BauA and Omp34 surface loops trigger protective antibodies against Acinetobacter baumannii in a murine sepsis model

Akbari, Zahra; Rasooli, Iraj; Ghaini, Mohammad Hossein; Chaudhuri, Somshukla; Andisi, Vahid Farshchi; Jahangiri, Abolfazl; Ramezanalizadeh, Fatemeh; Schryvers, Anthony B.

doi:10.1016/j.intimp.2022.108731

Cited by 17 publications

(8 citation statements)

References 40 publications

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“…BauA extracellular loop 8 554-576 , loop 7 507-526 and loop 5 396-435 ( Figure 1 ) were selected for insertion into sites 1, 3 and 4 of LCLv3 respectively ( Figures 2C, D ). The loop7 hybrid antigen has also been used in a recently published study ( 29 ).…”

Section: Methodsmentioning

confidence: 99%

Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection

et al. 2022

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Acinetobacter baumannii is a human bacterial pathogen of increasing concern in clinical settings due to the emergence of antibiotic resistant strains and the lack of effective therapeutics. Researchers have been exploring new treatment options such as novel drug candidates and vaccines to prevent severe infections and mortality. Bacterial surface antigens that are essential to A. baumannii for acquiring micronutrients (e.g. iron, zinc) from nutrient restricted environments are being considered as targets for vaccines or immunotherapy due to their crucial role for growth and pathogenesis in the human host. BauA, the outer membrane receptor for the siderophore acinetobactin was targeted for vaccine development in this study. Due to challenges in the commercial production of membrane proteins for vaccines, a novel hybrid antigen method developed by our group was used. Exposed loops of BauA were selected and displayed on a foreign scaffold to generate novel hybrid antigens designed to elicit an immune response against the native BauA protein. The potential epitopes were incorporated into a scaffold derived from the C-lobe of Neisseria meningitidis transferrin binding protein B (TbpB), named the loopless C-lobe (LCL). Hybrid proteins displaying three selected loops (5, 7 and 8) individually or in combination were designed and produced and evaluated in an A. baumannii murine sepsis model as vaccine antigens. Immunization with the recombinant BauA protein protected 100% of the mice while immunization with hybrid antigens displaying individual loops achieved between 50 and 100% protection. The LCL scaffold did not induce a protective immune response, enabling us to attribute the observed protection elicited by the hybrid antigens to the displayed loops. Notably, the mice immunized with the hybrid antigen displaying loop 7 were completely protected from infection. Taken together, these results suggest that our hybrid antigen approach is a viable method for generating novel vaccine antigens that target membrane surface proteins necessary for bacterial growth and pathogenesis and the loop 7 hybrid antigen can be a foundation for approaches to combat A. baumannii infections.

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Section: Methodsmentioning

confidence: 99%

Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection

et al. 2022

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“…Mice were immunized with a hybrid antigen composed of BauA and immunogenic loops of Omp33-36 and LCL. The 7-day survival rate of mice vaccinated with hybrid antigens (71.43%) was higher than that of mice immunized with Omp33-36 immunogenic loop alone (42.86%) (28). The survival rate of mice immunized with recombinant Omp33-36 (rOmp33-36) was 100% under stimulation with A. baumannii (29).…”

Section: Omp33-36mentioning

confidence: 99%

Subunit vaccines for Acinetobacter baumannii

et al. 2023

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Acinetobacter baumannii is a gram-negative bacterium and a crucial opportunistic pathogen in hospitals. A. baumannii infection has become a challenging problem in clinical practice due to the increasing number of multidrug-resistant strains and their prevalence worldwide. Vaccines are effective tools to prevent and control A. baumannii infection. Many researchers are studying subunit vaccines against A. baumannii. Subunit vaccines have the advantages of high purity, safety, and stability, ease of production, and highly targeted induced immune responses. To date, no A. baumannii subunit vaccine candidate has entered clinical trials. This may be related to the easy degradation of subunit vaccines in vivo and weak immunogenicity. Using adjuvants or delivery vehicles to prepare subunit vaccines can slow down degradation and improve immunogenicity. The common immunization routes include intramuscular injection, subcutaneous injection, intraperitoneal injection and mucosal vaccination. The appropriate immunization method can also enhance the immune effect of subunit vaccines. Therefore, selecting an appropriate adjuvant and immunization method is essential for subunit vaccine research. This review summarizes the past exploration of A. baumannii subunit vaccines, hoping to guide current and future research on these vaccines.

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“…This analogous operation is also applied to Omp34 in the latest study, the superior protection of Omp34 loop 3 also proves the hybrid antigen strategy is a viable method (Golestani et al, 2022 ). The combination of BauA loop 7 and Omp34 loop 3 brought 71.43% protection, higher than alone immunization (Akbari et al, 2022 ).…”

Section: Vaccinementioning

confidence: 99%

Non-antibiotic prevention and treatment against Acinetobacter baumannii infection: Are vaccines and adjuvants effective strategies?

Zhang

Deng

et al. 2023

Front. Microbiol.

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Acinetobacter baumannii (A. baumannii) is a Gram-negative opportunistic pathogen widely attached to the surface of medical instruments, making it one of the most common pathogens of nosocomial infection, and often leading to cross-infection and co-infection. Due to the extensive antibiotic and pan-resistance, A. baumannii infection is facing fewer treatment options in the clinic. Therefore, the prevention and treatment of A. baumannii infection have become a tricky global problem. The requirement for research and development of the new strategy is urgent. Now, non-antibiotic treatment strategies are urgently needed. This review describes the research on A. baumannii vaccines and antibacterial adjuvants, discusses the advantages and disadvantages of different candidate vaccines tested in vitro and in vivo, especially subunit protein vaccines, and shows the antibacterial efficacy of adjuvant drugs in monotherapy.

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BauA and Omp34 surface loops trigger protective antibodies against Acinetobacter baumannii in a murine sepsis model

Cited by 17 publications

References 40 publications

Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection

Hybrid antigens expressing surface loops of BauA from Acinetobacter baumannii are capable of inducing protection against infection

Subunit vaccines for Acinetobacter baumannii

Non-antibiotic prevention and treatment against Acinetobacter baumannii infection: Are vaccines and adjuvants effective strategies?

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