Characterization of a live attenauted vaccine for protection against multi drug resistant Acinetobacter baumannii
Background. Multi-drug resistant Acinetobacter baumannii (MDR-Ab), an opportunistic pathogen associated with nosocomial and combat related infections sustained by military personnel, is difficult to control due to enhanced multi-drug resistance limiting treatment options. Deletion of the thioredoxin gene (trxA) from a clinical isolate of MDR-Ab resulted in a 100-fold increase in LD50 relative to the wild type strain. Thus, the objective of this study was to test the efficacy of this attenuated strain as an attenuated live vaccine against MDR-Ab.
Methods. Mice were vaccinated by either intraperitoneal (i.p.) or subcutaneous (s.c.) injection of 2 x 105 CFU of the DtrxA mutant and boosted 14 days later with an equivalent inoculum. Mice were challenged 30 days post-vaccination by i.p. injection with 10 x LD50 of the WT Ci79 strain. Efficacy of the vaccine was also evaluated by monitoring antibody titers, measuring MDR-Ab specific cytokine production after vaccination, observing pathology and organ burden after challenge, and measuring pentraxin-3 production in vaccinated mice before and after challenge.
Results. Mice vaccinated with the DtrxA mutant were 100% protected against a lethal challenge of Ci79 regardless of vaccination route. Surprisingly, little if any immunoglobulin class switching was observed with IgM predominating. Spleens harvested from vaccinated mice exhibited negligible levels of IL-4, IFNγ and IL-17 production when stimulated with UV killed WT Ci79. Importantly, tissues obtained from vaccinated mice displayed reduced pathology and organ burden compared to tissues from non-vaccinated mice. Lastly, pentraxin-3 was not upregulated 24 hours after challenge in vaccinated mice.
Conclusions. The attenuated DtrxA mutant provides protection against a lethal dose of the WT strain, most likely through a T-cell independent mechanism. Additional studies are currently underway to evaluate cross strain protection and to further elucidate the exact mechanism of protection.