The immunogenic characteristics associated with multivalent display of Vi polysaccharide antigen using biodegradable polymer particles

Anish, Chakkumkal; Goswami, Dinesh G.; Kanchan, Vibhu; Mathew, Simi; Panda, Amulya K.

doi:10.1016/j.biomaterials.2012.06.007

Cited by 18 publications

(13 citation statements)

References 52 publications

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“…The selective targeting of MZB cells by antigens in a particulate form may also select for broadly neutralizing cross-reactive antibodies that might be of value for highly mutating viruses. Although other groups have proposed the use of PS entrapped in biodegradable particles, as a vehicle to maintain a sustained release of Ag (57,58), and the ability of PS encapsulated in cross-linked BSA particles to induce the release of IL-8, TNF-α and IL-1β (57), this is the first report to study the adaptive responses to non-covalent associations of PS and protein on the surface of inert particles.…”

Section: Discussionmentioning

confidence: 99%

Noncovalent Association of Protein and Capsular Polysaccharide on Bacteria-Sized Latex Beads as a Model for Polysaccharide-Specific Humoral Immunity to Intact Gram-Positive Extracellular Bacteria

Colino

Duke

Snapper

2013

The Journal of Immunology

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Intact Streptococcus pneumoniae, expressing type 14 capsular polysaccharide (PPS14) and type III Streptococcus agalactiae containing a PPS14 core capsule identical to PPS14, exhibit non-covalent associations of PPS14 and bacterial protein, in contrast to soluble covalent conjugates of these respective antigens. Both bacteria and conjugates induce murine PPS14-specific IgG responses dependent on CD4+ T cells. Further, secondary immunization with conjugate and S. agalactiae, although not S. pneumoniae, results in a boosted response. However, in contrast to conjugate, PPS14-specific IgG responses to bacteria lack affinity maturation, utilize the 44.1-idiotype and are dependent on marginal zone B cells. To better understand the mechanism underlying this dichotomy we developed a minimal model of intact bacteria in which PPS14 and pneumococcal surface protein A (PspA) were stably attached to 1 μm (bacteria-sized) latex beads, but not directly linked to each other, in contrast to PPS14-PspA conjugate. PPS14+[PspA] beads, similar to conjugate, induced in mice boosted PPS14-specific IgG secondary responses, dependent on T cells and ICOS-dependent costimulation, and in which priming could be achieved with PspA alone. In contrast to conjugate, but similar to intact bacteria, the primary PPS14-specific IgG response to PPS14+[PspA] beads peaked rapidly, with the secondary response highly enriched for the 44.1-idiotype and lacking affinity maturation. These results demonstrate that non-covalent association in a particle, of polysaccharide and protein, recapitulates essential immunologic characteristics of intact bacteria that are distinct from soluble covalent conjugates of these respective antigens.

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Section: Discussionmentioning

confidence: 99%

Noncovalent Association of Protein and Capsular Polysaccharide on Bacteria-Sized Latex Beads as a Model for Polysaccharide-Specific Humoral Immunity to Intact Gram-Positive Extracellular Bacteria

Colino

Duke

Snapper

2013

The Journal of Immunology

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“…33 Briefly, an internal aqueous phase (IAP), including 8 mg PHY (75%, No CY150310; Shanxi Ciyuan Biotechnology Co., Ltd., Xian, People's Republic of China) and OVA (Sigma-Aldrich Co., St Louis, MO, USA) dissolved in 0.4 mL deionized water, was emulsified into the organic phase (OP) (30 mg mL −1 PLA in 4 mL acetone solution) (PLA, molecular weight =50 kDa; Shandong Daigang Biotechnology Co., Ltd., Jinan, People's Republic of China) by magnetic stirring for 0.5 h. The obtained primary emulsion (W/O) was added dropwise into the external aqueous phase (EAP) including 0.33% (w/v) of F68 (molecular weight =8,350±1,000; Shanghai Yuanye Biotechnology Co., Ltd., Shanghai, People's Republic of China) in 44 mL deionized water by magnetic stirring to produce the double emulsion. The resulting coarse double emulsion was magnetically stirred for 1.5 h to homogenize the nanospheres for a narrow size distribution.…”

