Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose

Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, het...
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Autor*in:	Sholukh, Anton M [verfasserIn] Byrareddy, Siddappa N Shanmuganathan, Vivekanandan Hemashettar, Girish Lakhashe, Samir K Rasmussen, Robert A Watkins, Jennifer D Vyas, Hemant K Thorat, Swati Brandstoetter, Tania Mukhtar, Muhammad M Yoon, John K Novembre, Francis J Villinger, Francois Landucci, Gary Forthal, Donald N Ratcliffe, Sarah Tuero, Iskra Robert-Guroff, Marjorie Polonis, Victoria R Bilska, Miroslawa Montefiori, David C Johnson, Welkin E Ertl, Hildegund C Ruprecht, Ruth M

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2014

Schlagwörter:	Macaque model Heterologous R5 SHIV clade C challenge SHIVIG Passive immunization Enhancement of infection Non-human primate model

Anmerkung:	© Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Retrovirology - London : BioMed Central, 2004, 11(2014), 1 vom: 20. Jan.
Übergeordnetes Werk:	volume:11 ; year:2014 ; number:1 ; day:20 ; month:01

Links:	Volltext

DOI / URN:	10.1186/1742-4690-11-8

Katalog-ID:	SPR029172713

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100	1		\|a Sholukh, Anton M \|e verfasserin \|4 aut
245	1	0	\|a Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose
264		1	\|c 2014
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520			\|a Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter.
650		4	\|a Macaque model \|7 (dpeaa)DE-He213
650		4	\|a Heterologous R5 SHIV clade C challenge \|7 (dpeaa)DE-He213
650		4	\|a SHIVIG \|7 (dpeaa)DE-He213
650		4	\|a Passive immunization \|7 (dpeaa)DE-He213
650		4	\|a Enhancement of infection \|7 (dpeaa)DE-He213
650		4	\|a Non-human primate model \|7 (dpeaa)DE-He213
700	1		\|a Byrareddy, Siddappa N \|4 aut
700	1		\|a Shanmuganathan, Vivekanandan \|4 aut
700	1		\|a Hemashettar, Girish \|4 aut
700	1		\|a Lakhashe, Samir K \|4 aut
700	1		\|a Rasmussen, Robert A \|4 aut
700	1		\|a Watkins, Jennifer D \|4 aut
700	1		\|a Vyas, Hemant K \|4 aut
700	1		\|a Thorat, Swati \|4 aut
700	1		\|a Brandstoetter, Tania \|4 aut
700	1		\|a Mukhtar, Muhammad M \|4 aut
700	1		\|a Yoon, John K \|4 aut
700	1		\|a Novembre, Francis J \|4 aut
700	1		\|a Villinger, Francois \|4 aut
700	1		\|a Landucci, Gary \|4 aut
700	1		\|a Forthal, Donald N \|4 aut
700	1		\|a Ratcliffe, Sarah \|4 aut
700	1		\|a Tuero, Iskra \|4 aut
700	1		\|a Robert-Guroff, Marjorie \|4 aut
700	1		\|a Polonis, Victoria R \|4 aut
700	1		\|a Bilska, Miroslawa \|4 aut
700	1		\|a Montefiori, David C \|4 aut
700	1		\|a Johnson, Welkin E \|4 aut
700	1		\|a Ertl, Hildegund C \|4 aut
700	1		\|a Ruprecht, Ruth M \|4 aut
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912			\|a GBV_ILN_20
912			\|a GBV_ILN_22
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912			\|a GBV_ILN_31
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912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2006
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
912			\|a GBV_ILN_2020
912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2031
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2057
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_4012
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
951			\|a AR
952			\|d 11 \|j 2014 \|e 1 \|b 20 \|c 01

