclusively known. We analysed the antigenic structure of influenza A virus NP by introducing site-specific mutations at amino acid positions presumed to be relevant for the differentiation of strain differences by anti-NP monoclonal antibodies. Mutant proteins were expressed in a prokaryotic system and analysed by performing ELISA with monoclonal antibodies. Four amino acid residues were found to determine four different antibody-binding sites. When mapped in a 3D X-ray model of NP, the four antigenically relevant amino acid positions were found to be located in separate physical sites of the NP molecule.

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