A Protective Allergy Vaccine Based on CpG- and Protamine-Containing PLGA Microparticles

Gómez, Julia M. Martínez; Fischer, Stefan; Csaba, Nœmi; Kündig, Thomas M.; Merkle, Hans P.; Gander, Bruno; Johansen, Pål

doi:10.1007/s11095-007-9318-0

Cited by 60 publications

(32 citation statements)

References 44 publications

(31 reference statements)

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“…An alternative co-delivery method is to administer CpG and Der p2 in biodegradable poly(lactic-co-glycolic acid) (PLGA) polymer particles. In addition to co-delivering multiple molecules, many studies have recognized the significance of PLGA particulate vaccines in stimulating robust Th1-type responses as characterized by secretion of IgG2a antibodies (29,30). Vaccination of mice with antigen-loaded PLGA microparticles and CpG, either co-loaded with antigen or injected as a solution, showed enhanced secretion of IgG2a antibodies with a greater ratio of IgG2a:IgG1 antibodies when compared to mice vaccinated with a mixture of antigen and aluminum hydroxide (31).…”

Section: Introductionmentioning

confidence: 99%

“…In addition to co-delivering multiple molecules, many studies have recognized the significance of PLGA particulate vaccines in stimulating robust Th1-type responses as characterized by secretion of IgG2a antibodies (29,30). Vaccination of mice with antigen-loaded PLGA microparticles and CpG, either co-loaded with antigen or injected as a solution, showed enhanced secretion of IgG2a antibodies with a greater ratio of IgG2a:IgG1 antibodies when compared to mice vaccinated with a mixture of antigen and aluminum hydroxide (31). We have previously reported that PLGA particles encapsulating antigen and CpG can stimulate robust immune responses compared to vaccination of antigen and CpG in solution (32,33).…”

Section: Introductionmentioning

confidence: 99%

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Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Joshi

Adamcakova‐Dodd

Jing

et al. 2014

AAPS J

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Abstract. Poly(lactic-co-glycolic acid) (PLGA) particles carrying antigen and adjuvant is a promising vaccine system which has been shown to stimulate systemic antigen-specific immune responses. In this study, we investigated the relationship of (i) the sizes of PLGA particle and (ii) the presence of cytosinephosphate-guanine motifs (CpG), with the extent and type of immune response stimulated against Dermatophagoides pteronyssinus-2 (Der p2) antigen. Different sizes of PLGA particles encapsulating CpG were prepared using a double emulsion solvent evaporation method. Mice were vaccinated with Der p2 and different sizes of empty or CpG-loaded PLGA particles. Vaccinated mice were exposed to daily intranasal instillation of Der p2 for 10 days followed by euthanization to estimate leukocyte accumulation in bronchoalveolar lavage (BAL) fluids, antibody profiles, and airway hyperresponsiveness. PLGA particles showed a size-dependent decrease in the proportion of eosinophils found in BAL fluids. Mice vaccinated with the Der p2 coated on 9-μm-sized empty PLGA particles showed increased levels of IgE and IgG1 antibodies as well as increased airway hyperresponsiveness. All sizes of PLGA particles encapsulating CpG prevented airway hyperresponsiveness after Der p2 exposures. Inflammatory responses to Der p2 exposure were significantly reduced when smaller PLGA particles were used for vaccination. In addition, encapsulating CpG in PLGA particles increased IgG2a secretion. This study shows that the size of PLGA particles used for vaccination plays a major role in the prevention of house dust mite-induced allergy and that incorporation of CpG into the PLGA particles preferentially develops a Th1-type immune response.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Joshi

Adamcakova‐Dodd

Jing

et al. 2014

AAPS J

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“…Therefore, there is a high interest in improving current methods of SIT. Numerous studies have investigated new strategies to optimise the allergen molecules [3,4,5], the adjuvants used [6,7,8], the dosage form [9,10,11], as well as the route of allergen administration [12,13,14]. …”

Section: Introductionmentioning

confidence: 99%

Intralymphatic Injections as a New Administration Route for Allergen-Specific Immunotherapy

