Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates
<i>Acinetobacter baumannii</i> 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 infectio...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/2/96 |
| _version_ | 1827597320672247808 |
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| author | Stephen J. Dollery Daniel V. Zurawski Elena K. Gaidamakova Vera Y. Matrosova John K. Tobin Taralyn J. Wiggins Ruth V. Bushnell David A. MacLeod Yonas A. Alamneh Rania Abu-Taleb Mariel G. Escatte Heather N. Meeks Michael J. Daly Gregory J. Tobin |
| author_facet | Stephen J. Dollery Daniel V. Zurawski Elena K. Gaidamakova Vera Y. Matrosova John K. Tobin Taralyn J. Wiggins Ruth V. Bushnell David A. MacLeod Yonas A. Alamneh Rania Abu-Taleb Mariel G. Escatte Heather N. Meeks Michael J. Daly Gregory J. Tobin |
| author_sort | Stephen J. Dollery |
| collection | DOAJ |
| description | <i>Acinetobacter baumannii</i> 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 <i>A. baumannii</i>, 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 <i>Deinococcus</i> antioxidant complex composed of manganous (Mn<sup>2+</sup>) ions, a decapeptide, and orthophosphate. Mn<sup>2+</sup> antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic <i>A. baumannii</i> vaccine candidates. Mice were immunized and boosted twice with 1.0 × 10<sup>7</sup> 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. |
| first_indexed | 2024-03-09T03:28:35Z |
| format | Article |
| id | doaj.art-975d9d8c0a5940009a01e2707c28e8ae |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T03:28:35Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-975d9d8c0a5940009a01e2707c28e8ae2023-12-03T14:59:07ZengMDPI AGVaccines2076-393X2021-01-01929610.3390/vaccines9020096Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine CandidatesStephen J. Dollery0Daniel V. Zurawski1Elena K. Gaidamakova2Vera Y. Matrosova3John K. Tobin4Taralyn J. Wiggins5Ruth V. Bushnell6David A. MacLeod7Yonas A. Alamneh8Rania Abu-Taleb9Mariel G. Escatte10Heather N. Meeks11Michael J. Daly12Gregory J. Tobin13Biological Mimetics, Inc., 124 Byte Drive, Frederick, MD 21702, USAWound Infections Department, Bacterial Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USABiological Mimetics, Inc., 124 Byte Drive, Frederick, MD 21702, USABiological Mimetics, Inc., 124 Byte Drive, Frederick, MD 21702, USABiological Mimetics, Inc., 124 Byte Drive, Frederick, MD 21702, USABiological Mimetics, Inc., 124 Byte Drive, Frederick, MD 21702, USAWound Infections Department, Bacterial Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAWound Infections Department, Bacterial Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USAWound Infections Department, Bacterial Diseases Branch, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USADefense Threat Reduction Agency, Ft. Belvoir, VA 22060, USADepartment of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USABiological Mimetics, Inc., 124 Byte Drive, Frederick, MD 21702, USA<i>Acinetobacter baumannii</i> 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 <i>A. baumannii</i>, 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 <i>Deinococcus</i> antioxidant complex composed of manganous (Mn<sup>2+</sup>) ions, a decapeptide, and orthophosphate. Mn<sup>2+</sup> antioxidants prevent hydroxylation and carbonylation of irradiated proteins, but do not protect nucleic acids, yielding replication-deficient immunogenic <i>A. baumannii</i> vaccine candidates. Mice were immunized and boosted twice with 1.0 × 10<sup>7</sup> 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.https://www.mdpi.com/2076-393X/9/2/96<i>A. baumannii</i>vaccinemousewhole-cellirradiatedprotective |
| spellingShingle | Stephen J. Dollery Daniel V. Zurawski Elena K. Gaidamakova Vera Y. Matrosova John K. Tobin Taralyn J. Wiggins Ruth V. Bushnell David A. MacLeod Yonas A. Alamneh Rania Abu-Taleb Mariel G. Escatte Heather N. Meeks Michael J. Daly Gregory J. Tobin Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates Vaccines <i>A. baumannii</i> vaccine mouse whole-cell irradiated protective |
| title | Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates |
| title_full | Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates |
| title_fullStr | Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates |
| title_full_unstemmed | Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates |
| title_short | Radiation-Inactivated <i>Acinetobacter baumannii</i> Vaccine Candidates |
| title_sort | radiation inactivated i acinetobacter baumannii i vaccine candidates |
| topic | <i>A. baumannii</i> vaccine mouse whole-cell irradiated protective |
| url | https://www.mdpi.com/2076-393X/9/2/96 |
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