DNA vaccine encoding OmpA and Pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection

Lei, Langhuan; Yang, Feng; Zou, Jintao; Jing, Huaiqi; Zhang, Jin; Xu, Wanting; Zou, Quanming; Zhang, Jinyong; Wang, Xingyong

doi:10.1007/s11033-019-04994-2

Cited by 37 publications

(17 citation statements)

References 44 publications

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“…The Pal proteins of several organisms have been shown to possess excellent vaccinogenic potential [ 32 , 64 , 65 ]. One of the best studied examples is the aforementioned P6 protein, which is considered a lead vaccine candidate for prevention of non-typeable H. influenzae infections in humans (acute otitis media in children, sinusitis, exacerbations in COPD patients, pneumonia).…”

Section: Discussionmentioning

confidence: 99%

The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge

et al. 2020

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Burkholderia mallei is a highly pathogenic bacterium that causes the fatal zoonosis glanders. The organism specifies multiple membrane proteins, which represent prime targets for the development of countermeasures given their location at the host-pathogen interface. We investigated one of these proteins, Pal, and discovered that it is involved in the ability of B. mallei to resist complement-mediated killing and replicate inside host cells in vitro , is expressed in vivo and induces antibodies during the course of infection, and contributes to virulence in a mouse model of aerosol infection. A mutant in the pal gene of the B. mallei wild-type strain ATCC 23344 was found to be especially attenuated, as BALB/c mice challenged with the equivalent of 5,350 LD 50 completely cleared infection. Based on these findings, we tested the hypothesis that a vaccine containing the Pal protein elicits protective immunity against aerosol challenge. To achieve this, the pal gene was cloned in the vaccine vector Parainfluenza Virus 5 (PIV5) and mice immunized with the virus were infected with a lethal dose of B. mallei . These experiments revealed that a single dose of PIV5 expressing Pal provided 80% survival over a period of 40 days post-challenge. In contrast, only 10% of mice vaccinated with a PIV5 control virus construct survived infection. Taken together, our data establish that the Peptidoglycan-associated lipoprotein Pal is a critical virulence determinant of B. mallei and effective target for developing a glanders vaccine.

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Section: Discussionmentioning

confidence: 99%

The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge

et al. 2020

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“…It has been proposed as a potential vaccine candidate owing to its important role in the pathogenesis of the bacteria. 67 Efforts are underway for the vaccine development using OmpA as vaccine target via different technologies, either as a protein-based vaccine 68 , 69 or DNA vaccine (encoding OmpA alone 70 or combination of OmpA with other protein 71 ). All these vaccines are shown to elicit antibodies and to induce promising protective immunity against the bacterium infection.…”

Section: Progress In a Baumannii Vaccine Developmentmentioning

confidence: 99%

“…All these vaccines are shown to elicit antibodies and to induce promising protective immunity against the bacterium infection. 68 , 69 , 70 , 71 Polymorphism of OmpA that resulted in five major bacterium variants, however, may limit the effectiveness of vaccine from a single OmpA variant. 72 In addition to OmpA, other OMPs that have been evaluated for their potential as vaccine candidates are Omp22 73 and BamA.…”

Section: Progress In a Baumannii Vaccine Developmentmentioning

confidence: 99%

Facing the challenges of multidrug-resistant Acinetobacter baumannii : progress and prospects in the vaccine development

MatRahim

Lee

Strych

et al. 2021

Human Vaccines & Immunotherapeutics

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In 2017, the World Health Organization (WHO) named A. baumannii as one of the three antibiotic-resistant bacterial species on its list of global priority pathogens in dire need of novel and effective treatment. With only polymyxin and tigecycline antibiotics left as last-resort treatments, the need for novel alternative approaches to the control of this bacterium becomes imperative. Vaccines against numerous bacteria have had impressive records in reducing the burden of the respective diseases and addressing antimicrobial resistance; as in the case of Haemophilus influenzae type b . A similar approach could be appropriate for A. baumannii. Toward this end, several potentially protective antigens against A. baumannii were identified and evaluated as vaccine antigen candidates. A licensed vaccine for the bacteria, however, is still not in sight. Here we explore and discuss challenges in vaccine development against A. baumannii and the promising approaches for improving the vaccine development process.

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“…Data concerning the impact of MDR A. baumannii are insu cient and controversial. There are currently no approved vaccine offering signi cant protective e cacy against acute A. baumannii infection (7,8). Beyond that, compared to other bacteria, a narrow-spectrum antibiotic is only effective against A. baumannii and in the pipeline to treat or control of this gram-negative bacterium (9).…”

Section: Introductionmentioning

confidence: 99%

Evaluation the Reactivity of a Peptide-Based Monoclonal Antibody with Drug Resistant Pulsotypes of Acinetobacter Baumannii as Potential Therapeutic Approach

Yeganeh¹,

Shabani²,

Pakzad³

et al. 2021

Preprint

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Background: Acinetobacter baumannii is an opportunistic and antibiotic-resistant pathogen that predominantly causes nosocomial infections. There is urgent need for development nonantibiotic-based treatment strategies. We developed novel monoclonal antibody (mAb) against a peptide of conserved outer membrane protein A (OmpA) and evaluated its reactivity with different pulsotypes of A.baumannii. Materials and Methods: Peptide derived from A.baumannii OmpA was conjugated to keyhole limpet hemocyanin and injected into Balb/c mice. Splenocytes of immunized mice were fused with SP2/0 myeloma cells followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, one monoclone was selected as 3F10-C9 and the antibody was tested for reaction with five different Acinetobacter pulsotypes that were resistant to carbapenem antibiotics. The affinity constant was measured by ELISA. The ELISA, Western blotting, indirect immunofluorescence (IFA), and in vitro Opsonophagocytosis assays were used to evaluate the reactivity of generated mAb. Results: The anti-OmpA antibody reacted with the immunizing peptide and had a high affinity (around 1.94 × 10 − 9 M) for its antigen in the ELISA. Specific binding of mAb to OmpA was confirmed in Western blot. IFA assays revealed that mAb recognized specific OmpA on the pulsotypes. Opsonophagocytosis assays showed that the mAb increased bactericidal activity of macrophage cells. The antibody function was higher in the presence of serum complement. Conclusion: The peptide-based mAb demonstrated optimal performance in laboratory experiments which may be appropriate in investigation on OmpA in Acinetobacter pathogenesis and development of passive immunization as novel therapeutic approach.

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DNA vaccine encoding OmpA and Pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection

Cited by 37 publications

References 44 publications

The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge

The Peptidoglycan-associated lipoprotein Pal contributes to the virulence of Burkholderia mallei and provides protection against lethal aerosol challenge

Facing the challenges of multidrug-resistant Acinetobacter baumannii : progress and prospects in the vaccine development

Evaluation the Reactivity of a Peptide-Based Monoclonal Antibody with Drug Resistant Pulsotypes of Acinetobacter Baumannii as Potential Therapeutic Approach

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