Controlled release microparticles for vaccine development

O’Hagan, Derek T.; Jeffery, H.; Roberts, Martin; McGee, John P.; Davis, S.S.

doi:10.1016/0264-410x(91)90295-h

Cited by 143 publications

(71 citation statements)

References 16 publications

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“…The mechanism(s) which allows alum to initiate Th2 responses against adsorbed antigens remains unclear, although the responses have been shown to be independent of the key Th2-associated cytokines, interleukin-4 or interleukin-13, and signaling via the signal transducer and activation of transcription-6 (STAT-6) (5). The biodegradable and biocompatible polyester polymers, such as PLA-co-glycolides, poly-D,L-lactide-co-glycolic acid, and PLA, although used for many years as suture material and as controlled-release drug delivery systems (49,53), had their adjuvant effects achieved through the encapsulation of antigens (46,48). Applications from cancer therapy (21,22) to infectious diseases (57,59) have been demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Carvalho-Queiroz¹,

Cook²,

Wang

et al. 2004

Infect Immun

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Schistosoma mansoni, an intravascular parasite, has evolved a number of immune evasion mechanisms to establish itself in the host, such as antioxidant enzymes. Our laboratory has demonstrated that the highest levels of certain antioxidant enzymes are found in adult worms, which are the least susceptible to immune killing. Vaccination of mice with naked DNA constructs containing the gene encoding Cu/Zn cytosolic superoxide dismutase (SmCT-SOD) showed significant levels of protection compared to a control group, and our data demonstrate that the adult worms are a target of the immune response that confers resistance in SmCT-SOD DNA-vaccinated mice. Because SmCT-SOD shows significant identity with the human homologue, we evaluated the reactivity of anti-SmCT-SOD antibodies derived from SmCT-SOD-immunized mice and rabbits and from S. mansoni-infected individuals to human superoxide dismutase (hSOD) and SmCT-SOD parasite-specific peptides to assess the potential for autoimmune responses from immunization with the recombinant molecule. In addition, we evaluated the ability of various SmCT-SOD adjuvant-delivered immunizations to induce cross-reactive antibodies. Both mouse and rabbit antibodies generated against SmCT-SOD recognized the denatured form of hSOD. The same antibodies did not recognize nondenatured hSOD. Sera from infected individuals with different clinical forms of schistosomiasis recognized SmCT-SOD but not hSOD. Antibodies from mice immunized with different SmCT-SOD-containing formulations of both DNA and protein were able to recognize SmCT-SOD-derived peptides but not soluble hSOD. All together, these findings serve as a basis for developing a subunit vaccine against schistosomiasis.Schistosomiasis remains an endemic problem in over 76 countries, although approaches to reduce transmission and morbidity as well as to improve sanitation, mollusciciding and mass chemotherapy, have been attempted (3, 13). Vaccine development to control schistosomiasis is a high priority, as it would offer the potential of cost-efficient, long-lasting prophylaxis (2, 65). Schistosoma mansoni, an intravascular parasite, lives in a hostile environment in close contact with host humoral and cellular cytotoxic factors. Larval parasite killing mechanisms include the release of oxidants by eosinophils, neutrophils, and macrophages potentiated by antibodies and/or cytokines (8,12,16,31,32). However, to establish itself in the host, the parasite has evolved a number of immune evasion mechanisms (17,39,51,60), such as antioxidant enzymes (7,11,30,37). These are essential enzymes involved in the prevention of reactive oxygen species-derived damage. Evidence for the involvement of schistosome antioxidant enzymes, such as cytosolic superoxide dismutase (SmCT-SOD) and glutathione peroxidase (SmGPX), in immune evasion has been presented elsewhere (39). SmCT-SOD and GPX localize to the host-parasite interface (worm tegument and gut epithelium of the adult but not the larval schistosome) (41) and show developmental regulation (29,41,42) wit...

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Section: Discussionmentioning

confidence: 99%

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Carvalho-Queiroz¹,

Cook²,

Wang

et al. 2004

Infect Immun

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“…Also, microparticles or nanoparticles made from biodegradable polymers, such as poly (lactide-co-glycolide) (PLGA), have been investigated for the cytosolic delivery of vaccines. PLGA particles may enable controlled and sustained Ag release (16)(17)(18) and can, as particles in general, deliver large amounts of Ag to APCs at the single-cell level, thereby increasing the probability of reaching MHCI (19)(20)(21)(22)(23).…”

Section: T He Cd8 Ctls Play a Central Role In Fighting Diseasesmentioning

confidence: 99%

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

Bruno

Waeckerle-Men

Håkerud

et al. 2015

The Journal of Immunology

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The generation of CTLs is crucial in the immunological fight against cancer and many infectious diseases. To achieve this, vaccine Ags need to be targeted to the cytosol of dendritic cells, which can activate CD8 T cells via MHC class I (MHCI). Therefore, such targeting has become one of the major objectives of vaccine research. In this study, we aimed to bypass the unwanted and default MHC class II Ag presentation and trigger MHCI presentation by using a photosensitizer that, upon light activation, would facilitate cytosolic targeting of codelivered Ag. Poly(lactide-co-glycolide) microparticles ∼1 μm size were loaded with OVA and the photosensitizer tetraphenyl chlorine disulphonate (TPCS2a) and administered intradermally in mice, which were illuminated 1 d later for activation of the photosensitizer. Immunization in the presence of TPCS2a significantly increased activation of CD8 T cells compared with immunization without TPCS2a and as measured by CD8 T cell proliferation, production of proinflammatory IFN-γ, TNF-α, and IL-2, and prevention of tumor growth. Cytotoxicity was demonstrated by granzyme B production in vitro and by in vivo killing of CFSE-labeled targets. CD4-dependent Ab responses were abrogated in mice immunized with TPCS2a-containing particles, suggesting that photosensitization facilitated a shift from default MHC class II toward MHCI Ag presentation. Hence, vaccine particles with Ag and photosensitizers proved an effective vehicle or adjuvant for stimulation of CTLs, and they may find potential application in therapeutic cancer vaccination and in prophylactic and therapeutic vaccination against intracellular infections.

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“…The protection that microparticles provide to the antigen and the improvement in the uptake by the antigen presenting cells (APC) result in the enhancement of the antigen poor immunogenicity [14]. Besides, the nature of degradation of the carrier maintains a sustained release [15] throughout the time which would be in concordance with a few shot protocol of vaccination.…”

Section: Introductionmentioning

confidence: 99%

Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology

Román

Irache

Gómez

et al. 2008

European Journal of Pharmaceutics and Biopharmaceutics

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Controlled release microparticles for vaccine development

Cited by 143 publications

References 16 publications

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Cross-Reactivity ofSchistosoma mansoniCytosolic Superoxide Dismutase, a Protective Vaccine Candidate, with Host Superoxide Dismutase and Identification of Parasite-Specific B Epitopes

Photosensitizer and Light Pave the Way for Cytosolic Targeting and Generation of Cytosolic CD8 T Cells Using PLGA Vaccine Particles

Co-encapsulation of an antigen and CpG oligonucleotides into PLGA microparticles by TROMS technology

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