Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antib...
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Autor*in:	Roger Le Grand [verfasserIn] Anders Fomsgaard [verfasserIn] Marianne Jansson [verfasserIn] Leo Heyndrickx [verfasserIn] Gabriella Scarlatti [verfasserIn] Priscilla Biswas [verfasserIn] Guillaume Stewart-Jones [verfasserIn] Emma Joanne Bowles [verfasserIn] Nathalie Dereuddre-Bosquet [verfasserIn] Frédéric Martinon [verfasserIn] Rogier W Sanders [verfasserIn] Mark Melchers [verfasserIn] Tara Laura Elvang [verfasserIn] Betina Skovgaard Andresen [verfasserIn] Berit Grevstad [verfasserIn] Johanna Repits [verfasserIn] Marie Borggren [verfasserIn] Lasse Vinner [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2013

Schlagwörter:	DNA vaccine HIV-1 animal models envelope neutralizing antibodies

Übergeordnetes Werk:	In: Vaccines - MDPI AG, 2013, 1(2013), 3, Seite 305-327
Übergeordnetes Werk:	volume:1 ; year:2013 ; number:3 ; pages:305-327

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/vaccines1030305

Katalog-ID:	DOAJ085054488

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allfields	10.3390/vaccines1030305 doi (DE-627)DOAJ085054488 (DE-599)DOAJa2b7b1bb8b1d446496f7f69f5e152250 DE-627 ger DE-627 rakwb eng Roger Le Grand verfasserin aut Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. DNA vaccine HIV-1 animal models envelope neutralizing antibodies Medicine R Anders Fomsgaard verfasserin aut Marianne Jansson verfasserin aut Leo Heyndrickx verfasserin aut Gabriella Scarlatti verfasserin aut Priscilla Biswas verfasserin aut Guillaume Stewart-Jones verfasserin aut Emma Joanne Bowles verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Frédéric Martinon verfasserin aut Rogier W Sanders verfasserin aut Mark Melchers verfasserin aut Tara Laura Elvang verfasserin aut Betina Skovgaard Andresen verfasserin aut Berit Grevstad verfasserin aut Johanna Repits verfasserin aut Marie Borggren verfasserin aut Lasse Vinner verfasserin aut In Vaccines MDPI AG, 2013 1(2013), 3, Seite 305-327 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:1 year:2013 number:3 pages:305-327 https://doi.org/10.3390/vaccines1030305 kostenfrei https://doaj.org/article/a2b7b1bb8b1d446496f7f69f5e152250 kostenfrei http://www.mdpi.com/2076-393X/1/3/305 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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_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 1 2013 3 305-327
spelling	10.3390/vaccines1030305 doi (DE-627)DOAJ085054488 (DE-599)DOAJa2b7b1bb8b1d446496f7f69f5e152250 DE-627 ger DE-627 rakwb eng Roger Le Grand verfasserin aut Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. DNA vaccine HIV-1 animal models envelope neutralizing antibodies Medicine R Anders Fomsgaard verfasserin aut Marianne Jansson verfasserin aut Leo Heyndrickx verfasserin aut Gabriella Scarlatti verfasserin aut Priscilla Biswas verfasserin aut Guillaume Stewart-Jones verfasserin aut Emma Joanne Bowles verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Frédéric Martinon verfasserin aut Rogier W Sanders verfasserin aut Mark Melchers verfasserin aut Tara Laura Elvang verfasserin aut Betina Skovgaard Andresen verfasserin aut Berit Grevstad verfasserin aut Johanna Repits verfasserin aut Marie Borggren verfasserin aut Lasse Vinner verfasserin aut In Vaccines MDPI AG, 2013 1(2013), 3, Seite 305-327 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:1 year:2013 number:3 pages:305-327 https://doi.org/10.3390/vaccines1030305 kostenfrei https://doaj.org/article/a2b7b1bb8b1d446496f7f69f5e152250 kostenfrei http://www.mdpi.com/2076-393X/1/3/305 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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_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 1 2013 3 305-327
