The VesiVax system: a method for rapid vaccine development
FRONTIERS IN BIOSCIENCE-LANDMARK
Authors: Fujii, Gary; Ernst, William; Adler-Moore, Jill
Abstract
The VesiVax (R) system is based upon the concept that highly potent vaccines can be designed by engineering proteins that are capable of stably inserting themselves into liposomes. Such a nanoscale liposomal particle can then serve as an immunogen for vaccine development. The VesiVax (R) vaccine technology platform is designed to make it relatively easy to engineer and produce new vaccines quickly. Vaccines based on the VesiVax (R) system have been designed against the influenza virus and herpes simplex type 2 virus, the causative agents of the "flu" and genital herpes, respectively. Both vaccines have been tested in animal models and have demonstrated significant protective efficacy from challenge with lethal doses of virus. Assays of the immunological parameters suggest that both T and B cell responses can be elicited by VesiVax (R) vaccines. The safety profile of the VesiVax (R) vaccines is expected to be much better than that of vaccines prepared by conventional techniques. Taken together, the inherent flexibility of the VesiVax platform is expected to facilitate the rapid development of new vaccines which are effective at stimulating protective immune responses.
Mutational pressure is a cause of inter- and intragenomic differences in GC-content of simplex and varicello viruses
COMPUTATIONAL BIOLOGY AND CHEMISTRY
Authors: Khrustalev, Vladislav Victorovich; Barkovsky, Eugene Victorovich
Abstract
Total GC-content (G + C), GC-content in codon positions and 0-fold, 2-fold and 4-fold degenerated sites in all coding districts from 10 completely sequenced genomes of simplex and varicello viruses have been calculated by the original "Coding Genome Scanner" algorithm. The low coefficient of correlation (R < 0.5) between 3GC and G + C in all coding districts from unique regions (UL and US) of alphaherpesvirus genome is a new criterion of the strong mutational pressure that is the process of increasing the rates of nonsynonymous mutations because of the extreme saturation (GC-pressure) or desaturation (AT-pressure) of third (liberal) codon positions with G and C. Unique regions of HSV1, HSV2, CeHV1, CeHV2, CeHV16 and BoHV5 are under the influence of strong GC-pressure caused mostly by AT to GC transversions. Unique regions of EqHV1 are under the influence of weak GC-pressure. In unique regions of CeHV9 AT-pressure is strong; in EqHV4 and VZV unique regions AT-pressure is weak. Mutational AT-pressure in CeHV9 and VZV is caused mostly by transitions, while in EqHV4 it is caused mostly by transversions. The level of 3GC in coding districts situated in long terminal inverted repeats (LTR) of all these viruses is much higher than in coding districts from UL and US. Higher GC-content does not seem to depend on the gene itself, but it does depend on its location. V67 gene of EqHV1 is situated in LTR (3GC = 0.853), while V67 gene of EqHV4 is situated in US (3GC = 0.397). Higher rates of AT to GC transversions in coding districts situated in LTR should be due to the "anatomy" of long terminal inverted repeats. The process of AT to GC transversions is thought to take place only in doublestranded DNA. Indeed, in the potential secondary structure formed by singlestranded genomic DNA of alphaherpesviruses only joined inverted repeats should be doublestranded. (C) 2009 Elsevier Ltd. All rights reserved.