Induction of HIV-1 subtype B and AE-specific neutralizing antibodies in mice and macaques with DNA prime and recombinant gp140 protein boost regimens
Rob J Center, Adam K Wheatley, Shahan M Campbell, Adriana J Gaeguta, Viv Peut, Sheilajen Alcantara, Carly Siebentritt, Stephen J Kent, Damian FJ Purcell
VACCINE | ELSEVIER SCI LTD | Published : 2009
We developed highly expressing clade B and AE DNA and envelope protein (Env) vaccines for evaluation in mice and macaques as DNA prime/protein boost regimens. High levels of Env-specific antibodies were induced in mice, albeit with limited neutralizing activity in vitro. A combined clade B and AE regimen induced high titer Env-specific antibody in two pigtail macaques that neutralized several strains of HIV-1. However, upon mucosal challenge with SHIV(SF162P3) no protection from infection was observed. Although the vaccines tested provide a platform for inducing robust humoral immunity, further refinements to broaden coverage against divergent strains and induce mucosal immunity are needed.
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Awarded by Australian NHMRC
We thank Dr. Robert De Rose, Thakshila Amarasena, Caroline Fernandez, Jeanette Reece, Roberta Goli and Leanne Smith for expert technical assistance. This work was supported financially by the Australian NHMRC (Program Grant 299907 and Career Development Award 359233 to RJC) and the Australian Centre for HIV and Hepatitis Virology Research. The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: pSVIII-93.TH976.17 (for production of pseudovirus) and pCRII-93TH966-89 (the source of the HIV-1<INF>93TH966</INF> env gene and for pseudovirus production) from Dr. Beatrice Hahn and SIV<INF>mac239</INF> Gag and HIV-1<INF>MN</INF> Env peptides. Plasmids pNL(AD8) and pNL4-3 (the source of HIV-1<INF>AD8</INF> and HIV-1<INF>NL4.3</INF> env genes) were provided by Dr. Malcolm Martin. Dr. Leonidas Stamatatos provided pCAGGS SF162 gp160 used for pseudovirus production. Montanide ISA 51 VG (Seppic) was provided by the Tall Bennett Group. We thank Dr. Simon Crawford for assistance with electron microscopy.