title: A recoding method to improve the humoral immune response to an HIV DNA vaccine.
abstract: This manuscript describes a novel strategy to improve HIV DNA vaccine design. Employing a new information theory based bioinformatic algorithm, we identify a set of nucleotide motifs which are common in the coding region of HIV, but are under-represented in genes that are highly expressed in the human genome. We hypothesize that these motifs contribute to the poor protein expression of gag, pol, and env genes from the c-DNAs of HIV clinical isolates. Using this approach and beginning with a codon optimized consensus gag gene, we recode the nucleotide sequence so as to remove these motifs without modifying the amino acid sequence. Transfecting the recoded DNA sequence into a human kidney cell line results in doubling the gag protein expression level compared to the codon optimized version. We then turn both sequences into DNA vaccines and compare induced antibody response in a murine model. Our sequence, which has the motifs removed, induces a five-fold increase in gag antibody response compared to the codon optimized vaccine.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York, United States of America.
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Krasnitz
authors.forename: Raul
authors.initials: R
authors.lastname: Rabadan
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Witten
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Levine
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Harlan
authors.initials: H
authors.lastname: Robins
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D000465:Algorithms; D020816:Amino Acid Motifs; D000818:Animals; D000917:Antibody Formation / Q000235:genetics*; D003062:Codon; D019295:Computational Biology / Q000379:methods; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D015683:Gene Products, gag / Q000378:metabolism; D006801:Humans; D051379:Mice; D009010:Monte Carlo Method
chemical_list: D016915:AIDS Vaccines; D003062:Codon; D018076:DNA, Complementary; D015683:Gene Products, gag
references.citation: J Virol. 2000 May;74(10):4839-52
references.pmid: 10775623
references.citation: Hum Gene Ther. 2006 Nov;17(11):1051-61
references.pmid: 17032152
references.citation: J Bacteriol. 2005 Dec;187(24):8370-4
references.pmid: 16321941
references.citation: Int Rev Immunol. 2006 May-Aug;25(3-4):99-123
references.pmid: 16818367
references.citation: Trends Biochem Sci. 2003 Aug;28(8):419-24
references.pmid: 12932730
references.citation: J Virol. 1997 Jul;71(7):4892-903
references.pmid: 9188551