A nanoparticle-poly(I:C) combination adjuvant enhances the breadth of the immune response to inactivated influenza virus vaccine in pigs

Sankar Renu, Ninoshkaly Feliciano-Ruiz, Fangjia Lu, Shristi Ghimire, Yi Han, Jennifer Schrock, Santosh Dhakal, Veerupaxagouda Patil, Steven Krakowka, Harm Hogenesch, Gourapura J. Renukaradhya

Research output: Contribution to journalArticle

Abstract

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-α 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 IFNγ 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.

Original languageEnglish (US)
Article number229
JournalVaccines
Volume8
Issue number2
DOIs
StatePublished - Jun 2020
Externally publishedYes

Keywords

  • Intranasal vaccination
  • Mucosal immunity
  • Nano-11
  • Pigs
  • Poly(I:C)
  • Swine influenza virus
  • T and B cell peptides

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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  • Cite this

    Renu, S., Feliciano-Ruiz, N., Lu, F., Ghimire, S., Han, Y., Schrock, J., Dhakal, S., Patil, V., Krakowka, S., Hogenesch, H., & Renukaradhya, G. J. (2020). A nanoparticle-poly(I:C) combination adjuvant enhances the breadth of the immune response to inactivated influenza virus vaccine in pigs. Vaccines, 8(2), [229]. https://doi.org/10.3390/vaccines8020229