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1.
Int J Pharm ; 662: 124479, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39019298

RESUMO

BACKGROUND: Animal models for food allergies serve as crucial tools in understanding allergy mechanisms and assessing the efficacy of potential desensitization methods. The effectiveness of inducing allergies in mice through intragastric lavage sensitization varies. The intraperitoneal method can trigger systemic anaphylaxis, however it lacks anatomical relevance. Hence, a uniform and reliable allergy induction method in mice is required. Tape -stripping can mimic atopic dermatitis (AD), a precursor to lifelong peanut allergies in humans. Furthermore, skin damage triggers the upregulation of skin alarmins and the expansion of small-intestinal mast cells, both implicated in allergy development. METHODS: We standardized a skin-based sensitization method in a mouse model of peanut allergy using skin tape-stripping followed by allergen application. We compared this method with intragastric sensitization. RESULTS: Skin-based sensitization led to increased mast cells, goblet cells, and eosinophils in the small intestine, elevated systemic IgE levels, murine mast cell protease-1 (mMCP-1), histamine, and eosinophilic activity in peripheral blood. Moreover, it resulted in a significant hypothermic response, with nearly 30% mortality following an oral challenge one-month post-sensitization. CONCLUSION: Our research offers a standardized and readily reproducible method for inducing peanut allergy in mice, which could also be adapted for other food allergens.


Assuntos
Alérgenos , Quimases , Modelos Animais de Doenças , Imunoglobulina E , Mastócitos , Hipersensibilidade a Amendoim , Pele , Animais , Hipersensibilidade a Amendoim/imunologia , Camundongos , Pele/imunologia , Pele/metabolismo , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mastócitos/imunologia , Alérgenos/imunologia , Alérgenos/administração & dosagem , Feminino , Camundongos Endogâmicos BALB C , Dermatite Atópica/imunologia , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Eosinófilos/imunologia , Histamina
2.
ACS Infect Dis ; 10(5): 1552-1560, 2024 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-38623820

RESUMO

Tyrosine cross-linking has recently been used to produce nanoclusters (NCs) from peptides to enhance their immunogenicity. In this study, NCs were generated using the ectodomain of the ion channel Matrix 2 (M2e) protein, a conserved influenza surface antigen. The NCs were administered via intranasal (IN) or intramuscular (IM) routes in a mouse model in a prime-boost regimen in the presence of the adjuvant CpG. After boost, a significant increase in anti-M2e IgG and its subtypes was observed in the serum and lungs of mice vaccinated through the IM and IN routes; however, significant enhancement in anti-M2e IgA in lungs was observed only in the IN group. Analysis of cytokine concentrations in stimulated splenocyte cultures indicated a Th1/Th17-biased response. Mice were challenged with a lethal dose of A/California/07/2009 (H1N1pdm), A/Puerto Rico/08/1934 (H1N1), or A/Hong Kong/08/1968 (H3N2) strains. Mice that received M2e NCs + CpG were significantly protected against these strains and showed decreased lung viral titers compared with the naive mice and M2e NC-alone groups. The IN-vaccinated group showed superior protection against the H3N2 strain as compared to the IM group. This research extends our earlier efforts involving the tyrosine-based cross-linking method and highlights the potential of this technology in enhancing the immunogenicity of short peptide immunogens.


Assuntos
Anticorpos Antivirais , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Tirosina , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Camundongos , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Tirosina/química , Tirosina/farmacologia , Vírus da Influenza A Subtipo H1N1/imunologia , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/genética , Camundongos Endogâmicos BALB C , Vírus da Influenza A Subtipo H3N2/imunologia , Adjuvantes Imunológicos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Pulmão/virologia , Pulmão/imunologia , Administração Intranasal , Injeções Intramusculares , Citocinas , Proteção Cruzada , Proteínas Viroporinas
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