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

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

doi:10.3390/vaccines8020229

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.

Highlights

Virulent swine influenza A virus (SwIAV) infection causes acute febrile respiratory disease in pigs of all ages, and is a serious economic burden to the global pork industry [1,2]
The FluSure XP® commercial inactivated swine influenza virus vaccine was purchased from Zoetis (Kalamazoo, MI, USA); it is a multivalent commercial inactivated virus vaccine containing H1N1, H1N2 and H3N2 SwIAVs and an adjuvant
Nano-11 and killed swine influenza virus antigen (KAg) as a Vaccines model antigen (1:1, 2:1, 4:1 and 8:1) to prepare the optimal vaccine formulation based on nanoparticle size, surface and4:1 antigen

Summary

Introduction

Virulent swine influenza A virus (SwIAV) infection causes acute febrile respiratory disease in pigs of all ages, and is a serious economic burden to the global pork industry [1,2]. Vaccines 2020, 8, 229 to influenza virus infection owing to the presence of receptors for both mammalian (swine/human) and avian origin viruses in respiratory epithelial cells [3]. SwIAV spillover to humans is evidence that pigs can act as a mixing vessel for mammalian and avian influenza viruses [2,3]. It is accepted that developing SwIAV-specific cross-reactive immune response in pigs through vaccination is the most convenient and effective method to mitigate disease outbreaks, which will help the swine industry and reduce the public health risk

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