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J Virol, February 1998, p. 1497-1503, Vol. 72, No. 2
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Increased Immune Response Elicited by DNA Vaccination with a Synthetic gp120 Sequence with Optimized Codon Usage

Stefanie André,1 Brian Seed,2 Josef Eberle,1 Winfried Schraut,3 Andreas Bültmann,1 and Jürgen Haas1,*

Max-von-Pettenkofer Institut, Genzentrum, Universität München, 81377 Munich,1 and Institut für Immunologie, Universität München, 80336 Munich,3 Germany, and Department of Molecular Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 021142

Received 22 July 1997/Accepted 30 October 1997

DNA vaccination elicits humoral and cellular immune responses and has been shown to confer protection against several viral, bacterial, and parasitic pathogens. Here we report that optimized codon usage of an injected DNA sequence considerably increases both humoral and cellular immune responses. We recently generated a synthetic human immunodeficiency virus type 1 gp120 sequence in which most wild-type codons were replaced with codons from highly expressed human genes (syngp120). In vitro expression of syngp120 is considerably increased in comparison to that of the respective wild-type sequence. In BALB/c mice, DNA immunization with syngp120 resulted in significantly increased antibody titers and cytotoxic T-lymphocyte reactivity, suggesting a direct correlation between expression levels and the immune response. Moreover, syngp120 is characterized by rev-independent expression and a low risk of recombination with viral sequences. Thus, synthetic genes with optimized codon usage represent a novel strategy to increase the efficacy and safety of DNA vaccination.

* Corresponding author. Mailing address: Max-von-Pettenkofer Institut, Genzentrum, Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany. Phone: 49 89 74017 201. Fax: 49 89 74017 250. E-mail: haas{at}lmb.uni-muenchen.de.




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