Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against Burkholderia mallei

Abstract

Burkholderia mallei (Bm) is a facultative intracellular pathogen and the etiological agent of glanders, a highly infectious zoonotic disease occurring in equines and humans. The intrinsic resistance to antibiotics, lack of specific therapy, high mortality, and history as a biothreat agent, prompt the need of a safe and effective vaccine. However, the limited knowledge of protective Bm-specific antigens has hampered the development of a vaccine. Further, the use of antigen-delivery systems that enhance antigen immunogenicity and elicit robust antigen-specific immune responses has been limited and could improve vaccines against Bm. Nanovaccines, in particular gold nanoparticles (AuNPs), have been investigated as a strategy to broaden the repertoire of vaccine-mediated immunity and as a tool to produce multivalent vaccines. To synthesize a nano-glycoconjugate vaccine, six predicted highly immunogenic antigens identified by a genome-wide bio- and immuno-informatic analysis were purified and coupled to AuNPs along with lipopolysaccharide (LPS) from B. thailandensis. Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal Bm infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against Bm.

Predictive and Experimental Immunogenicity of Burkholderia Collagen-like Protein 8-Derived Antigens

“…Numerous vaccine candidates have been investigated, ranging from live-attenuated bacteria [3] to subunit acellular vaccines [9,11,32,38,39], all with varying survival and protection efficacies. There is growing support for multivalent vaccines where the combined proteins and polysaccharides elicit effective and simultaneous humoral and cell-mediated responses [15,40]. Additionally, outer membrane proteins like Bucl8 have been targeted for vaccines because their surface-exposed components elicit recognition by the immune system, can be conserved, and expression is often vital for bacteria.…”

“…Additionally, outer membrane proteins like Bucl8 have been targeted for vaccines because their surface-exposed components elicit recognition by the immune system, can be conserved, and expression is often vital for bacteria. Notable examples of OMPs targeted in Burkholderia include OmpW [11,15,41], OmpA [42,43], and Omp85 [32]. Here, we predict and then assess experimentally several novel antigens derived from the recently identified outer membrane protein found in Burkholderia, Bucl8.…”

“…Capsular polysaccharide and lipopolysaccharide have also been used as single antigens or in combination with other antigens, such as Hcp1, to augment a response [9]. Current vaccine approaches include immunization with Burkholderia-derived outer membrane vesicles [12,13] and gold-nanoparticle conjugates [14,15] of promising antigen candidates: Hcp1, capsular polysaccharide, and OmpW [11]. Additionally, several live attenuated vaccine strategies have been examined with varying results [3,16,17].…”

Optimization of Multivalent Gold Nanoparticle Vaccines Eliciting Humoral and Cellular Immunity in an In Vivo Model of Enterohemorrhagic Escherichia coli O157:H7 Colonization

“…AuNPs, 15 nm in diameter, were synthesized, conjugated to individual proteins, and characterized as previously described ( 25 – 27 ). Briefly, 1 mM gold(III) chloride trihydrate underwent a reduction reaction with 90 mM sodium citrate dihydrate.…”

Nanotechnology-Based Delivery Systems for Antimicrobial Peptides

“…The use of AuNPs, among other nanomaterials, in the regulation of the immune system by developing prophylactic and therapeutic vaccines are currently considered a promising biomedical application. Based on AuNPs' parameters, they can be used as immunogens or as a vehicle for adjuvants and antigens [171,172] The size of AuNPs influences their uptake and internalization by cells, 3 nm AuNPs were taken up by cells through pinocytosis and were nontoxic, nonimmunogenic, and repressed ROS generation [173]. The uptake of 60 nm AuNP by cells were through endocytosis.…”