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

Vaccines

Marie Borggren²  Lasse Vinner²  Betina Skovgaard Andresen²  Berit Grevstad²  Johanna Repits²  Mark Melchers⁴  Tara Laura Elvang²  Rogier W Sanders⁴  Frຝéric Martinon⁶  Nathalie Dereuddre-Bosquet⁶  Emma Joanne Bowles⁷  Guillaume Stewart-Jones⁷  Priscilla Biswas³  Gabriella Scarlatti³  Marianne Jansson¹  Leo Heyndrickx⁵  Roger Le Grand⁶ 

[1] Department of Laboratory Medicine, Lund University, Lund 22184, Sweden;Department of Microbiology Diagnostics and Virology, Statens Serum Institut, Copenhagen 2300, Denmark;San Raffaele Scientific Institute, Milan 20123, Italy;Department of Medical Microbiology, Academic Medical Center of the University of Amsterdam, Amsterdam 1105, The Netherlands;Biomedical Department, Virology Unit, Institute of Tropical Medicine, Antwerp 2000, Belgium;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

关键词: DNA vaccine;    HIV-1;    animal models;    envelope;    neutralizing antibodies;   

DOI  :  10.3390/vaccines1030305

来源: mdpi

【 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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.