Indexfelder

author_variant	a m s am ams s n b sn snb v s vs g h gh s k l sk skl r a r ra rar j d w jd jdw h k v hk hkv s t st t b tb m m m mm mmm j k y jk jky f j n fj fjn f v fv g l gl d n f dn dnf s r sr i t it m r g mrg v r p vr vrp m b mb d c m dc dcm w e j we wej h c e hc hce r m r rm rmr
matchkey_str	article:17424690:2014----::asvimnztoomcqewtplcoaatsiiggisaeeooosir
hierarchy_sort_str	2014
publishDate	2014
allfields	10.1186/1742-4690-11-8 doi (DE-627)SPR029172713 (SPR)1742-4690-11-8-e DE-627 ger DE-627 rakwb eng Sholukh, Anton M verfasserin aut Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. Macaque model (dpeaa)DE-He213 Heterologous R5 SHIV clade C challenge (dpeaa)DE-He213 SHIVIG (dpeaa)DE-He213 Passive immunization (dpeaa)DE-He213 Enhancement of infection (dpeaa)DE-He213 Non-human primate model (dpeaa)DE-He213 Byrareddy, Siddappa N aut Shanmuganathan, Vivekanandan aut Hemashettar, Girish aut Lakhashe, Samir K aut Rasmussen, Robert A aut Watkins, Jennifer D aut Vyas, Hemant K aut Thorat, Swati aut Brandstoetter, Tania aut Mukhtar, Muhammad M aut Yoon, John K aut Novembre, Francis J aut Villinger, Francois aut Landucci, Gary aut Forthal, Donald N aut Ratcliffe, Sarah aut Tuero, Iskra aut Robert-Guroff, Marjorie aut Polonis, Victoria R aut Bilska, Miroslawa aut Montefiori, David C aut Johnson, Welkin E aut Ertl, Hildegund C aut Ruprecht, Ruth M aut Enthalten in Retrovirology London : BioMed Central, 2004 11(2014), 1 vom: 20. Jan. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:11 year:2014 number:1 day:20 month:01 https://dx.doi.org/10.1186/1742-4690-11-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 11 2014 1 20 01
spelling	10.1186/1742-4690-11-8 doi (DE-627)SPR029172713 (SPR)1742-4690-11-8-e DE-627 ger DE-627 rakwb eng Sholukh, Anton M verfasserin aut Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. Macaque model (dpeaa)DE-He213 Heterologous R5 SHIV clade C challenge (dpeaa)DE-He213 SHIVIG (dpeaa)DE-He213 Passive immunization (dpeaa)DE-He213 Enhancement of infection (dpeaa)DE-He213 Non-human primate model (dpeaa)DE-He213 Byrareddy, Siddappa N aut Shanmuganathan, Vivekanandan aut Hemashettar, Girish aut Lakhashe, Samir K aut Rasmussen, Robert A aut Watkins, Jennifer D aut Vyas, Hemant K aut Thorat, Swati aut Brandstoetter, Tania aut Mukhtar, Muhammad M aut Yoon, John K aut Novembre, Francis J aut Villinger, Francois aut Landucci, Gary aut Forthal, Donald N aut Ratcliffe, Sarah aut Tuero, Iskra aut Robert-Guroff, Marjorie aut Polonis, Victoria R aut Bilska, Miroslawa aut Montefiori, David C aut Johnson, Welkin E aut Ertl, Hildegund C aut Ruprecht, Ruth M aut Enthalten in Retrovirology London : BioMed Central, 2004 11(2014), 1 vom: 20. Jan. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:11 year:2014 number:1 day:20 month:01 https://dx.doi.org/10.1186/1742-4690-11-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 11 2014 1 20 01
