Anti-V3 Monoclonal Antibodies Display Broad Neutralizing Activities against Multiple HIV-1 Subtypes
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{"title"=>"Anti-V3 monoclonal antibodies display broad neutralizing activities against multiple HIV-1 subtypes", "type"=>"journal", "authors"=>[{"first_name"=>"Catarina E.", "last_name"=>"Hioe", "scopus_author_id"=>"6603706708"}, {"first_name"=>"Terri", "last_name"=>"Wrin", "scopus_author_id"=>"6701659114"}, {"first_name"=>"Michael S.", "last_name"=>"Seaman", "scopus_author_id"=>"7006600859"}, {"first_name"=>"Xuesong", "last_name"=>"Yu", "scopus_author_id"=>"35199398500"}, {"first_name"=>"Blake", "last_name"=>"Wood", "scopus_author_id"=>"35199325800"}, {"first_name"=>"Steve", "last_name"=>"Self", "scopus_author_id"=>"34572681000"}, {"first_name"=>"Constance", "last_name"=>"Williams", "scopus_author_id"=>"56693441200"}, {"first_name"=>"Miroslaw K.", "last_name"=>"Gorny", "scopus_author_id"=>"7006228733"}, {"first_name"=>"Susan", "last_name"=>"Zolla-Pazner", "scopus_author_id"=>"7006077941"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "doi"=>"10.1371/journal.pone.0010254", "pui"=>"359482228", "sgr"=>"77954110431", "pmid"=>"20421997", "scopus"=>"2-s2.0-77954110431"}, "id"=>"edc6903d-089b-330a-8d89-72ee796e7c33", "abstract"=>"BACKGROUND: The V3 loop of the HIV-1 envelope (Env) glycoprotein gp120 was identified as the \"principal neutralizing domain\" of HIV-1, but has been considered too variable to serve as a neutralizing antibody (Ab) target. Structural and immunochemical data suggest, however, that V3 contains conserved elements which explain its role in binding to virus co-receptors despite its sequence variability. Despite this evidence of V3 conservation, the ability of anti-V3 Abs to neutralize a significant proportion of HIV-1 isolates from different subtypes (clades) has remained controversial.\\n\\nMETHODS: HIV-1 neutralization experiments were conducted in two independent laboratories to test human anti-V3 monoclonal Abs (mAbs) against pseudoviruses (psVs) expressing Envs of diverse HIV-1 subtypes from subjects with acute and chronic infections. Neutralization was defined by 50% inhibitory concentrations (IC(50)), and was statistically assessed based on the area under the neutralization titration curves (AUC).\\n\\nRESULTS: Using AUC analyses, statistically significant neutralization was observed by >or=1 anti-V3 mAbs against 56/98 (57%) psVs expressing Envs of diverse subtypes, including subtypes A, AG, B, C and D. Even when the 10 Tier 1 psVs tested were excluded from the analysis, significant neutralization was detected by >or=1 anti-V3 mAbs against 46/88 (52%) psVs from diverse HIV-1 subtypes. Furthermore, 9/24 (37.5%) Tier 2 viruses from the clade B and C standard reference panels were neutralized by >or=1 anti-V3 mAbs. Each anti-V3 mAb tested was able to neutralize 28-42% of the psVs tested. By IC(50) criteria, 40/98 (41%) psVs were neutralized by >or=1 anti-V3 mAbs.\\n\\nCONCLUSIONS: Using standard and new statistical methods of data analysis, 6/7 anti-V3 human mAbs displayed cross-clade neutralizing activity and revealed that a significant proportion of viruses can be neutralized by anti-V3 Abs. The new statistical method for analysis of neutralization data provides many advantages to previously used analyses.", "link"=>"http://www.mendeley.com/research/antiv3-monoclonal-antibodies-display-broad-neutralizing-activities-against-multiple-hiv1-subtypes", "reader_count"=>32, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>7, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>11, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>18, "Medicine and Dentistry"=>4, "Immunology and Microbiology"=>4}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>18}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/853500"], "description"=>"<p>Seven anti-V3 mAbs were tested against HIV-1 psVs in the TZM.bl experiment. The titration curves observed against nine selected viruses are shown. The background neutralization observed with the irrelevant control mAb 860 is also shown for comparison. Curve fitting was performed using the polynomial regression (quadratic) model described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010254#s2\" target=\"_blank\">Materials and Methods</a>. Fifty percent neutralization is denoted by the dashed line.