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 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.
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark.
Marie
M
Borggren
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark.
Lasse
L
Vinner
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark.
Betina Skovgaard
BS
Andresen
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark.
Berit
B
Grevstad
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark.
Johanna
J
Repits
Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam 1105, The Netherlands.
Mark
M
Melchers
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark.
Tara Laura
TL
Elvang
Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam 1105, The Netherlands.
Rogier W
RW
Sanders
Division of Immuno-Virology, Institute of Emerging Diseases and Immuno Therapies, CEA, Fontenay aux Roses 92260, France.
Frédéric
F
Martinon
Division of Immuno-Virology, Institute of Emerging Diseases and Immuno Therapies, CEA, Fontenay aux Roses 92260, France.
Nathalie
N
Dereuddre-Bosquet
Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Emma Joanne
EJ
Bowles
Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.
Guillaume
G
Stewart-Jones
San Raffaele Scientific Institute, Milan 20123, Italy.
Priscilla
P
Biswas
San Raffaele Scientific Institute, Milan 20123, Italy.
Gabriella
G
Scarlatti
Department of Laboratory Medicine, Lund University, Lund 22184, Sweden.
Marianne
M
Jansson
Biomedical Department, Virology Unit, Institute of Tropical Medicine, Antwerp 2000, Belgium.
Leo
L
Heyndrickx
Division of Immuno-Virology, Institute of Emerging Diseases and Immuno Therapies, CEA, Fontenay aux Roses 92260, France.
Roger Le
RL
Grand
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark. afo@ssi.dk.|Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense 5230, Denmark. afo@ssi.dk.
Anders
A
Fomsgaard
DNA vaccine; HIV-1; animal models; envelope; neutralizing antibodies