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

被引：11

作者：

Borggren, Marie ^{[1
]}

Vinner, Lasse ^{[1
]}

Andresen, Betina Skovgaard ^{[1
]}

Grevstad, Berit ^{[1
]}

Repits, Johanna ^{[1
]}

Melchers, Mark ^{[2
]}

Elvang, Tara Laura ^{[1
]}

Sanders, Rogier W. ^{[2
]}

Martinon, Frederic ^{[3
]}

Dereuddre-Bosquet, Nathalie ^{[3
]}

Bowles, Emma Joanne ^{[4
]}

Stewart-Jones, Guillaume ^{[4
]}

Biswas, Priscilla ^{[5
]}

Scarlatti, Gabriella ^{[5
]}

Jansson, Marianne ^{[6
]}

Heyndrickx, Leo ^{[7
]}

Le Grand, Roger ^{[3
]}

Fomsgaard, Anders ^{[1
,8
]}

机构：

[1] Statens Serum Inst, Dept Microbiol Diagnost & Virol, DK-2300 Copenhagen, Denmark

[2] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

[3] CEA, Inst Emerging Dis & Immuno Therapies, Div Immuno Virol, F-92260 Fontenay Aux Roses, France

[4] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Human Immunol Unit, Oxford OX3 9DS, England

[5] Ist Sci San Raffaele, I-20123 Milan, Italy

[6] Lund Univ, Dept Lab Med, S-22184 Lund, Sweden

[7] Inst Trop Med, Biomed Dept, Virol Unit, B-2000 Antwerp, Belgium

[8] Univ Soouthern Denmark, Clin Inst, Infect Dis Res Unit, DK-5230 Odense, Denmark

来源：

VACCINES | 2013年 / 1卷 / 03期

关键词：

DNA vaccine; HIV-1; animal models; envelope; neutralizing antibodies;

D O I：

10.3390/vaccines1030305

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：305 / 327

页数：23

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