High-level expression of genes encoding protective antigens
produced by recombinant attenuated Salmonella vaccine strains is desirable to
maximize antibody responses to the protective antigen(s). However, high-level
expression of protective antigens that are of no benefit to the recombinant
attenuated Salmonella vaccine strain causes the strain to grow more slowly and
be less robust in withstanding stresses encountered after oral delivery to an
immunized individual. This can be overcome by administering higher doses but
that is costly and results in vaccinating fewer individuals. Similarly, display
of attenuation can often lessen the ability of vaccine strains to withstand host
imposed stresses and natural defenses to also lessen immune effectiveness.
Investigators at the Biodesign Institute of Arizona State
University have developed technologies to preclude synthesis of protective
antigens by recombinant attenuated Salmonella vaccine until they arrive to the
lymphoid tissues. Thus, the attenuated Salmonella vaccine exhibits a regulated
delayed expression in synthesis of protective antigens. They have also designed
strains with regulated delayed attenuation that is only manifest in vivo after
successful colonization of lymphoid tissues. Both strategies yield more
immunogenic vaccines effective at lower doses.
Potential Applications
- The technology can be used for the development of
numerous types of vaccines to protect agriculturally important animals and
humans against a diversity of pathogens causing infectious diseases in those
individuals.
- There is also a potential for developing vaccines to
immunize companion animals and wildlife populations to eliminate the spread of
zoonotic pathogens that have the potential for transmission to agriculturally
important animals and/or to humans.
Benefits and Advantages
- Economical to manufacture, distribute and administer
- More effective vaccines at lower doses
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