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. 2023;26(5):564-571.
doi: 10.22038/IJBMS.2023.67394.14775.

LDH as an adjuvant makes Brucella outer-membrane vesicles and outer-membrane vesicle-associated proteins highly protective in mice

Xiaoyu Deng  1   2   3 , Jinke He  4   3 , Jinfeng Xu  2   5   3 , Yueli Wang  1   2 , Jihai Yi  1   2 , Huan Zhang  1   2 , Yong Wang  1   2 , Zhen Wang  1   2 , Chuangfu Chen  1   2
Affiliations

LDH as an adjuvant makes Brucella outer-membrane vesicles and outer-membrane vesicle-associated proteins highly protective in mice

Xiaoyu Deng et al. Iran J Basic Med Sci. 2023.

Abstract

Objectives: Existing Brucella vaccines are attenuated and can cause vaccine-associated brucellosis; and these safety concerns have affected their application. Although subunit vaccines have the advantages of safety, efficacy, low cost, and rapid production, they are usually poorly immunogenic and insufficient to trigger persistent immunity. Therefore, we added layered double hydroxide (LDH) as an adjuvant to Brucella subunit vaccine formulations to enhance the immune response to the antigen.

Materials and methods: LDH and Freund's adjuvant were combined with Brucella outer-membrane vesicles (OMVs) and OMV-associated proteins to form a subunit vaccine, respectively. The immunogenicity of LDH as an adjuvant was assessed in BALB/c mice. We examined levels of immunoglobulin G, G1, and G2a (IgG, IgG1, and IgG2a) antibodies (aBs); percentages of Cluster of Differentiation 4-positive (CD4+) and CD8+ T cells in peripheral-blood lymphocytes; and secretion of cytokines in mouse spleen lymphocytes. Finally, splenic index and splenic bacterial load were assessed via Brucella challenge experiments on mice.

Results: The LDH subunit vaccine also produced high levels of specific aBs in mice compared with Freund's adjuvant subunit vaccine and induced mainly T-helper 1 cell (Th1)-type immune responses. In addition, mice in the LDH subunit vaccine group had significantly lower bacterial loads in their spleens than those in the Freund's adjuvant subunit vaccine group, and the LDH-OMV vaccine offered a higher level of protection against Brucella attack.

Conclusion: LDH as an adjuvant-paired vaccine provided a high level of protection against Brucella infection.

Keywords: Adjuvant; Brucella; Immunogenicity; Outer-membrane vesicles; Vaccine.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Identification of outer membrane vesicles (OMVs) and outer membrane protein complexes (OMP)
Figure 2
Figure 2
Identification of outer membrane protein BP26 and outer membrane protein OMP10
Figure 3
Figure 3
Changes in serum antibody levels in mice after post-vaccination
Figure 4
Figure 4
Cytokines produced by spleen cells from mice immunized with either the Freund’s adjuvant group or the LDH adjuvant group
Figure 5
Figure 5
Analysis of spleen index in mice after brucella M5 challenge
See this image and copyright information in PMC

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