Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs

Varun Dwivedi, Cordelia Manickam, Santosh Dhakal, Basavaraj Binjawadagi, Kang Ouyang, Jagadish Hiremath, Mahesh Khatri, Jacquelyn Gervay-Hague, Chang Won Lee, Gourapura J. Renukaradhya

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalVeterinary Microbiology
Volume186
DOIs
StatePublished - Apr 15 2016

Fingerprint

Natural Killer T-Cells
Influenza Vaccines
Adaptive Immunity
Influenza A virus
Innate Immunity
natural killer cells
adjuvants
Swine
vaccines
Ligands
T-lymphocytes
swine
lungs
human influenza
cells
respiratory system
Orthomyxoviridae
cytokines
Lung
cross immunity

Keywords

  • Adjuvant
  • INKT cell
  • Intranasal vaccine
  • Pigs
  • Swine influenza virus
  • α-GalCer

ASJC Scopus subject areas

  • Microbiology
  • veterinary(all)

Cite this

Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs. / Dwivedi, Varun; Manickam, Cordelia; Dhakal, Santosh; Binjawadagi, Basavaraj; Ouyang, Kang; Hiremath, Jagadish; Khatri, Mahesh; Gervay-Hague, Jacquelyn; Lee, Chang Won; Renukaradhya, Gourapura J.

In: Veterinary Microbiology, Vol. 186, 15.04.2016, p. 157-163.

Research output: Contribution to journalArticle

Dwivedi, Varun ; Manickam, Cordelia ; Dhakal, Santosh ; Binjawadagi, Basavaraj ; Ouyang, Kang ; Hiremath, Jagadish ; Khatri, Mahesh ; Gervay-Hague, Jacquelyn ; Lee, Chang Won ; Renukaradhya, Gourapura J. / Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs. In: Veterinary Microbiology. 2016 ; Vol. 186. pp. 157-163.
@article{c0c8c2486ec04f56a7639a0bbec24775,
title = "Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs",
abstract = "Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract.",
keywords = "Adjuvant, INKT cell, Intranasal vaccine, Pigs, Swine influenza virus, α-GalCer",
author = "Varun Dwivedi and Cordelia Manickam and Santosh Dhakal and Basavaraj Binjawadagi and Kang Ouyang and Jagadish Hiremath and Mahesh Khatri and Jacquelyn Gervay-Hague and Lee, {Chang Won} and Renukaradhya, {Gourapura J.}",
year = "2016",
month = "4",
day = "15",
doi = "10.1016/j.vetmic.2016.02.028",
language = "English (US)",
volume = "186",
pages = "157--163",
journal = "Veterinary Microbiology",
issn = "0378-1135",
publisher = "Elsevier",

}

TY - JOUR

T1 - Adjuvant effects of invariant NKT cell ligand potentiates the innate and adaptive immunity to an inactivated H1N1 swine influenza virus vaccine in pigs

AU - Dwivedi, Varun

AU - Manickam, Cordelia

AU - Dhakal, Santosh

AU - Binjawadagi, Basavaraj

AU - Ouyang, Kang

AU - Hiremath, Jagadish

AU - Khatri, Mahesh

AU - Gervay-Hague, Jacquelyn

AU - Lee, Chang Won

AU - Renukaradhya, Gourapura J.

PY - 2016/4/15

Y1 - 2016/4/15

N2 - Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract.

AB - Pigs are considered as the source of some of the emerging human flu viruses. Inactivated swine influenza virus (SwIV) vaccine has been in use in the US swine herds, but it failed to control the flu outbreaks. The main reason has been attributed to lack of induction of strong local mucosal immunity in the respiratory tract. Invariant natural killer T (iNKT) cell is a unique T cell subset, and activation of iNKT cell using its ligand α-Galactosylceramide (α-GalCer) has been shown to potentiate the cross-protective immunity to inactivated influenza virus vaccine candidates in mice. Recently, we discovered iNKT cell in pig and demonstrated its activation using α-GalCer. In this study, we evaluated the efficacy of an inactivated H1N1 SwIV coadministered with α-GalCer intranasally against a homologous viral challenge. Our results demonstrated the potent adjuvant effects of α-GalCer in potentiating both innate and adaptive immune responses to SwIV Ags in the lungs of pigs, which resulted in reduction in the lung viral load by 3 logs compared to without adjuvant. Immunologically, in the lungs of pigs vaccinated with α-GalCer an increased virus specific IgA response, IFN-α secretion and NK cell-cytotoxicity was observed. In addition, iNKT cell-stimulation enhanced the secretion of Th1 cytokines (IFN-γ and IL-12) and reduced the production of immunosuppressive cytokines (IL-10 and TGF-β) in the lungs of pigs⋅ In conclusion, we demonstrated for the first time iNKT cell adjuvant effects in pigs to SwIV Ags through augmenting the innate and adaptive immune responses in the respiratory tract.

KW - Adjuvant

KW - INKT cell

KW - Intranasal vaccine

KW - Pigs

KW - Swine influenza virus

KW - α-GalCer

UR - http://www.scopus.com/inward/record.url?scp=84960110971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84960110971&partnerID=8YFLogxK

U2 - 10.1016/j.vetmic.2016.02.028

DO - 10.1016/j.vetmic.2016.02.028

M3 - Article

VL - 186

SP - 157

EP - 163

JO - Veterinary Microbiology

JF - Veterinary Microbiology

SN - 0378-1135

ER -