A novel pentavalent vaccine candidate completely protects against Acinetobacter baumannii in a mouse model of
Yomna A Hagag1, Heba Shehta Said2, Hany I Kenawy3
1Department of Microbiology and Immunology, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Abstract:
Acinetobacter baumannii is considered as one of the most virulent and infectious organisms that have an increased ability to both evade host immune response and resist various classes of antibiotics, leading to life-threatening infections. Multiple virulence factors have been implicated in the high prevalence rate of A. baumannii in hospitalized and immunocompromised patients. Moreover, improper use of antibiotics has led to the emergence of extensive drug-resistant strains that urgently require alternative strategies to control this superbug. Unfortunately, the availability of a licensed vaccine against A. baumannii infections is still challenged by the vast diversity among A. baumannii strains. Here, we report the development of a novel pentavalent vaccine candidate composed of two recombinant proteins (Wza and YiaD) and a pool of capsular polysaccharides isolated from 3 clinical isolates. We tested this new vaccine in vivo in a mouse model of peritonitis against the standard strain ATCC 19606 in addition to 3 clinical isolates of A. baumannii. Immunization with this vaccine completely protected the challenged mice with 100% survival rate in the case of all the tested bacteria. Further clinical studies are urgently needed to evaluate the efficacy and safety of this proprietary vaccine to protect patients from A. baumannii lethal infections. KEY POINTS: • Recombinant proteins pool (Wza and YiaD) immunization led to a synergistic immune response. • Capsular polysaccharides pool induced up to 90% protection of tested clinical isolates. • The pentavalent pool showed superiority with 100% survival of immunized mice.
Insights
A novel pentavalent vaccine combining recombinant proteins and capsular polysaccharides demonstrated 100% protection against Acinetobacter baumannii infections in mice. This breakthrough offers a promising strategy against this dangerous superbug.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Acinetobacter baumannii is a highly virulent pathogen causing life-threatening infections, particularly in hospital settings.
- Extensive drug resistance in A. baumannii necessitates alternative control strategies, including vaccination.
- Strain diversity poses a significant challenge to developing effective A. baumannii vaccines.
Purpose of the Study:
- To develop and evaluate a novel pentavalent vaccine candidate against Acinetobacter baumannii.
- To assess the vaccine's efficacy in a preclinical mouse model.
- To address the challenge of A. baumannii strain diversity with a multi-component vaccine.
Main Methods:
- Development of a pentavalent vaccine using recombinant proteins (Wza, YiaD) and pooled capsular polysaccharides from clinical isolates.
- In vivo testing of the vaccine in a mouse model of peritonitis.
- Challenge with both a standard strain (ATCC 19606) and three clinical isolates of A. baumannii.
Main Results:
- The pentavalent vaccine candidate induced a synergistic immune response.
- Immunization resulted in 100% survival in mice challenged with all tested A. baumannii strains.
- The vaccine demonstrated complete protection against both standard and diverse clinical isolates.
Conclusions:
- The developed pentavalent vaccine candidate is highly effective in a preclinical model.
- This vaccine shows significant potential for controlling Acinetobacter baumannii infections.
- Further clinical studies are warranted to assess the vaccine's efficacy and safety in humans.
