A Nanoparticle-Poly(I:C) Combination Adjuvant Enhances the Breadth of the Immune Response to Inactivated Influenza Virus Vaccine in Pigs

被引:27
作者
Renu, Sankar [1 ,2 ]
Feliciano-Ruiz, Ninoshkaly [1 ,2 ]
Lu, Fangjia [3 ]
Ghimire, Shristi [1 ,2 ]
Han, Yi [1 ,2 ]
Schrock, Jennifer [1 ,2 ]
Dhakal, Santosh [1 ,2 ]
Patil, Veerupaxagouda [1 ,2 ]
Krakowka, Steven [4 ]
HogenEsch, Harm [3 ]
Renukaradhya, Gourapura J. [1 ,2 ]
机构
[1] Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, 1680 Madison Ave, Wooster, OH 44691 USA
[2] Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, Columbus, OH 43210 USA
[3] Purdue Univ, Coll Vet Med, W Lafayette, IN 47907 USA
[4] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA
关键词
Nano-11; swine influenza virus; T and B cell peptides; poly(I:C); intranasal vaccination; mucosal immunity; pigs; SALMONELLA SUBUNIT NANOVACCINE; DENDRITIC CELLS; LYMPHOID-TISSUE; PROTECTION; INFECTION; DELIVERY; IGA;
D O I
10.3390/vaccines8020229
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Intranasal vaccination elicits secretory IgA (SIgA) antibodies in the airways, which is required for cross-protection against influenza. To enhance the breadth of immunity induced by a killed swine influenza virus antigen (KAg) or conserved T cell and B cell peptides, we adsorbed the antigens together with the TLR3 agonist poly(I:C) electrostatically onto cationic alpha-D-glucan nanoparticles (Nano-11) resulting in Nano-11-KAg-poly(I:C) and Nano-11-peptides-poly(I:C) vaccines. In vitro, increased TNF-alpha and IL-1ss cytokine mRNA expression was observed in Nano-11-KAg-poly(I:C)-treated porcine monocyte-derived dendritic cells. Nano-11-KAg-poly(I:C), but not Nano-11-peptides-poly(I:C), delivered intranasally in pigs induced high levels of cross-reactive virus-specific SIgA antibodies secretion in the nasal passage and lungs compared to a multivalent commercial influenza virus vaccine administered intramuscularly. The commercial and Nano-11-KAg-poly(I:C) vaccinations increased the frequency of IFN gamma secreting T cells. The poly(I:C) adjuvanted Nano-11-based vaccines increased various cytokine mRNA expressions in lymph nodes compared to the commercial vaccine. In addition, Nano-11-KAg-poly(I:C) vaccine elicited high levels of virus neutralizing antibodies in bronchoalveolar lavage fluid. Microscopic lung lesions and challenge virus load were partially reduced in poly(I:C) adjuvanted Nano-11 and commercial influenza vaccinates. In conclusion, compared to our earlier study with Nano-11-KAg vaccine, addition of poly(I:C) to the formulation improved cross-protective antibody and cytokine response.
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页数:16
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