Abstract
Several gene-based vaccine approaches are being tested to drive multivalent cellular immune responses to control HIV-1 viral variants. To compare the utility of these approaches, HLA-A*0201 transgenic mice were genetically immunized with plasmids encoding wild-type (wt) gag-pol, codon-optimized (CO) gag-pol, and an expression library immunization (ELI) vaccine genetically re-engineered to express non-CO fragments of gag and pol fused to ubiquitin for proteasome targeting. Equimolar delivery of each vaccine into HLA-A*0201 transgenic mice generated CD8 T cell responses, with the ELI vaccine producing up to 10-fold higher responses than the wt or CO gag-pol plasmids against cognate and mutant epitopes. All three vaccines generated multivalent CD8 responses against varying numbers of epitopes after priming. However, when the animals were immunized again, the wt and CO gag-pol vaccines boosted only the responses against a subset of epitopes and attenuated the responses against all other Ags including epitopes from clade and drug-resistant viral variants. In contrast, the ELI vaccine boosted CD8 responses against all of the gag-pol Ags and against mutant epitopes from clade and drug-resistant variants. These data suggest that HIV-1 ...Continue Reading
References
Apr 1, 1991·The Journal of Experimental Medicine·A VitielloR W Chesnut
Aug 1, 1995·Antimicrobial Agents and Chemotherapy·M TisdaleE D Blair
Oct 19, 1995·Nature·M A BarryS A Johnston
Jul 1, 1996·Nature Medicine·A MollaD J Kempf
Dec 13, 1996·The Journal of Biological Chemistry·H B SchockL C Kuo
Mar 3, 1997·The Journal of Experimental Medicine·T W Tobery, R F Siliciano
Jan 5, 1999·Haemophilia : the Official Journal of the World Federation of Hemophilia·J H Condra
Feb 6, 1999·The Journal of General Virology·D RodríguezG del Real
Aug 5, 1999·DNA and Cell Biology·K F Sykes, S A Johnston
Oct 20, 2000·Science·D H BarouchN L Letvin
Feb 13, 2001·Journal of Virology·D H BarouchN L Letvin
Dec 26, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rana A K SinghMichael A Barry
Jan 18, 2002·Nature·John W ShiverEmilio A Emini
Jan 18, 2002·Nature·Dan H BarouchNorman L Letvin
May 22, 2002·Journal of Virology·Sampa SantraNorman L Letvin
May 14, 2003·Journal of Virology·Danilo R CasimiroJohn W Shiver
Citations
Feb 11, 2012·Clinical and Vaccine Immunology : CVI·Steven M SzczepanekLawrence K Silbart
Aug 16, 2019·Journal of Virology·Neil AlmondSteven Patterson
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Geraldine ArrodeOpendra Narayan
Jul 16, 2005·Expert Opinion on Biological Therapy·Steve Pascolo
Jan 31, 2008·PloS One·Irina TcherepanovaCharles A Nicolette
Jan 28, 2006·AIDS Research and Human Retroviruses·Kelly R Young, Ted M Ross
Apr 18, 2014·Journal of Virology·Mauricio A MartinsDavid I Watkins
Nov 3, 2012·PloS One·Adel BenlahrechSteven Patterson
Oct 22, 2005·Infection and Immunity·Adel M Talaat, Katherine Stemke-Hale
Feb 7, 2008·Expert Review of Vaccines·Andreas Boberg, Maria Isaguliants
Jun 5, 2018·PloS One·Stefan PetkovMaria Isaguliants
Sep 27, 2005·Vaccine·Elizaveta StarodubovaMaria Isaguliants