Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges

Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protect...
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Autor*in:	Siqi Gong [verfasserIn] Samir K. Lakhashe [verfasserIn] Dinesh Hariraju [verfasserIn] Hanna Scinto [verfasserIn] Antonio Lanzavecchia [verfasserIn] Elisabetta Cameroni [verfasserIn] Davide Corti [verfasserIn] Sarah J. Ratcliffe [verfasserIn] Kenneth A. Rogers [verfasserIn] Peng Xiao [verfasserIn] Jane Fontenot [verfasserIn] François Villinger [verfasserIn] Ruth M. Ruprecht [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 12(2021)
Übergeordnetes Werk:	volume:12 ; year:2021

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2021.705592

Katalog-ID:	DOAJ057706441

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520			\|a Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition.
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allfields	10.3389/fimmu.2021.705592 doi (DE-627)DOAJ057706441 (DE-599)DOAJ46765fdad160479eb7819948e8f76c25 DE-627 ger DE-627 rakwb eng RC581-607 Siqi Gong verfasserin aut Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition. dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion Immunologic diseases. Allergy Siqi Gong verfasserin aut Samir K. Lakhashe verfasserin aut Dinesh Hariraju verfasserin aut Dinesh Hariraju verfasserin aut Hanna Scinto verfasserin aut Hanna Scinto verfasserin aut Antonio Lanzavecchia verfasserin aut Antonio Lanzavecchia verfasserin aut Elisabetta Cameroni verfasserin aut Elisabetta Cameroni verfasserin aut Davide Corti verfasserin aut Davide Corti verfasserin aut Sarah J. Ratcliffe verfasserin aut Kenneth A. Rogers verfasserin aut Kenneth A. Rogers verfasserin aut Peng Xiao verfasserin aut Jane Fontenot verfasserin aut François Villinger verfasserin aut François Villinger verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.705592 kostenfrei https://doaj.org/article/46765fdad160479eb7819948e8f76c25 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.705592/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021
spelling	10.3389/fimmu.2021.705592 doi (DE-627)DOAJ057706441 (DE-599)DOAJ46765fdad160479eb7819948e8f76c25 DE-627 ger DE-627 rakwb eng RC581-607 Siqi Gong verfasserin aut Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition. dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion Immunologic diseases. Allergy Siqi Gong verfasserin aut Samir K. Lakhashe verfasserin aut Dinesh Hariraju verfasserin aut Dinesh Hariraju verfasserin aut Hanna Scinto verfasserin aut Hanna Scinto verfasserin aut Antonio Lanzavecchia verfasserin aut Antonio Lanzavecchia verfasserin aut Elisabetta Cameroni verfasserin aut Elisabetta Cameroni verfasserin aut Davide Corti verfasserin aut Davide Corti verfasserin aut Sarah J. Ratcliffe verfasserin aut Kenneth A. Rogers verfasserin aut Kenneth A. Rogers verfasserin aut Peng Xiao verfasserin aut Jane Fontenot verfasserin aut François Villinger verfasserin aut François Villinger verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.705592 kostenfrei https://doaj.org/article/46765fdad160479eb7819948e8f76c25 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.705592/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021
allfields_unstemmed	10.3389/fimmu.2021.705592 doi (DE-627)DOAJ057706441 (DE-599)DOAJ46765fdad160479eb7819948e8f76c25 DE-627 ger DE-627 rakwb eng RC581-607 Siqi Gong verfasserin aut Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition. dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion Immunologic diseases. Allergy Siqi Gong verfasserin aut Samir K. Lakhashe verfasserin aut Dinesh Hariraju verfasserin aut Dinesh Hariraju verfasserin aut Hanna Scinto verfasserin aut Hanna Scinto verfasserin aut Antonio Lanzavecchia verfasserin aut Antonio Lanzavecchia verfasserin aut Elisabetta Cameroni verfasserin aut Elisabetta Cameroni verfasserin aut Davide Corti verfasserin aut Davide Corti verfasserin aut Sarah J. Ratcliffe verfasserin aut Kenneth A. Rogers verfasserin aut Kenneth A. Rogers verfasserin aut Peng Xiao verfasserin aut Jane Fontenot verfasserin aut François Villinger verfasserin aut François Villinger verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.705592 kostenfrei https://doaj.org/article/46765fdad160479eb7819948e8f76c25 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.705592/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021
