While rapid identification of pathogens, novel therapeutic interventions, and passive immunization have critical roles in disease control, none can substitute for pre-existing protective immunity. Mucosally delivered bacterial live vector vaccines represent a practical and effective strategy for immunization. In live vector vaccines, genes that encode protective antigens of unrelated pathogens are expressed in an attenuated vaccine strain and delivered mucosally to generate relevant local and systemic immune responses. We hypothesize that by appropriate manipulation of novel Salmonella enterica serovar Typhi live vector platform technologies, we can construct a mucosally administered bivalent vaccine against potentially lethal infections caused by Acinetobacter baumannii. Our unique research strategy is designed to remodel the outer membrane of an attenuated S. Typhi-based live vector vaccine into an antigen presentation platform in which protective outer membrane antigens from A. baumannii are mucosally delivered to immune inductive sites via a novel inducible outer membrane vesicle delivery system. Mucosal delivery of recombinant outer membrane vesicles (rOMVs) via live vector vaccines offers significant advantages over conventional acellular OMV-based vaccination strategies including: 1] sustained in vivo delivery to mucosal inductive sites, and 2] delivery of rOMVs enriched in properly folded protective antigens. To enhance delivery of these protective antigens to immune effector cells, thereby improving the protective efficacy of this mucosal vaccine, we enhance delivery of rOMVs through inducible over-expression of the hypervesiculating protein PagL. If successful, our novel and highly innovative approach could result in a mucosal live carrier vaccine, effective against potentially lethal systemic and pulmonary infections with A. baumannii, which could prove highly valuable in both civilian and military settings.
1. What is a carrier vaccine?
2. How can carrier vaccines be used to combat the antibiotic resistance crisis in public health?