[August 10, 2006] Researchers' data from the People's Republic of China, United Kingdom and United States advance vaccines research Tweet (Science Letter Via Thomson Dialog NewsEdge) Data on vaccines are outlined in reports from the People's Republic of China, United Kingdom and United States. Study 1: Researchers have constructed a recombinant adenovirus expressing the capsid protein of porcine circovirus 2 (PCV2). "Porcine circovirus 2 (PCV2) has been implicated as the etiological agent of some diseases, mainly post-weaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS). The capsid (Cap) protein encoded by the PCV2 ORF2 gene may be an excellent candidate for vaccination," investigators in China noted. "In this study, the Cap protein gene was amplified by PCR, and cloned into the transfer vector pShuttle-CMV," said Xianwei Wang and colleagues at Nanjing Agriculture University. "After co-transformation of PmeI-linearized recombinant plasmid pShuttle-CMV-ORF2 and the bone vector pAdEasy-I into Escherichia coli bacteria strain BJ5183, recombinant plasmid containing Cap protein gene (pAd-ORF2) was obtained and identified with PCR. Upon transfection of PacI-linearized plasmid pAd-ORF2 in 293 cell line, a recombinant adenovirus was obtained and named as rAd-Cap with viral titer of 1013.0 TCLD50/mL. The expression of the Cap protein in the 293 cells infected with rAd-Cap, was confirmed with specific antibody to PCV2 by Western blotting and IPMA." "Mice were inoculated with 108, 1010, and 1012 TCID50/mouse of rAd-Cap and boosted two weeks later, and they could generate antibody against PCV2 detected by indirect ELISA, Western blot, and neutralizing activity assay," stated the scientists. "It indicated that the rAd-Cap was able to express the capsid of PCV2 and could elicit immune responses against the PCV2 in mice." "The recombinant adenovirus might be an attractive candidate vaccine for preventing the disease associated with PCV2 infection," they suggested. Wang and associates published their study in Vaccine (Construction and immunogenicity of recombinant adenovirus expressing the capsid protein of porcine circovirus 2 (PCV2) in mice. Vaccine, 2006;24(16):3374-3380). For additional information, contact Ping Jiang, Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agriculture University, Nanjing 210095, People's Republic of China. [email protected]. Study 2: Immunodominant vaccinia-specific CTL responses limit the effectiveness of poxviruses in recombinant vaccination strategies. According to recent research published in the Journal of Immunology, "Many recombinant poxviral vaccines are currently in clinical trials for cancer and infections diseases. However, these agents have failed to generate T cell responses specific for recombinant gene products at levels comparable with T cell responses associated with natural viral infections. The recent identification of vaccinia-encoded CTL epitopes, including a new epitope described in this study, allows the simultaneous comparison of CTL responses specific for poxviral and recombinant epitopes." "We performed detailed kinetic analyses of CTL responses in HLA-A*0201 patients receiving repeated injections of recombinant modified vaccinia Ankara encoding a string of melanoma tumor antigen epitopes," said Caroline L. Smith at Oxford University and collaborators in England, the U.S., and Australia. "The vaccine-driven CTL hierarchy was dominated by modified vaccinia Ankara epitope-specific responses, even in patients who had not received previous smallpox vaccination." "The only recombinant epitope that was able to impact on the CTL hierarchy was the melan-A26-35 analog epitope, whereas responses specific for the weaker affinity epitope NY-ESO-1157-165 failed to be expanded above the level detected in prevaccination samples," reported Smith and her colleagues. "Our results demonstrate that immunodominant vaccinia-specific CTL responses limit the effectiveness of poxviruses in recombinant vaccination strategies and that more powerful priming strategies are required to overcome immunodominance of poxvirus-specific T cell responses." Smith and her coauthors published their study in the Journal of Immunology (Immunodominance of poxviral-specific CTL in a human trial of recombinant-modified vaccinia Ankara. J Immunol, 2005;175(12):8431-8437). For additional information, contact Vincenzo Cerundolo, Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford OX3 9DS, England. Study 3: An adenovirus vector with a chimeric fiber incorporating stabilized single chain antibody achieves targeted gene delivery. Scientists writing in the journal Gene Therapy report, "Adenovirus (Ad) vectors are of utility for many therapeutic applications. Strategies have been developed to alter adenoviral tropism to achieve a cell-specific gene delivery capacity employing fiber modifications allowing genetic incorporation of targeting motifs. In this regard, single chain antibodies (scFv) represent potentially useful agents to achieve targeted gene transfer. However, the distinct biosynthetic pathways that scFv and Ad capsid proteins are normally routed through have thus far been problematic with respect to scFv incorporation into the Ad capsid." "Utilization of stable scFv, which also maintain correct folding and thus functionality under intracellular reducing conditions, could overcome this restriction," said Susan J. Hedley and collaborators at VectorLogics, Inc. and University of Alabama in the U.S. and ESBATech AG in Switzerland. "We genetically incorporated a stable scFv into a de-knobbed, fibritin-foldon trimerized Ad fiber and demonstrated selective targeting to the cognate epitope expressed on the membrane surface of cells." The researchers noted, "We have shown that the scFv employed in this study retains functionality and that stabilizing the targeting molecule, per se, is critical to allow retention of antigen recognition in the adenovirus capsid-incorporated context." Hedley and her coauthors published their study in Gene Therapy (An adenovirus vector with a chimeric fiber incorporating stabilized single chain antibody achieves targeted gene delivery. Gene Ther, 2006;13(1):88-94). Additional information can be obtained by contacting David T. Curiel, Division of Human Gene Therapy, University of Alabama, 901 19th Street S, BMR2 502, Birmingham, AL 35294, USA. [email protected]. Keywords: Birmingham, Alabama, United States, Vaccine Vector, Vector Development, Adenovirus Vector, DNA Vaccine, Vaccine Development, Immunology, Immunotherapy, Gene Therapy, Virology. This article was prepared by Science Letter editors from staff and other reports. Copyright 2006, Science Letter via NewsRx.com. [ Back To TMCnet.com's Homepage ]