allfieldsGer	10.3389/fimmu.2021.705592 doi (DE-627)DOAJ057706441 (DE-599)DOAJ46765fdad160479eb7819948e8f76c25 DE-627 ger DE-627 rakwb eng RC581-607 Siqi Gong verfasserin aut Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition. dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion Immunologic diseases. Allergy Siqi Gong verfasserin aut Samir K. Lakhashe verfasserin aut Dinesh Hariraju verfasserin aut Dinesh Hariraju verfasserin aut Hanna Scinto verfasserin aut Hanna Scinto verfasserin aut Antonio Lanzavecchia verfasserin aut Antonio Lanzavecchia verfasserin aut Elisabetta Cameroni verfasserin aut Elisabetta Cameroni verfasserin aut Davide Corti verfasserin aut Davide Corti verfasserin aut Sarah J. Ratcliffe verfasserin aut Kenneth A. Rogers verfasserin aut Kenneth A. Rogers verfasserin aut Peng Xiao verfasserin aut Jane Fontenot verfasserin aut François Villinger verfasserin aut François Villinger verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.705592 kostenfrei https://doaj.org/article/46765fdad160479eb7819948e8f76c25 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.705592/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021
allfieldsSound	10.3389/fimmu.2021.705592 doi (DE-627)DOAJ057706441 (DE-599)DOAJ46765fdad160479eb7819948e8f76c25 DE-627 ger DE-627 rakwb eng RC581-607 Siqi Gong verfasserin aut Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition. dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion Immunologic diseases. Allergy Siqi Gong verfasserin aut Samir K. Lakhashe verfasserin aut Dinesh Hariraju verfasserin aut Dinesh Hariraju verfasserin aut Hanna Scinto verfasserin aut Hanna Scinto verfasserin aut Antonio Lanzavecchia verfasserin aut Antonio Lanzavecchia verfasserin aut Elisabetta Cameroni verfasserin aut Elisabetta Cameroni verfasserin aut Davide Corti verfasserin aut Davide Corti verfasserin aut Sarah J. Ratcliffe verfasserin aut Kenneth A. Rogers verfasserin aut Kenneth A. Rogers verfasserin aut Peng Xiao verfasserin aut Jane Fontenot verfasserin aut François Villinger verfasserin aut François Villinger verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut Ruth M. Ruprecht verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 12(2021) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:12 year:2021 https://doi.org/10.3389/fimmu.2021.705592 kostenfrei https://doaj.org/article/46765fdad160479eb7819948e8f76c25 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2021.705592/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2021
language	English
source	In Frontiers in Immunology 12(2021) volume:12 year:2021
sourceStr	In Frontiers in Immunology 12(2021) volume:12 year:2021
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion Immunologic diseases. Allergy
isfreeaccess_bool	true
container_title	Frontiers in Immunology
authorswithroles_txt_mv	Siqi Gong @@aut@@ Samir K. Lakhashe @@aut@@ Dinesh Hariraju @@aut@@ Hanna Scinto @@aut@@ Antonio Lanzavecchia @@aut@@ Elisabetta Cameroni @@aut@@ Davide Corti @@aut@@ Sarah J. Ratcliffe @@aut@@ Kenneth A. Rogers @@aut@@ Peng Xiao @@aut@@ Jane Fontenot @@aut@@ François Villinger @@aut@@ Ruth M. Ruprecht @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	657998354
id	DOAJ057706441
language_de	englisch
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callnumber-first	R - Medicine
author	Siqi Gong
spellingShingle	Siqi Gong misc RC581-607 misc dimeric IgA misc IgG misc passive mucosal and systemic immunization misc rhesus macaque model misc SHIV misc immune exclusion misc Immunologic diseases. Allergy Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges
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topic_title	RC581-607 Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges dimeric IgA IgG passive mucosal and systemic immunization rhesus macaque model SHIV immune exclusion
topic	misc RC581-607 misc dimeric IgA misc IgG misc passive mucosal and systemic immunization misc rhesus macaque model misc SHIV misc immune exclusion misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc dimeric IgA misc IgG misc passive mucosal and systemic immunization misc rhesus macaque model misc SHIV misc immune exclusion misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc dimeric IgA misc IgG misc passive mucosal and systemic immunization misc rhesus macaque model misc SHIV misc immune exclusion misc Immunologic diseases. Allergy
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title	Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges
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title_full	Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges
author_sort	Siqi Gong
journal	Frontiers in Immunology
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author_browse	Siqi Gong Samir K. Lakhashe Dinesh Hariraju Hanna Scinto Antonio Lanzavecchia Elisabetta Cameroni Davide Corti Sarah J. Ratcliffe Kenneth A. Rogers Peng Xiao Jane Fontenot François Villinger Ruth M. Ruprecht
