New kinds of HIV vaccines are needed to elicit strong immunity, particularly T cell responses. E2DISP, a protein domain from the thermophilic bacterium B. stearothermophilus, self-assembles into 24 nm virus-like particles and can display 60 copies of a foreign antigen on the particle surface. Unlike most other soluble antigens, the E2DISP particle accesses both MHC Class I and Class II pathways, and elicits T cell immunity. T and B cell epitopes of HIV reverse transcriptase made as fusion proteins with E2DISP are effectively presented in vivo and elicited both cytotoxic T cells and antibodies in mice. The overall goal of this proposal is to determine whether whole HIV proteins can be expressed as E2DISP fusion proteins, and whether the resulting particles are immunogenic in mice. We have demonstrated that E2Gag-p17, E2Gag-p24, and E2Gag-p17/24 particles are produced efficiently in this system, and preliminary data suggest that E2Gag-p17 elicits cytotoxic T cells and antibody in mice. We propose to also clone Rev, Tat, Nef, and large regions of Env as E2 fusions, optimize their purification, and assess their antigenicity. Each clone will be used to immunize mice and we will measure CTL activity and antibodies against HIV. We will also assess the possibility of using multiple doses of E2-HIV proteins. Because the E2 complexes can be made in E. coli, and can elicit both cellular and humoral immunity, they have great potential as safe, effective and inexpensive vaccine components.
| Jaworski, Juan Pablo; Krebs, Shelly J; Trovato, Maria et al. (2012) Co-immunization with multimeric scaffolds and DNA rapidly induces potent autologous HIV-1 neutralizing antibodies and CD8+ T cells. PLoS One 7:e31464 |
| Caivano, Antonella; Doria-Rose, Nicole A; Buelow, Benjamin et al. (2010) HIV-1 Gag p17 presented as virus-like particles on the E2 scaffold from Geobacillus stearothermophilus induces sustained humoral and cellular immune responses in the absence of IFN? production by CD4+ T cells. Virology 407:296-305 |
| Blish, Catherine A; Blay, Wendy M; Haigwood, Nancy L et al. (2007) Transmission of HIV-1 in the face of neutralizing antibodies. Curr HIV Res 5:578-87 |
