Use of immunostimulatory liposome‐nucleic acid complexes in allergen‐specific immunotherapy of dogs with refractory atopic dermatitis – a pilot study

Mueller, Ralf S.; Veir, Julia K.; Fieseler, Kathryn V.; Dow, Steven

doi:10.1111/j.1365-3164.2005.00426.x

Cited by 52 publications

(49 citation statements)

References 31 publications

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“…Other applications of the adjuvant platform include mucosal immunization, where we have found that the liposome-TLR agonist adjuvants are effective (S. Dow, unpublished data). The LANAC adjuvants may also be useful clinically, because we showed recently that vaccination of pet dogs with refractory atopic dermatitis with allergens complexed to LANAC adjuvants was effective in reducing clinical signs and reversing some Th2 abnormalities (71). Therefore, the liposome-TLR agonist adjuvant system described in this study may be a useful addition to the list of currently available vaccine adjuvants capable of eliciting strong T cell responses against protein and peptide Ags.…”

Section: Discussionmentioning

confidence: 98%

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Zaks

Jordan

Guth³

et al. 2006

The Journal of Immunology

227

187

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Complexing TLR9 agonists such as plasmid DNA to cationic liposomes markedly potentiates their ability to activate innate immunity. We therefore reasoned that liposomes complexed with DNA or other TLR agonists could be used as effective vaccine adjuvants. To test this hypothesis, the vaccine adjuvant effects of liposomes complexed to TLR agonists were assessed in mice. We found that liposomes complexed to nucleic acids (liposome-Ag-nucleic acid complexes; LANAC) were particularly effective adjuvants for eliciting CD4+ and CD8+ T cell responses against peptide and protein Ags. Notably, LANAC containing TLR3 or TLR9 agonists effectively cross-primed CD8+ T cell responses against even low doses of protein Ags, and this effect was independent of CD4+ T cell help. Ag-specific CD8+ T cells elicited by LANAC adjuvants were functionally active and persisted for long periods of time in tissues. In a therapeutic tumor vaccine model, immunization with the melanoma peptide trp2 and LANAC adjuvant controlled the growth of established B16 melanoma tumors. In a prophylactic vaccine model, immunization with the Mycobacterium tuberculosis protein ESAT-6 with LANAC adjuvant elicited significant protective immunity against aerosol challenge with virulent M. tuberculosis. These results suggest that certain TLR agonists can be combined with cationic liposomes to produce uniquely effective vaccine adjuvants capable of eliciting strong T cell responses against protein and peptide Ags.

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Section: Discussionmentioning

confidence: 98%

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Zaks

Jordan

Guth³

et al. 2006

The Journal of Immunology

227

187

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“…In other studies in which CpGs were deployed, for example in a study on asthma in humans,20 and a study on dogs with atopic dermatitis,21 CpGs were used as adjuvants for an allergen‐specific immunotherapy or as vaccine adjuvants for increased effectiveness of the human hepatitis B11 and the equine influenza and Rhodococcus equi vaccines 22, 23, 24, 25. In these studies, the CpGs induced a strong Th1 cell‐mediated and humoral immune response 11.…”

Section: Discussionmentioning

confidence: 99%

“…As an adjuvant, CpG‐ODN has been successfully used both in a human phase I and IIa in vivo asthma study with the house dust mite allergen as well as in a study of atopic dogs with specific allergens as an allergen‐specific immunotherapy 20, 21. CpG‐ODN also has been applied as an adjuvant in in vitro and in vivo vaccination studies 22, 23, 24, 25.…”

