α-Galactosylceramide protects swine against influenza infection when administered as a vaccine adjuvant.

Bianca L Artiaga,John A Lednicky,Timothy J Hackmann,Shahram Salek-Ardakani,Guan Yang,William L Castleman,John P Driver,Jürgen A Richt,Qinfang Liu

doi:10.1038/srep23593

Bianca L Artiaga, John A Lednicky + Show 7 more

Open Access

https://doi.org/10.1038/srep23593

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Abstract

Natural killer T (NKT) -cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide array of immune responses with many promising immunotherapeutic applications, including the enhancement of vaccines against infectious diseases and cancer. In the current study, we evaluated whether α-GalCer generates protective immunity against a swine influenza (SI) virus infection when applied as an intramuscular vaccine adjuvant. Immunization of newly weaned piglets with UV-killed pandemic H1N1 A/California/04/2009 (kCA04) SI virus and α-GalCer induced high titers of anti-hemagglutinin antibodies and generated virus-specific T cells that localized in intrapulmonary airways and in alveolar walls. Vaccination with α-GalCer resulted in a systemic increase in NKT-cell concentrations, including in the respiratory tract, which was associated with complete inhibition of viral replication in the upper and lower respiratory tract and much reduced viral shedding. These results indicate that NKT-cell agonists could be used to improve swine vaccine formulations in order to reduce the clinical signs of SI infection and limit the spread of influenza viruses amongst commercial pigs.

Highlights

Mock/Mock); mock vaccinated and CA04 challenged (Group 2; Mock/CA04), killed CA04 (kCA04) vaccinated and CA04 challenged (Group 3; kCA04/CA04); α -GalCer+ kCA04 vaccinated and CA04 challenged (Group 4; α GC+ kCA04/CA04)
To investigate whether co-immunization with α -GalCer and inactivated CA04 virus protects swine from Swine influenza (SI) virus infection when injected into the neck muscle, where most swine vaccines are delivered, 3-week-old piglets were vaccinated with 106 TCID50 UV-killed CA04 alone or with 100 μg/kg α -GalCer, or mock vaccinated with virus-free media
We demonstrate that α -GalCer co-immunized with inactivated CA04 into the neck muscle of piglets generated protective immunity against homologous influenza infection, indicating that natural killer T (NKT)-cell agonists could be used to improve swine vaccine formulations in order to reduce the clinical signs of SI infection and limit the spread of influenza viruses among commercial pigs

Summary

Introduction

Mock/Mock); mock vaccinated and CA04 challenged (Group 2; Mock/CA04), kCA04 vaccinated and CA04 challenged (Group 3; kCA04/CA04); α -GalCer+ kCA04 vaccinated and CA04 challenged (Group 4; α GC+ kCA04/CA04). The glycolipid antigen most studied for this purpose is α -galactosylceramide (α -GalCer) It potently stimulates NKT-cells to release large quantities of cytokines that induce the trans-activation of a wide array of bystander cells including NK cells, DCs, and conventional T cells subsets [reviewed in19]. These NKT-cell-mediated responses boost the efficacy of influenza vaccines resulting in strong protection against lethal challenges with H1N1 or H3N2 virus strains in mouse models[20,21,22,23,24]. These results indicate a potential veterinary use for NKT-cell adjuvants for protecting commercial swine from influenza viruses and other important pathogens

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