scholarly journals In situ pneumococcal vaccine production and delivery through a hybrid biological-biomaterial vector

2016 ◽  
Vol 2 (7) ◽  
pp. e1600264 ◽  
Author(s):  
Yi Li ◽  
Marie Beitelshees ◽  
Lei Fang ◽  
Andrew Hill ◽  
Mahmoud Kamal Ahmadi ◽  
...  

The type and potency of an immune response provoked during vaccination will determine ultimate success in disease prevention. The basis for this response will be the design and implementation of antigen presentation to the immune system. Whereas direct antigen administration will elicit some form of immunological response, a more sophisticated approach would couple the antigen of interest to a vector capable of broad delivery formats and designed for heightened response. New antigens associated with pneumococcal disease virulence were used to test the delivery and adjuvant capabilities of a hybrid biological-biomaterial vector consisting of a bacterial core electrostatically coated with a cationic polymer. The hybrid design provides (i) passive and active targeting of antigen-presenting cells, (ii) natural and multicomponent adjuvant properties, (iii) dual intracellular delivery mechanisms, and (iv) a simple formulation mechanism. In addition, the hybrid format enables device-specific, or in situ, antigen production and consolidation via localization within the bacterial component of the vector. This capability eliminates the need for dedicated antigen production and purification before vaccination efforts while leveraging the aforementioned features of the overall delivery device. We present the first disease-specific utilization of the vector toward pneumococcal disease highlighted by improved immune responses and protective capabilities when tested against traditional vaccine formulations and a range of clinically relevant Streptococcus pneumoniae strains. More broadly, the results point to similar levels of success with other diseases that would benefit from the production, delivery, and efficacy capabilities offered by the hybrid vector.

2021 ◽  
Author(s):  
Jin Teng, Melody Chung ◽  
Chi Ming Laurence Lau ◽  
Ying Chau

Hydrogel presents as foreign material to the host and participates in immune responses which would skew the biofunctions of immunologic loads (antigen and adjuvants) for in-situ DC priming. This study...


2021 ◽  
Author(s):  
Han Lin ◽  
Chuang Yang ◽  
Min Ge ◽  
Yao Luo ◽  
Xianlong Zhang ◽  
...  

Abstract The development of bacterial vaccines for inducing immunoresponse against infectious diseases such as osteomyelitis is of great significance and importance. However, the responsiveness of bacterial immunotherapy remains far from being satisfactory largely due to the erratic antigen epitopes of bacteria. Herein, we report an in situ vaccination strategy for the immunotherapy of bacterial infection based on an osteomyelitis model using a biomimetic nanomedicine named as HMMP, which was constructed by engineering PpIX-encapsulated hollow MnOx with a hybrid membrane exfoliated from both macrophage and tumor cell lines. The as-established HMMP features a burst bacterial antigen release as the in situ vaccine by the augmented sonodynamic treatment, and the resultant priming of antigen presenting cells for the following activations of both cellular and humoral adaptive immunities against bacterial infections. This treatment regimen not only triggers initial bacterial regression in established osteomyelitis model, also simultaneously generate robust systemic antibacterial immunity against poorly immunogenic secondary osteomyelitis in the contralateral knee as well, and additionally, confers long-lasting bacteria-specific immune memory responses to prevent infection relapse. Thus, our study provides a proof of concept of in situ vaccination for the activation of both innate and adaptive antibacterial immune responses, providing an individual-independent bacterial immunotherapy.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lirong Zhang ◽  
Jingjing Zhang ◽  
Lixia Xu ◽  
Zijian Zhuang ◽  
Jingjin Liu ◽  
...  

