No abstract

Next generation influenza vaccines containing conserved antigens may enhance immunity against seasonal or pandemic influenza virus strains. Using a plasmid DNA (pDNA)-based vaccine approach, we systematically tested combinations of NP, M1 and M2 antigens derived from consensus sequences for protection against lethal influenza challenge and compared formulations for adjuvanting low pDNA vaccine doses. The highest level of protection at the lowest pDNA doses was provided by Vaxfectin™-formulated NP + M2. Vaxfectin™ adjuvanticity was confirmed with a low dose of HA pDNA. These promising proof-of-concept data support the clinical development of Vaxfectin™-formulated pDNA encoding NP + M2 consensus proteins.

No abstract

The results suggest that the CRL1005/BAK/pDNA formulation may enhance immunogenicity by improving the delivery of pDNA-based vaccines. This formulation is currently being evaluated for the prevention of CMV-associated disease in a phase 2 clinical trial.

The loss of mitochondrial function has been implicated in a number of maladies such as Huntington's Disease, Parkinson's Disease, cancer and cardiovascular disease. The objective of this research was to develop a radiolabeled mitochondrial probe. Two tracers, 7′-Z-iodorotenol and 7′-Z-iodorotenone, analogs of rotenone a natural product that inhibits Complex I of the mitochondrial electron transport chain, have been labeled with iodine-125 in 45-85% yield in a single step from the corresponding tribuytylstannyl precursor. In vivo distribution in adult male Sprague-Dawley rats for both compounds showed high accumulation in the heart (1.7-3.7 %ID/g at 1h), a tissue with high mitochondrial content. Z-Iodorotenol did not washout of most tissues between 1 and 2 h post injection whereas Z-iodorotenone showed moderate washout (7-26%) over the same period. By 24 h there was significant loss of both compounds from most tissues including the heart. Heart-to-blood, -lung and -liver ratios for Z-iodorotenone of 28.9, 10.7 and 2.4, respectively, were two-to four-fold higher than the Z-iodorotenol ratios. Compared to the current clinical perfusion tracers, 99m Tc-sestamibi and 99m Tc-tetrofosmin, Z-iodorotenone demonstrates similar 1h heart accumulation and significantly higher heart-to-lung ratio (P <0.001). Z-Iodorotenone heart-to-liver ratio is equivalent to 99m Tcsestamibi. 7′-Z-Iodorotenone possesses distribution characteristics of an improved tracer for SPECT perfusion studies.