mentioning

confidence: 99%

Nanoparticulate CpG Immunotherapy in RAO‐Affected Horses: Phase I and IIa Study

Klier

Lehmann

Fuchs

et al. 2015

Veterinary Internal Medicne

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BackgroundRecurrent airway obstruction (RAO), an asthma‐like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine‐phosphate‐guanosine‐oligodeoxynucleotides (CpG‐ODN) are known to direct the immune system toward a Th1‐pathway, and away from the pro‐allergic Th2‐line (Th2/Th1‐shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG‐ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP‐bound CpG‐ODN in RAO‐affected horses have shown promising results.ObjectivesThe aim of this study was to evaluate the clinical and immunological effects of GNP‐bound CpG‐ODN in a double‐blinded, placebo‐controlled, prospective, randomized clinical trial and to verify a sustained effect post‐treatment.Animals and MethodsTwenty‐four RAO‐affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post‐treatment (III).ResultsAt time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO 2 and neutrophil percentage, and an increase in arterial oxygen pressure.Conclusion and Clinical ImportanceAdministration of a GNP‐bound CpG‐ODN formulation caused a potent and persistent effect on allergic and inflammatory‐induced clinical variables in RAO‐affected horses. This treatment, therefore, provides an innovative, promising, and well‐tolerated strategy beyond conventional symptomatic long‐term therapy and could serve as a model for asthma treatment in humans.

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“…22 In addition, we also reported that LDC could be used as a vaccine adjuvant for immunization of dogs with refractory atopic dermatitis and that immunization with the LDC-based vaccine could reduce clinical signs and suppress the Th2 polarization of the T cells from atopic dogs. 23 In addition, we showed recently that in cancer-bearing dogs, the LDC adjuvant could be used recently to elicit humoral immune responses even in dogs receiving chemotherapy. 24 Others have also reported that liposomes complexed with DNA can be used to produce effective vaccine adjuvants.…”

mentioning

confidence: 99%

Evaluation of a Novel Tumor Vaccine in Dogs with Hemangiosarcoma

U'Ren

Biller

Elmslie³

et al. 2007

Veterinary Internal Medicne

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Background: Hemangiosarcoma (HSA) is a highly metastatic and often rapidly fatal tumor of dogs. At present, adjuvant chemotherapy is the only proven effective treatment for dogs with HSA, though the benefits from chemotherapy are modest. Administration of immunotherapy together with chemotherapy has also been reported to improve survival in dogs with HSA. Therefore, we evaluated safety and immunologic responses to a novel tumor vaccine administered together with doxorubicin chemotherapy in dogs with different stages of HSA.Hypothesis: That tumor vaccination could be safely and effectively combined with doxorubicin chemotherapy for treatment of dogs with HSA.Animals: Twenty-eight dogs with various stages of HSA were enrolled in the study. Methods: The HSA vaccine was prepared with lysates of allogeneic canine HSA cell lines mixed with an adjuvant composed of liposome-DNA complexes. Dogs received a series of 8 immunizations administered over a 22-week period, and most also received chemotherapy. Clinical adverse effects were noted, immune responses were measured by enzyme-linked immunosorbent assay (ELISA) and flow cytometry, and survival times were calculated.Results: The most common adverse effects observed in vaccinated dogs also treated with doxorubicin chemotherapy were diarrhea and anorexia. Vaccinated dogs were found to mount strong humoral immune responses against a control antigen and, most dogs also mounted antibody responses against canine HSA cells. Thirteen dogs with stage II splenic HSA that received the tumor vaccine plus doxorubicin chemotherapy had an overall median survival time of 182 days.Conclusions: We conclude that an allogeneic tumor lysate vaccine is safe in dogs with HSA and can elicit humoral immune responses in dogs that are receiving concurrent doxorubicin chemotherapy.

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Use of immunostimulatory liposome‐nucleic acid complexes in allergen‐specific immunotherapy of dogs with refractory atopic dermatitis – a pilot study

Cited by 52 publications

References 31 publications

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Efficient Immunization and Cross-Priming by Vaccine Adjuvants Containing TLR3 or TLR9 Agonists Complexed to Cationic Liposomes

Nanoparticulate CpG Immunotherapy in RAO‐Affected Horses: Phase I and IIa Study

Evaluation of a Novel Tumor Vaccine in Dogs with Hemangiosarcoma

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