Optimization of a Der p 2-based prophylactic DNA vaccine against house dust mite allergy

Pulsawat, Pinya; Pitakpolrat, Patrawadee; Prompetchara, Eakachai; Kaewamatawong, Theerayuth; Techakriengkrai, Navapon; Sirivichayakul, Sunee; Buranapraditkun, Supranee; Hannaman, Drew; Ruxrungtham, Kiat; Jacquet, Alain

doi:10.1016/j.imlet.2013.01.013

Cited by 20 publications

(18 citation statements)

References 41 publications

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“…Similarly, no significant increase in airway resistance was observed with small PLGA particles when challenged with increasing doses of methacholine. Multiple DNA-based vaccine systems have also reported induction of allergen-specific IgG2a responses and reduced eosinophilia following vaccination (54,55). However, these responses are restricted by the ability of the plasmid DNA constructs to reach a threshold antigen expression after vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…This necessitated the formulation of a vaccine that involved co-administration of the allergen with adjuvants that promote Th1-biased immune responses in order to effectively induce Der p2-specific Th1-type antibodies that would alleviate lung damage associated with exposure to allergen (20,21). Unmethylated cytosinephosphate-guanine motifs-1826 (CpG) is a potent oligodeoxynucleotide used as an adjuvant for polarization of immune responses to the Th1-type (22)(23)(24). It is an agonist to Toll-like receptor-9 which activates DCs and B cells to produce Th1-specific cytokines and suppresses Th2-modulated allergic responses (21).…”

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: Discussionmentioning

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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“…Mice were immunized with DNA constructs by intramuscular in vivo electroporation, IM-EP (Ichor Medical Systems) at the tibialis muscle as previously described [23].…”

Section: Methodsmentioning

confidence: 99%

Induction of Neutralizing Antibody Response against Four Dengue Viruses in Mice by Intramuscular Electroporation of Tetravalent DNA Vaccines

et al. 2014

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DNA vaccine against dengue is an interesting strategy for a prime/boost approach. This study evaluated neutralizing antibody (NAb) induction of a dengue tetravalent DNA (TDNA) vaccine candidate administered by intramuscular-electroporation (IM-EP) and the benefit of homologous TDNA boosting in mice. Consensus humanized pre-membrane (prM) and envelope (E) of each serotypes, based on isolates from year 1962–2003, were separately cloned into a pCMVkan expression vector. ICR mice, five-six per group were immunized for three times (2-week interval) with TDNA at 100 µg (group I; 25 µg/monovalent) or 10 µg (group II; 2.5 µg/monovalent). In group I, mice received an addtional TDNA boosting 13 weeks later. Plaque reduction neutralization tests (PRNT) were performed at 4 weeks post-last immunization. Both 100 µg and 10 µg doses of TDNA induced high NAb levels against all DENV serotypes. The median PRNT50 titers were comparable among four serotypes of DENV after TDNA immunization. Median PRNT50 titers ranged 240–320 in 100 µg and 160–240 in 10 µg groups (p = ns). A time course study of the 100 µg dose of TDNA showed detectable NAb at 2 weeks after the second injection. The NAb peaked at 4 weeks after the third injection then declined over time but remained detectable up to 13 weeks. An additional homologous TDNA boosting significantly enhanced the level of NAb from the nadir for at least ten-fold (p<0.05). Of interest, we have found that the use of more recent dengue viral strain for both vaccine immunogen design and neutralization assays is critical to avoid a mismatching outcome. In summary, this TDNA vaccine candidate induced good neutralizing antibody responses in mice; and the DNA/DNA prime/boost strategy is promising and warranted further evaluation in non-human primates.

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“…Recurrent contact with the respective allergen(s) will preserve and stabilize the initial vaccine-driven response. Even very low doses of DNA 23 , 24 or mRNA 25 vaccines that prime barely detectable immune responses set an adequate immune bias, which is expanded by subsequent (natural) exposure to the allergen, e.g., seasonal aerosol exposure to pollen allergens. This closely resembles to lessons learned about the efficacy of vaccines against infectious diseases: the presence of the pathogen boosts vaccination responses and thus contributes to the maintenance of memory 26 …”

Section: Different Requirements For Prevention Of Infectious Diseasesmentioning

confidence: 99%

Allergens are not pathogens

Weiss

Scheiblhofer

Thalhamer

2013

Human Vaccines & Immunotherapeutics

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Vaccination against infectious diseases has been one of the major breakthroughs in human medical history, saving the lives of millions of people each year. More recently, prophylactic vaccination against non-infectious diseases such as cancer, Alzheimer’s disease, diabetes, and type I allergy is being investigated. Particularly in case of IgE-driven allergic disorders, which afflict almost a quarter of the population in highly developed countries, preventative measures would represent a major improvement for patients’ health as well as an economic relief for public health services. As an alternative to allergen-specific immunotherapy, prophylactic vaccination against type I allergic diseases could slow down or even stop the progress of the allergy pandemic. Allergen-encoding gene-based vaccines, i.e., plasmid DNA and mRNA vaccines, provide the advantage of purity over crude allergen extracts, which involve the risk of de novo sensitizations. Furthermore, these formulations have been demonstrated to induce T helper 1 as well as T regulatory immune responses—a pre-requisite for prophylactic intervention against allergies. However, prophylactic vaccines against environmental allergens strikingly differ from conventional vaccines against infectious diseases or therapeutic approaches concerning the underlying immunological mechanisms.

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Optimization of a Der p 2-based prophylactic DNA vaccine against house dust mite allergy

Cited by 20 publications

References 41 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

Induction of Neutralizing Antibody Response against Four Dengue Viruses in Mice by Intramuscular Electroporation of Tetravalent DNA Vaccines

Allergens are not pathogens

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