allfields_unstemmed	10.3390/vaccines1030305 doi (DE-627)DOAJ085054488 (DE-599)DOAJa2b7b1bb8b1d446496f7f69f5e152250 DE-627 ger DE-627 rakwb eng Roger Le Grand verfasserin aut Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. DNA vaccine HIV-1 animal models envelope neutralizing antibodies Medicine R Anders Fomsgaard verfasserin aut Marianne Jansson verfasserin aut Leo Heyndrickx verfasserin aut Gabriella Scarlatti verfasserin aut Priscilla Biswas verfasserin aut Guillaume Stewart-Jones verfasserin aut Emma Joanne Bowles verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Frédéric Martinon verfasserin aut Rogier W Sanders verfasserin aut Mark Melchers verfasserin aut Tara Laura Elvang verfasserin aut Betina Skovgaard Andresen verfasserin aut Berit Grevstad verfasserin aut Johanna Repits verfasserin aut Marie Borggren verfasserin aut Lasse Vinner verfasserin aut In Vaccines MDPI AG, 2013 1(2013), 3, Seite 305-327 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:1 year:2013 number:3 pages:305-327 https://doi.org/10.3390/vaccines1030305 kostenfrei https://doaj.org/article/a2b7b1bb8b1d446496f7f69f5e152250 kostenfrei http://www.mdpi.com/2076-393X/1/3/305 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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_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 1 2013 3 305-327
allfieldsGer	10.3390/vaccines1030305 doi (DE-627)DOAJ085054488 (DE-599)DOAJa2b7b1bb8b1d446496f7f69f5e152250 DE-627 ger DE-627 rakwb eng Roger Le Grand verfasserin aut Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. DNA vaccine HIV-1 animal models envelope neutralizing antibodies Medicine R Anders Fomsgaard verfasserin aut Marianne Jansson verfasserin aut Leo Heyndrickx verfasserin aut Gabriella Scarlatti verfasserin aut Priscilla Biswas verfasserin aut Guillaume Stewart-Jones verfasserin aut Emma Joanne Bowles verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Frédéric Martinon verfasserin aut Rogier W Sanders verfasserin aut Mark Melchers verfasserin aut Tara Laura Elvang verfasserin aut Betina Skovgaard Andresen verfasserin aut Berit Grevstad verfasserin aut Johanna Repits verfasserin aut Marie Borggren verfasserin aut Lasse Vinner verfasserin aut In Vaccines MDPI AG, 2013 1(2013), 3, Seite 305-327 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:1 year:2013 number:3 pages:305-327 https://doi.org/10.3390/vaccines1030305 kostenfrei https://doaj.org/article/a2b7b1bb8b1d446496f7f69f5e152250 kostenfrei http://www.mdpi.com/2076-393X/1/3/305 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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_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 1 2013 3 305-327
allfieldsSound	10.3390/vaccines1030305 doi (DE-627)DOAJ085054488 (DE-599)DOAJa2b7b1bb8b1d446496f7f69f5e152250 DE-627 ger DE-627 rakwb eng Roger Le Grand verfasserin aut Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. DNA vaccine HIV-1 animal models envelope neutralizing antibodies Medicine R Anders Fomsgaard verfasserin aut Marianne Jansson verfasserin aut Leo Heyndrickx verfasserin aut Gabriella Scarlatti verfasserin aut Priscilla Biswas verfasserin aut Guillaume Stewart-Jones verfasserin aut Emma Joanne Bowles verfasserin aut Nathalie Dereuddre-Bosquet verfasserin aut Frédéric Martinon verfasserin aut Rogier W Sanders verfasserin aut Mark Melchers verfasserin aut Tara Laura Elvang verfasserin aut Betina Skovgaard Andresen verfasserin aut Berit Grevstad verfasserin aut Johanna Repits verfasserin aut Marie Borggren verfasserin aut Lasse Vinner verfasserin aut In Vaccines MDPI AG, 2013 1(2013), 3, Seite 305-327 (DE-627)736559205 (DE-600)2703319-3 2076393X nnns volume:1 year:2013 number:3 pages:305-327 https://doi.org/10.3390/vaccines1030305 kostenfrei https://doaj.org/article/a2b7b1bb8b1d446496f7f69f5e152250 kostenfrei http://www.mdpi.com/2076-393X/1/3/305 kostenfrei https://doaj.org/toc/2076-393X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_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_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 1 2013 3 305-327
