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New technologies in developing recombinant attenuated Salmonella vaccine vectors
Shifeng Wang1, Qingke Kong, Roy Curtiss
1Center for Infectious Diseases and Vaccinology, The Biodesign Institute and School of Life Sciences, Arizona State University, Tempe, AZ 85287-5401, USA.
Microbial Pathogenesis
|November 13, 2012
Summary
Recombinant attenuated Salmonella vaccine (RASV) vectors are engineered for oral immunization. Novel strategies enhance vaccine safety and efficacy, leading to a low-cost, multivalent pneumococcal vaccine candidate for infants.
Area of Science:
- * Vaccinology and microbial genetics.
- * Development of live bacterial vaccine vectors.
Background:
- * Recombinant attenuated Salmonella vaccine (RASV) vectors require specific traits for oral immunization success.
- * Effective RASVs must survive the gastrointestinal tract, colonize lymphoid tissues, and induce long-lasting immunity without causing disease.
Purpose of the Study:
- * To enhance the safety and efficacy of RASV vectors.
- * To develop a novel, low-cost, multivalent RASV for protection against Streptococcus pneumoniae.
Main Methods:
- * Utilized regulated delayed in vivo attenuation and antigen synthesis for efficient colonization and antigen production.
- * Incorporated lipid A modification to reduce inflammation and outer membrane vesicles (OMVs) for increased efficiency.
- * Employed a dual-plasmid system with Asd+ and DadB+ selection markers for multivalent antigen expression.
Main Results:
- * Developed strategies for improved RASV survival, colonization, and immune response induction.
- * Demonstrated reduced inflammatory responses through lipid A modification.
- * Created a novel RASV synthesizing multiple pneumococcal protein antigens using a dual-plasmid system.
Conclusions:
- * The novel RASV technology offers a promising approach for developing safe and effective oral vaccines.
- * This low-cost, multivalent vaccine candidate could provide broad protection against diverse Streptococcus pneumoniae serotypes.
- * The vaccine is potentially suitable for newborns and infants, addressing a critical public health need.