</p>", "links"=>[], "tags"=>["curves", "anti-v3", "mabs", "hiv-1", "psvs", "tested"], "article_id"=>523949, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.g005", "stats"=>{"downloads"=>1, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neutralization_curves_of_anti_V3_mAbs_against_representative_HIV_1_psVs_tested_using_the_TZM_bl_target_cell_line_/523949", "title"=>"Neutralization curves of anti-V3 mAbs against representative HIV-1 psVs tested using the TZM.bl target cell line.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:45:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/853337"], "description"=>"<p>AUC values were estimated from the titration curves as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010254#s2\" target=\"_blank\">Materials and Methods</a> section. Statistically significant neutralization at p<0.001 is color-coded according to the designated scale.</p>", "links"=>[], "tags"=>["auc", "anti-v3", "mabs", "57", "hiv-1", "pseudoviruses", "tested", "u87"], "article_id"=>523774, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.g004", "stats"=>{"downloads"=>2, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_AUC_values_of_anti_V3_mAbs_against_57_HIV_1_pseudoviruses_tested_using_the_U87_target_cell_line_/523774", "title"=>"The AUC values of anti-V3 mAbs against 57 HIV-1 pseudoviruses tested using the U87 target cell line.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:44:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/853205"], "description"=>"<p>The IC<sub>50</sub> values were estimated from the titration curves of all mAb/psV combinations and are highlighted according to the color-coded scale. Pseudoviruses expressing Envs of JRCSF, NL3.4, and SF162 were tested as positive controls, whereas the irrelevant anti-parvovirus mAb 860 and aMLV Env-expressing psV were used as negative controls. When 50% neutralization was not achieved at the highest mAb concentration tested (50 µg/ml), the IC<sub>50</sub> values are shown as >50.</p>", "links"=>[], "tags"=>["anti-v3", "mabs", "57", "hiv-1", "pseudoviruses", "tested", "u87"], "article_id"=>523643, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.g003", "stats"=>{"downloads"=>1, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_IC_50_values_of_anti_V3_mAbs_against_57_HIV_1_pseudoviruses_tested_using_the_U87_target_cell_line_/523643", "title"=>"The IC<sub>50</sub> values of anti-V3 mAbs against 57 HIV-1 pseudoviruses tested using the U87 target cell line.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:44:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/852955"], "description"=>"<p>The neutralization curves of anti-V3 mAb 2191 against nine selected HIV-1 pseudoviruses are shown with their corresponding AUC and IC<sub>50</sub> values. Fifty percent neutralization is denoted by the dashed line. Significant neutralization at the confidence level of p<0.001 (denoted with * after AUC values) was determined statistically based on comparison with the AUC values of the negative controls together with the slopes of the titration curves as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010254#s2\" target=\"_blank\">Materials and Methods</a>. For viruses coming from patients where the date of infection is known, viruses are denoted as coming from acutely- or chronically-infected patients, and the clade of the virus is denoted by the capital letter in its name (A, B, C or D).</p>", "links"=>[], "tags"=>["neutralization", "hiv-1", "pseudoviruses", "mab", "2191", "u87"], "article_id"=>523400, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.g001", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_neutralization_of_nine_HIV_1_pseudoviruses_by_mAb_2191_using_U87_as_target_cells_/523400", "title"=>"The neutralization of nine HIV-1 pseudoviruses by mAb 2191 using U87 as target cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:42:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/853070"], "description"=>"<p>Seven anti-V3 mAbs (2191, 2219, 2557, 2558, 3074, 3869, and 447) were tested for neutralization against HIV-1 pseudoviruses using the U87 cell line as target cells. MAb 860, specific for parvovirus, and a pseudovirus expressing the aMLV Env were used as negative controls in this assay. The titration curves from eight selected psVs and the aMLV psV control are shown. Curve fitting was performed using the polynomial regression (quadratic) model described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010254#s2\" target=\"_blank\">Materials and Methods</a>. Fifty percent neutralization is denoted by the dashed line. Virus nomenclature is denoted as described in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010254#pone-0010254-g001\" target=\"_blank\">Figure 1</a>.