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

Vaccines
Marie BorggrenAnders Fomsgaard

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 bes...Continue Reading

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Citations

May 16, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hannes UchtenhagenAnna-Lena Spetz
Nov 14, 2014·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Sanne S JensenIngrid Karlsson
Feb 12, 2021·Viruses·Anders Fomsgaard, Margaret A Liu

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Datasets Mentioned

BETA
JX473289

Methods Mentioned

BETA
transfection
gel filtration
ELISA
FCS

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