Martínez-Gómez

Johansen

Erdmann

et al. 2009

Int Arch Allergy Immunol

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Background: IgE-mediated allergy can be treated by subcutaneous allergen-specific immunotherapy (SIT). However, the percentage of allergic patients undergoing SIT is low, mainly due to the long duration of the therapy and the risk of severe systemic allergic reactions associated with the allergen administration. To improve the safety and attractiveness of SIT for patients, alternative routes of allergen administration are being explored, such as sub-lingual or oral administration. Methods: The present study evaluated direct intralymphatic allergen administration as a means to enhance SIT with bee venom and cat fur allergens in mice. Allergen-specific antibody and T-cell responses were analysed by ELISA and flow cytometry. The therapeutic potential of intralymphatic immunisation in sensitised mice was analysed using an anaphylaxis model. Results: Direct injection of the major bee venom allergen phospholipase A₂ or the major cat fur allergen Fel d 1 into inguinal lymph nodes enhanced allergen-specific IgG and T-cell responses when compared with subcutaneous injections. Moreover, only intralymphatic immunisation stimulated the production of the Th1-dependent subclass IgG2a, which is associated with improved protection against allergen-induced anaphylaxis. Biodistribution studies showed that injection into the lymph node delivered antigen more efficiently to subcutaneous lymph nodes than subcutaneous injection. Conclusions: As intralymphatic immunisation induced more than 10-fold higher IgG2a responses with 100-fold lower allergen doses than subcutaneous immunisation, this approach should allow to reduce both the number of allergen injections as well as the allergen dose, improving both efficacy and safety of SIT.

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“…The effect of the CpG nucleotide was further strengthened when protamine was co-encapsulated for the complexation of CpG. 76 Chitosan has been used for its mucoadhesiveness that makes this particle attractive for mucosal immunity. 43 Following this line of evidence, Liu et al tested the immunotherapeutic efficiency of the IN administration of Dermatophagoides farinae extract (Der f) entrapped in chitosan microparticles.…”

Section: Arthropoda Allergensmentioning

confidence: 99%

Nanoparticle–allergen complexes for allergen immunotherapy

Felice¹,

Colombo²

2017

IJN

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Allergen-specific immunotherapy was introduced in clinical settings more than 100 years ago. It remains the only curative approach to treating allergic disorders that ameliorates symptoms, reduces medication costs, and blocks the onset of new sensitizations. Despite this clinical evidence and knowledge of some immunological mechanisms, there remain some open questions regarding the safety and efficacy of this treatment. This suggests the need for novel therapeutic approaches that attempt to reduce the dose and frequency of treatment administration, improving patient compliance, and reducing costs. In this context, the use of novel adjuvants has been proposed and, in recent years, biomedical applications using nanoparticles have been exploited in the attempt to find formulations with improved stability, bioavailability, favorable biodistribution profiles, and the capability of targeting specific cell populations. In this article, we review some of the most relevant regulatory aspects and challenges concerning nanoparticle-based formulations with immunomodulatory potential, their related immunosafety issues, and the nature of the nanoparticles most widely employed in the allergy field. Furthermore, we report in vitro and in vivo data published using allergen/nanoparticle systems, discuss their impact on the immune system in terms of immunomodulatory activity and the reduction of side effects, and show that this strategy is a novel and promising tool for the development of allergy vaccines.

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A Protective Allergy Vaccine Based on CpG- and Protamine-Containing PLGA Microparticles

Abstract: This study shows that allergen-specific immunotherapy with a PLGA-based allergen-delivery system in combination with CpG enhanced the induction of protective IgG2a immune responses. This may improve SIT compliance and shorten its duration.

Cited by 60 publications

References 44 publications

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Intralymphatic Injections as a New Administration Route for Allergen-Specific Immunotherapy

Nanoparticle–allergen complexes for allergen immunotherapy

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A Protective Allergy Vaccine Based on CpG- and Protamine-Containing PLGA Microparticles

Abstract: This study shows that allergen-specific immunotherapy with a PLGA-based allergen-delivery system in combination with CpG enhanced the induction of protective IgG2a immune responses. This may improve SIT compliance and shorten its duration.

Cited by 60 publications

References 44 publications

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Intralymphatic Injections as a New Administration Route for Allergen-Specific Immunotherapy

Nanoparticle&ndash;allergen complexes for allergen immunotherapy

Contact Info

Product

Resources

About

Nanoparticle–allergen complexes for allergen immunotherapy