Gene-deleted vaccines

Vaccine production is pursued with the objectives to genetically engineer vaccines with specific gene deletions reducing virulence produce viral and bacterial vectored vaccines and develop subunit vaccines using purified antigens obtained from in vitro expression vectors such as pseudorabies purified protein vaccine and foot-and-mouth disease vaccine. 

K. Matsuda, A. A. Chaudhari and J. H. Lee, Safety and efficacy of a virulence gene-deleted live vaccine candidate for fowl typhoid in young chickens. Avian Pathol., 2011, 40, 309-314. 

A randomized, double-blind, placebo-controUed trial using a live oral cholera vaccine (strain CVD 103, derived from the V. cholerae 01 classical Inaba strain 569B by deletion of the genes encoding the A subunit of cholera toxin) was conducted in 50 healthy Swiss adults. There was a significant rise in serum antitoxin titers in 76% of the volunteers. Two vaccinees reported watery stools after immunization (2). 

Sacks WR, Schaffer PA (1987) Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICPO exhibit impaired growth in cell culture. J Virol 61 829-839 Spector FC, Kern ER, Palmer J, Kaiwar R, Cha TA, Brown P, Spaete RR (1998) Evaluation of a live attenuated recombinant virus RAV 9395 as a herpes simplex virus type 2 vaccine in guinea pigs. J Infect Dis 177 1143-1154... 

Clark RH, Kenyon JC, Bartlett NW et al. Deletion of gene A41L enhances vaccinia virus immunoge-nicity and vaccine efficacy. J Gen Virol 2006 87(Pt l) 29-38. 

Veterinary biologies are placed into two Classes, based on the properties of the preparation. Class I products include inactivated r-DNA-derived viral vaccines inactivated r-DNA derived bacterial vaccines viral, bacterial, cytokines or other subunits, monoclonal antibody products and vaccines containing live organisms modified by gene insertion or deletion, without introduction of foreign DNA. 

Infective disease may be induced for several reasons. These include residual pathogenicity due to partial attenuation of pathogens used in vaccines or inadequate activation (as occurred in the infamous Cutter disaster and live poliovirus in humans), genetic recombination for examples where organisms with deleted genes for pathogenicity reacquire them, and reversion to virulence of an otherwise attenuated antigen. 

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