language	English
source	In Vaccines 1(2013), 3, Seite 305-327 volume:1 year:2013 number:3 pages:305-327
sourceStr	In Vaccines 1(2013), 3, Seite 305-327 volume:1 year:2013 number:3 pages:305-327
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	DNA vaccine HIV-1 animal models envelope neutralizing antibodies Medicine R
isfreeaccess_bool	true
container_title	Vaccines
authorswithroles_txt_mv	Roger Le Grand @@aut@@ Anders Fomsgaard @@aut@@ Marianne Jansson @@aut@@ Leo Heyndrickx @@aut@@ Gabriella Scarlatti @@aut@@ Priscilla Biswas @@aut@@ Guillaume Stewart-Jones @@aut@@ Emma Joanne Bowles @@aut@@ Nathalie Dereuddre-Bosquet @@aut@@ Frédéric Martinon @@aut@@ Rogier W Sanders @@aut@@ Mark Melchers @@aut@@ Tara Laura Elvang @@aut@@ Betina Skovgaard Andresen @@aut@@ Berit Grevstad @@aut@@ Johanna Repits @@aut@@ Marie Borggren @@aut@@ Lasse Vinner @@aut@@
publishDateDaySort_date	2013-01-01T00:00:00Z
hierarchy_top_id	736559205
id	DOAJ085054488
language_de	englisch
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author	Roger Le Grand
spellingShingle	Roger Le Grand misc DNA vaccine misc HIV-1 misc animal models misc envelope misc neutralizing antibodies misc Medicine misc R Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques
authorStr	Roger Le Grand
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topic_title	Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques DNA vaccine HIV-1 animal models envelope neutralizing antibodies
topic	misc DNA vaccine misc HIV-1 misc animal models misc envelope misc neutralizing antibodies misc Medicine misc R
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title	Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques
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title_full	Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques
author_sort	Roger Le Grand
journal	Vaccines
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author_browse	Roger Le Grand Anders Fomsgaard Marianne Jansson Leo Heyndrickx Gabriella Scarlatti Priscilla Biswas Guillaume Stewart-Jones Emma Joanne Bowles Nathalie Dereuddre-Bosquet Frédéric Martinon Rogier W Sanders Mark Melchers Tara Laura Elvang Betina Skovgaard Andresen Berit Grevstad Johanna Repits Marie Borggren Lasse Vinner
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title_sort	optimization of hiv-1 envelope dna vaccine candidates within three different animal models, guinea pigs, rabbits and cynomolgus macaques
title_auth	Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques
abstract	HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.
abstractGer	HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.
abstract_unstemmed	HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.
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title_short	Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques
url	https://doi.org/10.3390/vaccines1030305 https://doaj.org/article/a2b7b1bb8b1d446496f7f69f5e152250 http://www.mdpi.com/2076-393X/1/3/305 https://doaj.org/toc/2076-393X
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author2	Anders Fomsgaard Marianne Jansson Leo Heyndrickx Gabriella Scarlatti Priscilla Biswas Guillaume Stewart-Jones Emma Joanne Bowles Nathalie Dereuddre-Bosquet Frédéric Martinon Rogier W Sanders Mark Melchers Tara Laura Elvang Betina Skovgaard Andresen Berit Grevstad Johanna Repits Marie Borggren Lasse Vinner
author2Str	Anders Fomsgaard Marianne Jansson Leo Heyndrickx Gabriella Scarlatti Priscilla Biswas Guillaume Stewart-Jones Emma Joanne Bowles Nathalie Dereuddre-Bosquet Frédéric Martinon Rogier W Sanders Mark Melchers Tara Laura Elvang Betina Skovgaard Andresen Berit Grevstad Johanna Repits Marie Borggren Lasse Vinner
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up_date	2024-07-04T01:39:23.676Z
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