allfields_unstemmed	10.1186/1742-4690-11-8 doi (DE-627)SPR029172713 (SPR)1742-4690-11-8-e DE-627 ger DE-627 rakwb eng Sholukh, Anton M verfasserin aut Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. Macaque model (dpeaa)DE-He213 Heterologous R5 SHIV clade C challenge (dpeaa)DE-He213 SHIVIG (dpeaa)DE-He213 Passive immunization (dpeaa)DE-He213 Enhancement of infection (dpeaa)DE-He213 Non-human primate model (dpeaa)DE-He213 Byrareddy, Siddappa N aut Shanmuganathan, Vivekanandan aut Hemashettar, Girish aut Lakhashe, Samir K aut Rasmussen, Robert A aut Watkins, Jennifer D aut Vyas, Hemant K aut Thorat, Swati aut Brandstoetter, Tania aut Mukhtar, Muhammad M aut Yoon, John K aut Novembre, Francis J aut Villinger, Francois aut Landucci, Gary aut Forthal, Donald N aut Ratcliffe, Sarah aut Tuero, Iskra aut Robert-Guroff, Marjorie aut Polonis, Victoria R aut Bilska, Miroslawa aut Montefiori, David C aut Johnson, Welkin E aut Ertl, Hildegund C aut Ruprecht, Ruth M aut Enthalten in Retrovirology London : BioMed Central, 2004 11(2014), 1 vom: 20. Jan. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:11 year:2014 number:1 day:20 month:01 https://dx.doi.org/10.1186/1742-4690-11-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 11 2014 1 20 01
allfieldsGer	10.1186/1742-4690-11-8 doi (DE-627)SPR029172713 (SPR)1742-4690-11-8-e DE-627 ger DE-627 rakwb eng Sholukh, Anton M verfasserin aut Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. Macaque model (dpeaa)DE-He213 Heterologous R5 SHIV clade C challenge (dpeaa)DE-He213 SHIVIG (dpeaa)DE-He213 Passive immunization (dpeaa)DE-He213 Enhancement of infection (dpeaa)DE-He213 Non-human primate model (dpeaa)DE-He213 Byrareddy, Siddappa N aut Shanmuganathan, Vivekanandan aut Hemashettar, Girish aut Lakhashe, Samir K aut Rasmussen, Robert A aut Watkins, Jennifer D aut Vyas, Hemant K aut Thorat, Swati aut Brandstoetter, Tania aut Mukhtar, Muhammad M aut Yoon, John K aut Novembre, Francis J aut Villinger, Francois aut Landucci, Gary aut Forthal, Donald N aut Ratcliffe, Sarah aut Tuero, Iskra aut Robert-Guroff, Marjorie aut Polonis, Victoria R aut Bilska, Miroslawa aut Montefiori, David C aut Johnson, Welkin E aut Ertl, Hildegund C aut Ruprecht, Ruth M aut Enthalten in Retrovirology London : BioMed Central, 2004 11(2014), 1 vom: 20. Jan. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:11 year:2014 number:1 day:20 month:01 https://dx.doi.org/10.1186/1742-4690-11-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 11 2014 1 20 01
allfieldsSound	10.1186/1742-4690-11-8 doi (DE-627)SPR029172713 (SPR)1742-4690-11-8-e DE-627 ger DE-627 rakwb eng Sholukh, Anton M verfasserin aut Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. Macaque model (dpeaa)DE-He213 Heterologous R5 SHIV clade C challenge (dpeaa)DE-He213 SHIVIG (dpeaa)DE-He213 Passive immunization (dpeaa)DE-He213 Enhancement of infection (dpeaa)DE-He213 Non-human primate model (dpeaa)DE-He213 Byrareddy, Siddappa N aut Shanmuganathan, Vivekanandan aut Hemashettar, Girish aut Lakhashe, Samir K aut Rasmussen, Robert A aut Watkins, Jennifer D aut Vyas, Hemant K aut Thorat, Swati aut Brandstoetter, Tania aut Mukhtar, Muhammad M aut Yoon, John K aut Novembre, Francis J aut Villinger, Francois aut Landucci, Gary aut Forthal, Donald N aut Ratcliffe, Sarah aut Tuero, Iskra aut Robert-Guroff, Marjorie aut Polonis, Victoria R aut Bilska, Miroslawa aut Montefiori, David C aut Johnson, Welkin E aut Ertl, Hildegund C aut Ruprecht, Ruth M aut Enthalten in Retrovirology London : BioMed Central, 2004 11(2014), 1 vom: 20. Jan. (DE-627)385612931 (DE-600)2142602-8 1742-4690 nnns volume:11 year:2014 number:1 day:20 month:01 https://dx.doi.org/10.1186/1742-4690-11-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 11 2014 1 20 01
language	English
source	Enthalten in Retrovirology 11(2014), 1 vom: 20. Jan. volume:11 year:2014 number:1 day:20 month:01