</p>", "links"=>[], "tags"=>["curves", "anti-v3", "mabs", "hiv-1", "psvs", "tested", "u87"], "article_id"=>523508, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.g002", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Neutralization_curves_of_anti_V3_mAbs_against_representative_HIV_1_psVs_tested_using_the_U87_target_cell_/523508", "title"=>"Neutralization curves of anti-V3 mAbs against representative HIV-1 psVs tested using the U87 target cell.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:43:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/853819"], "description"=>"<p>The AUC values were calculated from the titration curves as described in the <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0010254#s2\" target=\"_blank\">Materials and Methods</a> section. All mAb/psV pairs with statistically significant neutralization at p<0.001 are color-coded according to the designated scale. The irrelevant anti-parvovirus mAb 1418 was used together with three other control mAbs (data not shown) as negative controls.</p>", "links"=>[], "tags"=>["auc", "anti-v3", "mabs", "41", "hiv-1", "pseudoviruses", "tested"], "article_id"=>524258, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.g007", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_AUC_values_of_anti_V3_mAbs_against_41_HIV_1_pseudoviruses_tested_using_the_TZM_bl_target_cell_line_/524258", "title"=>"The AUC values of anti-V3 mAbs against 41 HIV-1 pseudoviruses tested using the TZM.bl target cell line.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:47:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/853965"], "description"=>"<p>nd – not determined.</p><p>PA – protective antigen of anthrax.</p><p>§– Gorny et al., unpublished data.</p>", "links"=>[], "tags"=>["mabs"], "article_id"=>524417, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Characteristics_of_human_mAbs_used_for_this_study_/524417", "title"=>"Characteristics of human mAbs used for this study.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:48:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/854007"], "description"=>"<p>*Positive neutralization defined by p<0.001 in AUC analysis with ≥1 anti-V3 mAb(s).</p>", "links"=>[], "tags"=>["psv", "neutralization", "anti", "v3"], "article_id"=>524450, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.t002", "stats"=>{"downloads"=>3, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Summary_of_data_on_psV_neutralization_by_anti_V3_mAbs_/524450", "title"=>"Summary of data on psV neutralization by anti V3 mAbs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-21 01:48:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/853686"], "description"=>"<p>The IC<sub>50</sub> values were estimated from the titration curves of all mAb/psV combinations and are shown with the color-coded scale. When 50% neutralization was not achieved at the highest mAb concentration tested (50 µg/ml), the IC<sub>50</sub> values are shown as >50. Four different irrelevant mAbs (860, 1418, 3685, and 3706) were used as negative controls in this experiment with comparable results, but only the mAb 860 data are shown.</p>", "links"=>[], "tags"=>["anti-v3", "mabs", "41", "hiv-1", "pseudoviruses", "tested", "u87"], "article_id"=>524129, "categories"=>["Immunology", "Infectious Diseases", "Medicine"], "users"=>["Catarina E. Hioe", "Terri Wrin", "Michael S. Seaman", "Xuesong Yu", "Blake Wood", "Steve Self", "Constance Williams", "Miroslaw K. Gorny", "Susan Zolla-Pazner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0010254.g006", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_IC_50_values_of_anti_V3_mAbs_against_41_HIV_1_pseudoviruses_tested_using_the_U87_target_cell_line_/524129", "title"=>"The IC<sub>50</sub> values of anti-V3 mAbs against 41 HIV-1 pseudoviruses tested using the U87 target cell line.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-21 01:46:43"}

PMC Usage Stats | Further Information

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