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Radiation-Inactivated Acinetobacter baumannii Vaccine Candidates
Stephen J Dollery1, Daniel V Zurawski2, Elena K Gaidamakova3,4
1Biological Mimetics, Inc., 124 Byte Drive, Frederick, MD 21702, USA.
Abstract:
Acinetobacter baumannii is a bacterial pathogen that is often multidrug-resistant (MDR) and causes a range of life-threatening illnesses, including pneumonia, septicemia, and wound infections. Some antibiotic treatments can reduce mortality if dosed early enough before an infection progresses, but there are few other treatment options when it comes to MDR-infection. Although several prophylactic strategies have been assessed, no vaccine candidates have advanced to clinical trials or have been approved. Herein, we rapidly produced protective whole-cell immunogens from planktonic and biofilm-like cultures of A. baumannii, strain AB5075 grown using a variety of methods. After selecting a panel of five cultures based on distinct protein profiles, replicative activity was extinguished by exposure to 10 kGy gamma radiation in the presence of a Deinococcus antioxidant complex composed of manganous (Mn2+) ions, a decapeptide, and orthophosphate. Mn2+ antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic A. baumannii vaccine candidates. Mice were immunized and boosted twice with 1.0 × 107 irradiated bacterial cells and then challenged intranasally with AB5075 using two mouse models. Planktonic cultures grown for 16 h in rich media and biofilm cultures grown in static cultures underneath minimal (M9) media stimulated immunity that led to 80-100% protection.
Insights
Developing a novel vaccine against multidrug-resistant Acinetobacter baumannii is crucial. Researchers created whole-cell immunogens that successfully protected mice against lethal infections, offering a promising new strategy.
Area of Science:
- Microbiology and Immunology
- Vaccine Development
- Infectious Diseases
Background:
- Acinetobacter baumannii is a multidrug-resistant (MDR) bacterial pathogen causing severe infections like pneumonia and septicemia.
- Existing treatments for MDR A. baumannii infections are limited, and no approved vaccines are available.
- Prophylactic strategies are needed to combat the rising threat of MDR bacterial infections.
Purpose of the Study:
- To rapidly produce protective whole-cell immunogens from Acinetobacter baumannii.
- To develop a replication-deficient vaccine candidate against MDR A. baumannii.
- To evaluate the efficacy of the vaccine candidate in mouse models.
Main Methods:
- Whole-cell immunogens were produced from planktonic and biofilm-like cultures of A. baumannii strain AB5075.
- Replicative activity was eliminated using gamma radiation and a Deinococcus antioxidant complex (manganous ions, decapeptide, orthophosphate).
- Mice were immunized and boosted, then challenged intranasally with A. baumannii to assess protection.
Main Results:
- Immunization with irradiated A. baumannii cells generated protective immunity.
- Vaccine candidates derived from planktonic and biofilm cultures demonstrated significant efficacy.
- 80-100% protection was achieved in mouse models challenged with A. baumannii.
Conclusions:
- Rapidly produced, replication-deficient whole-cell immunogens are effective vaccine candidates against A. baumannii.
- This approach offers a promising strategy for developing a much-needed vaccine against MDR A. baumannii.
- Further development could lead to a viable prophylactic measure against severe A. baumannii infections.
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