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Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Whole-cell vaccine candidates induce a protective response against virulent Acinetobacter baumannii
Stephen J Dollery1, Daniel V Zurawski2, Ruth V Bushnell1
1Biological Mimetics, Inc., Frederick, MD, United States.
Abstract:
Acinetobacter baumannii causes multi-system diseases in both nosocomial settings and a pre-disposed general population. The bacterium is not only desiccation-resistant but also notoriously resistant to multiple antibiotics and drugs of last resort including carbapenem, colistin, and sulbactam. The World Health Organization has categorized carbapenem-resistant A. baumannii at the top of its critical pathogen list in a bid to direct urgent countermeasure development. Several early-stage vaccines have shown a range of efficacies in healthy mice, but no vaccine candidates have advanced into clinical trials. Herein, we report our findings that both an ionizing γ-radiation-inactivated and a non-ionizing ultraviolet C-inactivated whole-cell vaccine candidate protects neutropenic mice from pulmonary challenge with virulent AB5075, a particularly pathogenic isolate. In addition, we demonstrate that a humoral response is sufficient for this protection via the passive immunization of neutropenic mice.
Insights
New whole-cell vaccines inactivated by radiation or UV light protect mice against Acinetobacter baumannii lung infections. Humoral immunity alone is sufficient for protection, offering a promising avenue for vaccine development.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Acinetobacter baumannii is a critical pathogen causing severe diseases, known for its resistance to antibiotics like carbapenems and colistin.
- The World Health Organization highlights carbapenem-resistant A. baumannii as a top priority for developing new countermeasures.
- Existing vaccine candidates have shown limited efficacy in mice, with none progressing to clinical trials.
Purpose of the Study:
- To evaluate the protective efficacy of whole-cell Acinetobacter baumannii vaccine candidates against pulmonary challenge.
- To determine if humoral immunity is sufficient for protection against A. baumannii infection.
- To compare the effectiveness of gamma radiation-inactivated versus ultraviolet C-inactivated vaccines.
Main Methods:
- Development and inactivation of whole-cell A. baumannii vaccine candidates using gamma radiation and ultraviolet C.
- Pulmonary challenge model using virulent AB5075 isolate in neutropenic mice.
- Assessment of vaccine efficacy through survival rates and passive immunization studies.
Main Results:
- Both gamma radiation-inactivated and UV-inactivated whole-cell vaccines conferred significant protection in neutropenic mice against A. baumannii pulmonary infection.
- Passive immunization with antibodies demonstrated that a humoral immune response is sufficient to protect against virulent A. baumannii challenge.
- The study identified effective inactivation methods for whole-cell vaccine development.
Conclusions:
- Whole-cell vaccines against Acinetobacter baumannii, inactivated by either gamma radiation or UV-C, are effective in protecting against lethal pulmonary challenge in a relevant mouse model.
- Humoral immunity plays a crucial role and is sufficient for protection, suggesting antibody-based therapies or vaccines are viable strategies.
- These findings support the advancement of whole-cell A. baumannii vaccines towards clinical evaluation.
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