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. 2016 Feb 29:6:22332.
doi: 10.1038/srep22332.

An Inactivated Antibiotic-Exposed Whole-Cell Vaccine Enhances Bactericidal Activities Against Multidrug-Resistant Acinetobacter baumannii

Meng-Hooi Shu  1 , NorAziyah MatRahim  2 , NurAsyura NorAmdan  1 , Sui-Ping Pang  1 , Sharina H Hashim  1 , Wai-Hong Phoon  1 , Sazaly AbuBakar  1
Affiliations

An Inactivated Antibiotic-Exposed Whole-Cell Vaccine Enhances Bactericidal Activities Against Multidrug-Resistant Acinetobacter baumannii

Meng-Hooi Shu et al. Sci Rep. .

Abstract

Vaccination may be an alternative treatment for infection with multidrug-resistance (MDR) Acinetobacter baumannii. The study reported here evaluated the bactericidal antibody responses following immunization of mice using an inactivated whole-cell vaccine derived from antibiotic-exposed MDR A. baumannii (I-M28-47-114). Mice inoculated with I-M28-47 (non-antibiotic-exposed control) and I-M28-47-114 showed a high IgG antibody response by day 5 post-inoculation. Sera from mice inoculated with I-M28-47-114 collected on day 30 resulted in 80.7 ± 12.0% complement-mediated bacteriolysis in vitro of the test MDR A. baumannii treated with imipenem, which was a higher level of bacteriolysis over sera from mice inoculated with I-M28-47. Macrophage-like U937 cells eliminated 49.3 ± 11.6% of the test MDR A. baumannii treated with imipenem when opsonized with sera from mice inoculated with I-M28-47-114, which was a higher level of elimination than observed for test MDR A. baumannii opsonized with sera from mice inoculated with I-M28-47. These results suggest that vaccination with I-M28-47-114 stimulated antibody responses capable of mounting high bactericidal killing of MDR A. baumannii. Therefore, the inactivated antibiotic-exposed whole-cell vaccine (I-M28-47-114) has potential for development as a candidate vaccine for broad clearance and protection against MDR A. baumannii infections.

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Figures

Figure 1
Figure 1. Kinetics of the IgG antibody response to inoculation with I-M28-47 and I-M28-47-114.
The levels of antigen-specific IgG were determined by indirect ELISA in pooled sera from mice inoculated with I-M28-47-114, I-M28-47 (control) or DPBS (placebo control) and challenged on day 14. The data are expressed as the mean ± S.D. absorbance units.
Figure 2
Figure 2. Complement-mediated bacteriolysis activity of sera from mice inoculated with I-M28-47 and I-M28-47-114 against two different MDR A. baumannii growth conditions.
The lysis activity percentages were determined using sera from mice inoculated with I-M28-47-114, I-M28-47 (control) or DPBS (placebo control) in presence of baby rabbit complement against MDR A. baumannii (a) cultured without imipenem treatment or (b) treated with 32 mg/L imipenem. The values are the means ± S.D. tested in duplicate. *P < 0.05 represents significant differences in lysis between the vaccine groups and the placebo control group.
Figure 3
Figure 3. Percentage of opsonophagocytic killing activity following opsonisation with sera from mice inoculated with I-M28-47 and I-M28-47-114.
Opsonization enhances the uptake and killing of MDR A. baumannii (a) cultured without imipenem treatment or (b) treated with 32 mg/L imipenem by macrophage-like U937 and RAW 264.7 cells. All the values are the means ± S.D. tested in duplicate. A significant difference in killing between the vaccine groups and the placebo control groups was observed (*P < 0.05).
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