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Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques
Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark
Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam 1105, The Netherlands
Division of Immuno-Virology, Institute of Emerging Diseases and Immuno Therapies, CEA, Fontenay aux Roses 92260, France
Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK
San Raffaele Scientific Institute, Milan 20123, Italy
Department of Laboratory Medicine, Lund University, Lund 22184, Sweden
Biomedical Department, Virology Unit, Institute of Tropical Medicine, Antwerp 2000, Belgium
Infectious Disease Research Unit, Clinical Institute, University of Southern Denmark, Odense 5230, Denmark
Member of the NGIN consortium. Other members of the group are listed in the acknowledgment.
* Author to whom correspondence should be addressed.
Received: 16 May 2013; in revised form: 5 July 2013 / Accepted: 10 July 2013 / Published: 19 July 2013
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.
Keywords: DNA vaccine; HIV-1; animal models; envelope; neutralizing antibodies
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Borggren, M.; Vinner, L.; Andresen, B.S.; Grevstad, B.; Repits, J.; Melchers, M.; Elvang, T.L.; Sanders, R.W.; Martinon, F.; Dereuddre-Bosquet, N.; Bowles, E.J.; Stewart-Jones, G.; Biswas, P.; Scarlatti, G.; Jansson, M.; Heyndrickx, L.; Grand, R.L.; Fomsgaard, A. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques. Vaccines 2013, 1, 305-327.
Borggren M, Vinner L, Andresen BS, Grevstad B, Repits J, Melchers M, Elvang TL, Sanders RW, Martinon F, Dereuddre-Bosquet N, Bowles EJ, Stewart-Jones G, Biswas P, Scarlatti G, Jansson M, Heyndrickx L, Grand RL, Fomsgaard A. Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques. Vaccines. 2013; 1(3):305-327.
Borggren, Marie; Vinner, Lasse; Andresen, Betina S.; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara L.; Sanders, Rogier W.; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma J.; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger L.; Fomsgaard, Anders. 2013. "Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques." Vaccines 1, no. 3: 305-327.