Section: Methodsmentioning

confidence: 99%

Maturation of dendritic cells in vitro and immunological enhancement of mice in vivo by pachyman- and/or OVA-encapsulated poly(D,L-lactic acid) nanospheres

Zheng

Qin

et al. 2018

IJN

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Background Poly lactide (PLA) was proved in the last years to be good for use in sustained drug delivery and as carriers for vaccine antigens. In our previous research, pachyman (PHY)-encapsulated PLA (PHYP) nanospheres were synthesized and their function of controlling drug release was demonstrated. Purpose In order to modify the fast drug-release rate of PHY when inoculated alone, the maturation of bone marrow dendritic cells (BMDCs) in vitro and their immunological enhancement in vivo were explored using PHYP nanospheres. Methods The maturation and antigen uptake of BMDCs were evaluated, both alone and with formulated antigen PHYP nanospheres, ie, ovalbumin (OVA)-loaded PHYP nanospheres, as an antigen delivery system, to investigate antigen-specific humoral and cellular immune responses. Results The results indicated that, when stimulated by PHYP, the BMDCs matured as a result of upregulated expression of co-stimulatory molecules; the mechanism was elucidated by tracing fluorescently labeled antigens in confocal laser scanning microscopy images and observing the uptake of nanospheres by transmission electron microscopy. It was further revealed that mice inoculated with OVA-PHYP had augmented antigen-specific IgG antibodies, increased cytokine secretion by splenocytes, increased splenocyte proliferation, and activation of cluster of differentiation (CD)4 + and CD8 + T cells in vivo. Elevated immune responses were produced by OVA-PHYP, possibly owing to the activation and maturation of dendritic cells (in draining lymph nodes). Conclusion It was corroborated that PHY- and/or OVA-encapsulated PLA nanospheres elicited prominent antigen-presenting effects on BMDCs and heightened humoral and cellular immune responses compared with other formulations.

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“…In another study, Vi polysaccharide delivered by PLA nanoparticles or microparticles induced higher levels of antigen-specific IgG and memory antibody responses than a soluble vaccine. 93 Furthermore, high density of antigens displayed on the surfaces of PLA particles correlated with robust humoral immune responses. These results suggest that engineering of the interface between antigen-displaying vaccine particles and B-cells is crucial to prime strong humoral immunity.…”

Section: Particulate Vaccines Against Category B Bioterrorism Agentsmentioning

confidence: 96%

“…The particulate formulation elicited robust IFN‐γ release from splenocytes in immunized mice and completely protected animals against a lethal challenge. In another study, Vi polysaccharide delivered by PLA nanoparticles or microparticles induced higher levels of antigen‐specific IgG and memory antibody responses than a soluble vaccine . Furthermore, high density of antigens displayed on the surfaces of PLA particles correlated with robust humoral immune responses.…”

Section: Particulate Vaccines Against Category B Bioterrorism Agentsmentioning

confidence: 96%

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

Fan

Moon

2016

WIREs Nanomed Nanobiotechnol

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Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens.

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The immunogenic characteristics associated with multivalent display of Vi polysaccharide antigen using biodegradable polymer particles

Cited by 18 publications

References 52 publications

Noncovalent Association of Protein and Capsular Polysaccharide on Bacteria-Sized Latex Beads as a Model for Polysaccharide-Specific Humoral Immunity to Intact Gram-Positive Extracellular Bacteria

Noncovalent Association of Protein and Capsular Polysaccharide on Bacteria-Sized Latex Beads as a Model for Polysaccharide-Specific Humoral Immunity to Intact Gram-Positive Extracellular Bacteria

Maturation of dendritic cells in vitro and immunological enhancement of mice in vivo by pachyman- and/or OVA-encapsulated poly(D,L-lactic acid) nanospheres

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

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