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Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies1, 2, 3. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine. Subject terms:
Immunology
At a glance
Figures First | 1-4 of 4 | Last left
1. PGT antibodies.
a, Median neutralization potency against viruses neutralized with an IC50<50gml1. b, Neutralization breadth at different IC50 cut-offs.
2.
Figure 2: Key monoclonal antibodies fully recapitulate serum neutralization by the corresponding donor serum. Serum breadth was correlated with the breadth of the broadest monoclonal antibody (mAb) for each donor (percentage of viruses neutralized at 50% neutralizing titre (NT50)>100 or IC50<50gml1, respectively). Of note, monoclonal antibodies isolated from donor 39 could not completely recapitulate the serum neutralization breadth.
3.
Figure 3: Epitope mapping of PGT antibodies. a, Competition of PGT monoclonal antibodies with sCD4 (soluble CD4), b12 (anti-CD4 binding site), 2G12 (anti-glycan), F425/b4e8 (anti-V3), X5 (CD4-induced), PG9 (anti-V1/V2 and V3, quaternary) and each other. Competition assays were performed by ELISA using gp120Bal or gp120JR-FL, except for the PG9 competition assay, which was performed on the surface of JRFLE168K or JR-CSF transfected cells. Boxes are coded as follows: +++, 75100% competition; ++, 5075% competition; +, 2550% competition; , <25% competition. Experiments were performed in duplicate, and data represent an average of at least two independent experiments. b, Glycan microarray analysis (Consortium for Functional Glycomics (CFG), version 5.0) reveals that PGT monoclonal antibodies 125, 126, 127, 128 and 130 contact Man8 (313), Man8GlcNAc2 (193), Man9 (314) and Man9GlcNAc2 (194) glycans directly. Only glycan structures with RFU (relative fluorescent units) > 3,000 are shown. PGT-131 showed no detectable binding to the CFG glycan array but bound to Man9-oligodendrons30 (data not shown). Error bars represent standard deviation. c, d, Binding of PGT monoclonal antibodies 125, 126, 127, 128 and 130 to gp120 is competed by Man9 oligodendrons but not Man4 oligodendrons. Binding of 131 to immobilized gp120 was too low to measure any competition. Error bars represent standarmean.
Figure 4: Certain antibodies or antibody combinations are able to cover a broad range of HIV isolates at low, vaccine-achievable concentrations.
a, Cumulative frequency distribution of IC50 values of broadly neutralizing monoclonal antibodies tested against a 162-virus panel. The y-axis shows the cumulative frequency of IC50 values up to the concentration shown on the x-axis and can therefore also be interpreted as the breadth at a specific IC50 cut-off. b, c, Percentage of viruses covered by single monoclonal antibodies (solid lines) or by at least one of the monoclonal antibodies in dual combinations of breadth (dashed black lines) dependent on individual concentrations. The grey area in both panels is the coverage of 26 monoclonal antibodies tested on the 162-virus panel (PGT121123, PGT125 128, PGT130131, PGT135137, PGT141145, PG9, PG16, PGC14, VRC01, PGV04, b12, 2G12, 4E10, 2F5) and depicts the theoretical maximal achievable coverage known to date. right
Phylogenetic tree with the two main viral lineages indicated; group 1 is circled in blue and group 2 is circled in green. Strains from subtypes circled in red are bound or neutralized by C05.
2.
Figure 2: C05 protects mice from lethal virus challenge. a, b, Survival and weight loss were monitored in response to varying amounts of C05 IgG administered prophylactically to mice 24h before challenge with 25 the 50% mouse lethal dose (MLD50) of A/Memphis/3/2008 (H1N1) (a) or 33 MLD50 of A/X-31/1968 (H3N2) viruses (b). c, d, A single therapeutic dose of 15mgkg1 C05 IgG was delivered 1, 2, 3, 4 or 5 days post-infection (DPI) with 25 MLD50 of A/Memphis/3/2008 (c) or 33 MLD50 of A/X-31/1968 viruses (d). n = 5 mice for all studies. Error bars denote s.d.
3.
Neutralization
Table of Contents 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 1. Introduction 2. Determining What is a Strong Acid or Strong Base 3. Strong Acid-Strong Base Neutralization 4. Weak Acid-Weak Base Neutralization 5. pH Levels at the Equivalence Point 6. Titration 7. Problems 8. Solutions 9. References 10. Contributors
A neutralization reaction is when an acid and a base react to form water and a salt and involves the combination of H+ ions and OH- ions to generate water. The neutralization of a strong acid and strong base has a pH equal to 7. The neutralization of a strong acid and weak base will have a pH of less than 7, and conversely, the resulting pH when a strong base neutralizes a weak acid will be greater than 7.
Introduction
When a solution is neutralized, it means that salts are formed from equal weights of acid and base. The amount of acid needed is the amount that would give one mole of protons (H+) and the amount of base needed is the amount that would give one mole of (OH-). Because salts are formed from neutralization reactions with equivalent concentrations of weights of acids and bases: N parts of acid will always neutralize N parts of base.
This is a list of the most common strong acids and bases. Most everything elso not in this table is considered to be weak.
Strong Acids HCl HBr HI HCIO4 HNO3 Strong Bases LiOH NaOH KOH RbOH CsOH Ca(OH)2 Sr(OH)2 Ba(OH)2
A weak acid, weak base reaction can be shown by the net ionic equation example:
Stomach Antacids:
Antacids are supposed to decrease the amount of hydrochloric acid in the stomach by reacting with excess acid. They are use in the treatment of gastric hyperacidity and peptic ulcers. Som of the ingredients in antacids are: Magnesia (MgO), milk of magnesia (Mg(OH)2, calcium carbonate (CaCO3), sodium bicarbonate (NaHCO3), dihydroxyaluminum sodium carbonat (NaAl(OH)2CO3), aluminum hydroxide gel (Al(OH)3). Severa of these will habe top be recognized as Bronsted bases.
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