sourceStr	Enthalten in Retrovirology 11(2014), 1 vom: 20. Jan. volume:11 year:2014 number:1 day:20 month:01
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Macaque model Heterologous R5 SHIV clade C challenge SHIVIG Passive immunization Enhancement of infection Non-human primate model
isfreeaccess_bool	true
container_title	Retrovirology
authorswithroles_txt_mv	Sholukh, Anton M @@aut@@ Byrareddy, Siddappa N @@aut@@ Shanmuganathan, Vivekanandan @@aut@@ Hemashettar, Girish @@aut@@ Lakhashe, Samir K @@aut@@ Rasmussen, Robert A @@aut@@ Watkins, Jennifer D @@aut@@ Vyas, Hemant K @@aut@@ Thorat, Swati @@aut@@ Brandstoetter, Tania @@aut@@ Mukhtar, Muhammad M @@aut@@ Yoon, John K @@aut@@ Novembre, Francis J @@aut@@ Villinger, Francois @@aut@@ Landucci, Gary @@aut@@ Forthal, Donald N @@aut@@ Ratcliffe, Sarah @@aut@@ Tuero, Iskra @@aut@@ Robert-Guroff, Marjorie @@aut@@ Polonis, Victoria R @@aut@@ Bilska, Miroslawa @@aut@@ Montefiori, David C @@aut@@ Johnson, Welkin E @@aut@@ Ertl, Hildegund C @@aut@@ Ruprecht, Ruth M @@aut@@
publishDateDaySort_date	2014-01-20T00:00:00Z
hierarchy_top_id	385612931
id	SPR029172713
language_de	englisch
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. 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author	Sholukh, Anton M
spellingShingle	Sholukh, Anton M misc Macaque model misc Heterologous R5 SHIV clade C challenge misc SHIVIG misc Passive immunization misc Enhancement of infection misc Non-human primate model Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose
authorStr	Sholukh, Anton M
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topic_title	Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose Macaque model (dpeaa)DE-He213 Heterologous R5 SHIV clade C challenge (dpeaa)DE-He213 SHIVIG (dpeaa)DE-He213 Passive immunization (dpeaa)DE-He213 Enhancement of infection (dpeaa)DE-He213 Non-human primate model (dpeaa)DE-He213
topic	misc Macaque model misc Heterologous R5 SHIV clade C challenge misc SHIVIG misc Passive immunization misc Enhancement of infection misc Non-human primate model
topic_unstemmed	misc Macaque model misc Heterologous R5 SHIV clade C challenge misc SHIVIG misc Passive immunization misc Enhancement of infection misc Non-human primate model
topic_browse	misc Macaque model misc Heterologous R5 SHIV clade C challenge misc SHIVIG misc Passive immunization misc Enhancement of infection misc Non-human primate model
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title	Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose
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title_full	Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose
author_sort	Sholukh, Anton M
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author_browse	Sholukh, Anton M Byrareddy, Siddappa N Shanmuganathan, Vivekanandan Hemashettar, Girish Lakhashe, Samir K Rasmussen, Robert A Watkins, Jennifer D Vyas, Hemant K Thorat, Swati Brandstoetter, Tania Mukhtar, Muhammad M Yoon, John K Novembre, Francis J Villinger, Francois Landucci, Gary Forthal, Donald N Ratcliffe, Sarah Tuero, Iskra Robert-Guroff, Marjorie Polonis, Victoria R Bilska, Miroslawa Montefiori, David C Johnson, Welkin E Ertl, Hildegund C Ruprecht, Ruth M
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doi_str_mv	10.1186/1742-4690-11-8
title_sort	passive immunization of macaques with polyclonal anti-shiv igg against a heterologous tier 2 shiv: outcome depends on igg dose