Abstract Background Therapeutic tumor vaccine (TTV) that induces tumor-specific immunity has enormous potentials in tumor treatment, but high heterogeneity and poor immunogenicity of tumor seriously impair its clinical efficacy. Herein, a novel NIR responsive tumor vaccine in situ (HA-PDA@IQ/DOX HG) was prepared by integrating hyaluronic acid functionalized polydopamine nanoparticles (HA-PDA NPs) with immune adjuvants (Imiquimod, IQ) and doxorubicin (DOX) into thermal-sensitive hydrogel. Results HA-PDA@IQ NPs with high photothermal conversion efficiency (41.2%) and T1-relaxation efficiency were using HA as stabilizer by the one-pot oxidative polymerization. Then, HA-PDA@IQ loaded DOX via π-π stacking and mixed with thermal-sensitive hydrogel to form the HA-PDA@IQ/DOX HG. The hydrogel-confined delivery mode endowed HA-PDA@IQ/DOX NPs with multiple photothermal ablation performance once injection upon NIR irradiation due to the prolonged retention in tumor site. More importantly, this mode enabled HA-PDA@IQ/DOX NPs to promote the DC maturation, memory T cells in lymphatic node as well as cytotoxic T lymphocytes in spleen. Conclusion Taken together, the HA-PDA@IQ/DOX HG could be served as a theranostic tumor vaccine for complete photothermal ablation to trigger robust antitumor immune responses.


2021 ◽  
Vol 13 (7) ◽  
pp. 7913-7923
Author(s):  
Kelly R. Rhodes ◽  
Ariel Isser ◽  
John W. Hickey ◽  
Elana Ben-Akiva ◽  
Randall A. Meyer ◽  
...  

Nanoscale ◽  
2021 ◽  
Author(s):  
Jie Yu ◽  
Xidong He ◽  
Zigui Wang ◽  
Yu Peng Wang ◽  
Sha Liu ◽  
...  

Immune checkpoint blockade (ICB) therapy in combination with immunogenic death (ICD) triggered by photothermal therapy (PTT) and oxaliplatin (OXA) treatment was expected to elicit both innate and adaptive immune responses...


2019 ◽  
Vol 11 (10) ◽  
pp. 9756-9762 ◽  
Author(s):  
Hanjun Hao ◽  
Mengmeng Sun ◽  
Pengyong Li ◽  
Jiawei Sun ◽  
Xinyu Liu ◽  
...  

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2570-2577 ◽  
Author(s):  
John Stagg ◽  
Sandra Pommey ◽  
Nicoletta Eliopoulos ◽  
Jacques Galipeau

AbstractSeveral studies have demonstrated that marrow stromal cells (MSCs) can suppress allogeneic T-cell responses. However, the effect of MSCs on syngeneic immune responses has been largely overlooked. We describe here that primary MSCs derived from C57BL/6 mice behave as conditional antigen-presenting cells (APCs) and can induce antigen-specific protective immunity. Interferon gamma (IFNγ)-treated C57BL/6 MSCs, but not unstimulated MSCs, cocultured with ovalbumin-specific major histocompatibility (MHC) class II-restricted hybridomas in the presence of soluble ovalbumin-induced significant production of interleukin-2 (IL-2) in an antigen dose-dependent manner (P < .005). IFNγ-treated MSCs could further activate in vitro ovalbumin-specific primary transgenic CD4+ T cells. C57BL/6 MSCs, however, were unable to induce antigen cross-presentation via the MHC class I pathway. When syngeneic mice were immunized intraperitoneally with ovalbumin-pulsed IFNγ-treated MSCs, they developed antigen-specific cytotoxic CD8+ T cells and became fully protected (10 of 10 mice) against ovalbumin-expressing E.G7 tumors. Human MSCs were also studied for antigen-presenting functions. IFNγ-treated DR1-positive human MSCs, but not unstimulated human MSCs, induced significant production of IL-2 when cocultured with DR1-restricted influenza-specific humanized T-cell hybridomas in the presence of purified influenza matrix protein 1. Taken together, our data strongly suggest that MSCs behave as conditional APCs in syngeneic immune responses. (Blood. 2006;107:2570-2577)


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