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Int J Nanomedicine ; 13: 6699-6715, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30425484

RESUMO

BACKGROUND: Influenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses. METHODS: In the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model. Furthermore, we used monosodium urate (MSU) crystals as an adjuvant and co-administered the vaccine formulation as an intranasal mist to flu-free nursery pigs, twice at 3-week intervals. RESULTS: Liposome peptides flu vaccine delivered with MSU adjuvant improved the hemagglutination inhibition antibody titer and mucosal IgA response against the SwIAV challenge and also against two other highly genetically variant IAVs. Liposomal vaccines also enhanced the frequency of peptides and virus-specific T-helper/memory cells and IFN-γ response. The improved specific cellular and mucosal humoral immune responses in adjuvanted liposomal peptides flu vaccine partially protected pigs from flu-induced fever and pneumonic lesions, and reduced the nasal virus shedding and viral load in the lungs. CONCLUSION: Overall, our study shows great promise for using liposome and MSU adjuvant- based subunit flu vaccine through the intranasal route, and provides scope for future, pre-clinical investigations in a pig model for developing potent human intranasal subunit flu vaccines.


Assuntos
Adjuvantes Imunológicos/farmacologia , Imunidade , Vacinas contra Influenza/imunologia , Nanopartículas/química , Infecções por Orthomyxoviridae/imunologia , Peptídeos/imunologia , Ácido Úrico/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Sequência de Aminoácidos , Animais , Formação de Anticorpos/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Citocinas/biossíntese , Cães , Imunidade/efeitos dos fármacos , Imunidade nas Mucosas/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1 , Lipossomos , Pulmão/patologia , Pulmão/virologia , Células Madin Darby de Rim Canino , Nanopartículas/ultraestrutura , Infecções por Orthomyxoviridae/virologia , Peptídeos/química , Sus scrofa , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Vacinação , Carga Viral/efeitos dos fármacos
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