title_auth	Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose
abstract	Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. Conclusion Our primate model data suggest a dual role for polyclonal anti-HIV-1 Abs depending on plasma levels upon virus encounter. © Sholukh et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
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title_short	Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose
url	https://dx.doi.org/10.1186/1742-4690-11-8
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author2	Byrareddy, Siddappa N Shanmuganathan, Vivekanandan Hemashettar, Girish Lakhashe, Samir K Rasmussen, Robert A Watkins, Jennifer D Vyas, Hemant K Thorat, Swati Brandstoetter, Tania Mukhtar, Muhammad M Yoon, John K Novembre, Francis J Villinger, Francois Landucci, Gary Forthal, Donald N Ratcliffe, Sarah Tuero, Iskra Robert-Guroff, Marjorie Polonis, Victoria R Bilska, Miroslawa Montefiori, David C Johnson, Welkin E Ertl, Hildegund C Ruprecht, Ruth M
author2Str	Byrareddy, Siddappa N Shanmuganathan, Vivekanandan Hemashettar, Girish Lakhashe, Samir K Rasmussen, Robert A Watkins, Jennifer D Vyas, Hemant K Thorat, Swati Brandstoetter, Tania Mukhtar, Muhammad M Yoon, John K Novembre, Francis J Villinger, Francois Landucci, Gary Forthal, Donald N Ratcliffe, Sarah Tuero, Iskra Robert-Guroff, Marjorie Polonis, Victoria R Bilska, Miroslawa Montefiori, David C Johnson, Welkin E Ertl, Hildegund C Ruprecht, Ruth M
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doi_str	10.1186/1742-4690-11-8
up_date	2024-07-03T23:48:19.662Z
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background A key goal for HIV-1 envelope immunogen design is the induction of cross-reactive neutralizing antibodies (nAbs). As AIDS vaccine recipients will not be exposed to strains exactly matching any immunogens due to multiple HIV-1 quasispecies circulating in the human population worldwide, heterologous SHIV challenges are essential for realistic vaccine efficacy testing in primates. We assessed whether polyclonal IgG, isolated from rhesus monkeys (RMs) with high-titer nAbs (termed SHIVIG), could protect RMs against the R5-tropic tier-2 SHIV-2873Nip, which was heterologous to the viruses or HIV-1 envelopes that had elicited SHIVIG. Results SHIVIG demonstrated binding to HIV Gag, Tat, and Env of different clades and competed with the broadly neutralizing antibodies b12, VRC01, 4E10, and 17b. SHIVIG neutralized tier 1 and tier 2 viruses, including SHIV-2873Nip. NK-cell depletion decreased the neutralizing activity of SHIVIG 20-fold in PBMC assays. Although SHIVIG neutralized SHIV-2873Nip in vitro, this polyclonal IgG preparation failed to prevent acquisition after repeated intrarectal low-dose virus challenges, but at a dose of 400 mg/kg, it significantly lowered peak viremia (P = 0.001). Unexpectedly, single-genome analysis revealed a higher number of transmitted variants at the low dose of 25 mg/kg, implying increased acquisition at low SHIVIG levels. In vitro, SHIVIG demonstrated complement-mediated Ab-dependent enhancement of infection (C’-ADE) at concentrations similar to those observed in plasmas of RMs treated with 25 mg/kg of SHIVIG. 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Passive immunization of macaques with polyclonal anti-SHIV IgG against a heterologous tier 2 SHIV: outcome depends on IgG dose

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