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author-letter	Siqi Gong
doi_str_mv	10.3389/fimmu.2021.705592
author2-role	verfasserin
title_sort	cooperation between systemic igg1 and mucosal dimeric iga2 monoclonal anti-hiv env antibodies: passive immunization protects indian rhesus macaques against mucosal shiv challenges
callnumber	RC581-607
title_auth	Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges
abstract	Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition.
abstractGer	Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition.
abstract_unstemmed	Understanding the interplay between systemic and mucosal anti-HIV antibodies can provide important insights to develop new prevention strategies. We used passive immunization via systemic and/or mucosal routes to establish cause-and-effect between well-characterized monoclonal antibodies and protection against intrarectal (i.r.) SHIV challenge. In a pilot study, for which we re-used animals previously exposed to SHIV but completely protected from viremia by different classes of anti-HIV neutralizing monoclonal antibodies (mAbs), we made a surprise finding: low-dose intravenous (i.v.) HGN194-IgG1, a human neutralizing mAb against the conserved V3-loop crown, was ineffective when given alone but protected 100% of animals when combined with i.r. applied HGN194-dIgA2 that by itself had only protected 17% of the animals. Here we sought to confirm the unexpected synergy between systemically administered IgG1 and mucosally applied dIgA HGN194 forms using six groups of naïve macaques (n=6/group). Animals received i.v. HGN194-IgG1 alone or combined with i.r.-administered dIgA forms; controls remained untreated. HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. We conclude that combining suboptimal antibody defenses at systemic and mucosal levels can yield synergy and completely prevent virus acquisition.
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title_short	Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges
url	https://doi.org/10.3389/fimmu.2021.705592 https://doaj.org/article/46765fdad160479eb7819948e8f76c25 https://www.frontiersin.org/articles/10.3389/fimmu.2021.705592/full https://doaj.org/toc/1664-3224
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author2Str	Siqi Gong Samir K. Lakhashe Dinesh Hariraju Hanna Scinto Antonio Lanzavecchia Elisabetta Cameroni Davide Corti Sarah J. Ratcliffe Kenneth A. Rogers Peng Xiao Jane Fontenot François Villinger Ruth M. Ruprecht
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doi_str	10.3389/fimmu.2021.705592
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up_date	2024-07-03T13:37:41.002Z
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HGN194-IgG1 i.v. doses were given 24 hours before – and all i.r. dIgA doses 30 min before – i.r. exposure to a single high-dose of SHIV-1157ipEL-p. All controls became viremic. Among passively immunized animals, the combination of IgG1+dIgA2 again protected 100% of the animals. In contrast, single-agent i.v. IgG1 protected only one of six animals (17%) – consistent with our pilot data. IgG1 combined with dIgA1 or dIgA1+dIgA2 protected 83% (5/6) of the animals. The dIgA1+dIgA2 combination without the systemically administered dose of IgG1 protected 67% (4/6) of the macaques. 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Allergy</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Siqi Gong</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Samir K. Lakhashe</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dinesh Hariraju</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dinesh Hariraju</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hanna Scinto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Hanna Scinto</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Antonio Lanzavecchia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Antonio Lanzavecchia</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Elisabetta Cameroni</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Elisabetta Cameroni</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Davide Corti</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Davide Corti</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Sarah J. 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Cooperation Between Systemic IgG1 and Mucosal Dimeric IgA2 Monoclonal Anti-HIV Env Antibodies: Passive Immunization Protects Indian Rhesus Macaques Against Mucosal SHIV Challenges

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