Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen†0--

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic groupMconsensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from heterologous subtype A, B, and C viruses. The CON6-derived vaccine was immunogenic and induced a greater number of T-cell epitope responses than any single wild-type subtype A, B, and C env immunogen and similar T-cell responses to a polyvalent vaccine. The responses were comparable to within-clade responses but significantly more than between-clade responses. The magnitude of the T-cell responses induced by CON6 (measured by individual epitope peptides) was also greater than the magnitude of responses induced by individual wild-type env immunogens. Though the limited major histocompatibility complex repertoire in inbred mice does not necessarily predict responses in nonhuman primates and humans, these results suggest that synthetic centralized env immunogens represent a promising approach for HIV-1 vaccine design that merits further characterization

Cross-Subtype T-Cell Immune Responses Induced by a Human Immunodeficiency Virus Type 1 Group M Consensus Env Immunogen

The genetic diversity among globally circulating human immunodeficiency virus type 1 (HIV-1) strains is a serious challenge for HIV-1 vaccine design. We have generated a synthetic group M consensus env gene (CON6) for induction of cross-subtype immune responses and report here a comparative study of T-cell responses to this and natural strain env immunogens in a murine model. Three different strains of mice were immunized with CON6 as well as subtype A, B, or C env immunogens, using a DNA prime-recombinant vaccinia virus boost strategy. T-cell epitopes were mapped by gamma interferon enzyme-linked immunospot analysis using five overlapping Env peptide sets from heterologous subtype A, B, and C viruses. The CON6-derived vaccine was immunogenic and induced a greater number of T-cell epitope responses than any single wild-type subtype A, B, and C env immunogen and similar T-cell responses to a polyvalent vaccine. The responses were comparable to within-clade responses but significantly more than between-clade responses. The magnitude of the T-cell responses induced by CON6 (measured by individual epitope peptides) was also greater than the magnitude of responses induced by individual wild-type env immunogens. Though the limited major histocompatibility complex repertoire in inbred mice does not necessarily predict responses in nonhuman primates and humans, these results suggest that synthetic centralized env immunogens represent a promising approach for HIV-1 vaccine design that merits further characterization

Evidence for Using Alpha-Lipoic Acid in Reducing Lipoprotein and Inflammatory Related Atherosclerotic Risk

Alpha lipoic acid (α-LA) is a potent biological antioxidant that is found naturally in the human body at very low concentrations, primarily in the mitochondria. However, synthetic α-LA is commercially available as a nutritional supplement and has been shown to be effective at ameliorating symptoms in diseases with an underlying oxidative stress component. High blood cholesterol is a major cardiovascular disease (CVD) risk factor and is responsive to diet and lifestyle modifications. In addition to high blood cholesterol, there is increasing evidence that supports the independent role of oxidized lipids and lipoproteins, chiefly oxidized low-density lipoproteins (Ox-LDL), in the development of CVD. Lowering total blood cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG) and raising high-density lipoprotein cholesterol (HDL-C) levels is the most desirable metabolic state for maximum protection against CVD, but can be difficult to achieve through diet and exercise alone. With emerging evidence of reduced LDL-C and TG, increased HDL-C, and blunting of oxidative susceptibility of lipoproteins by α-LA, its use alone or in combination with other dietary supplements may be an effective strategy to modulate multiple metabolic targets of oxidative stress and cholesterol metabolism to reduce CVD risk. This review examines the current evidence for the use of α-LA in CVD risk reduction and identifies the remaining gaps that must be addressed in this area of research