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; Hague, Jacquelyn Gervay; Lee, Chang Won; Renukaradhya, Gourapura J.

doi:10.1016/j.vetmic.2016.02.028

Cited by 24 publications

(19 citation statements)

References 28 publications

(40 reference statements)

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“…The addition of exogenous cytokines was not required to expand pig iNKT cells, which is consistent with a previous report (23). iNKT cells were identified using anti-porcine CD3ε Ab and mCD1d tetramer loaded with the a-GalCer analogue PBS57, which cross-reacts with the porcine invariant TCR (22,24,25,(32)(33)(34)(35). iNKT cells and Tconv were, respectively, distinguished as CD3ε + CD1d tetramer + and CD3ε + CD1d tetramer 2 cells.…”

Section: Enrichment Of Inkt Cells From Pig Peripheral Bloodsupporting

confidence: 89%

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Next Generation Sequencing of the Pig αβ TCR Repertoire Identifies the Porcine Invariant NKT Cell Receptor

Yang

Artiaga

Lomelino

et al. 2019

The Journal of Immunology

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Swine represent the only livestock with an established invariant NKT (iNKT) cell-CD1d system. In this study, we exploited the fact that pig iNKT cells can be purified using a mouse CD1d tetramer reagent to establish their TCR repertoire by next generation sequencing. CD1d tetramer-positive pig cells predominantly expressed an invariant Va-Ja rearrangement, without nontemplate nucleotide diversity, homologous to the Va24-Ja18 and Va14-Ja18 rearrangements of human and murine iNKT cells. The coexpressed b-chain used a Vb segment homologous to the semivariant Vb11 and Vb8.2 segments of human and murine iNKT cell receptors. Molecular modeling found that contacts within CD1d and CDR1a that underlie fine specificity differences between mouse and human iNKT cells are conserved between pigs and humans, indicating that the response of porcine and human iNKT cells to CD1d-restricted Ags may be similar. Accordingly, pigs, which are an important species for diverse fields of biomedical research, may be useful for developing human-based iNKT cell therapies for cancer, infectious diseases, and other disorders. Our study also sequenced the expressed TCR repertoire of conventional porcine ab T cells, which identified 48 Va, 50 Ja, 18 Vb, and 18 Jb sequences, most of which correspond to human gene segments. These findings provide information on the ab TCR usage of pigs, which is understudied and deserves further attention.

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Section: Enrichment Of Inkt Cells From Pig Peripheral Bloodsupporting

confidence: 89%

“…Thus, pigs may be useful for determining the efficacy of various glycolipid ligands for human use. There is also potential to use iNKT cell agonists for veterinary applications, including as vaccine adjuvants and antimicrobial agents, which has recently been explored in swine with encouraging results (25,(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

Next Generation Sequencing of the Pig αβ TCR Repertoire Identifies the Porcine Invariant NKT Cell Receptor

Yang

Artiaga

Lomelino

et al. 2019

The Journal of Immunology

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“…36,37 Cytokine ELISA IL-6, IL-10, IL-12, and IFN-γ cytokine secretion in the BAL fluid samples were analyzed by ELISA as described previously. 39…”

Section: Re-stimulation Of Mncs For Flow Cytometry and Supernatant Fomentioning

confidence: 99%

Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs

Dhakal¹,

Cheng²,

Salcido³

et al. 2018

IJN

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BackgroundInfluenza (flu) is a constant threat to humans and animals, and vaccination is one of the most effective ways to mitigate the disease. Due to incomplete protection induced by current flu vaccines, development of novel flu vaccine candidates is warranted to achieve greater efficacy against constantly evolving flu viruses.MethodsIn the present study, we used liposome nanoparticle (<200 nm diameter)-based subunit flu vaccine containing ten encapsulated highly conserved B and T cell epitope peptides to induce protective immune response against a zoonotic swine influenza A virus (SwIAV) H1N1 challenge infection in a pig model. Furthermore, we used monosodium urate (MSU) crystals as an adjuvant and co-administered the vaccine formulation as an intranasal mist to flu-free nursery pigs, twice at 3-week intervals.ResultsLiposome peptides flu vaccine delivered with MSU adjuvant improved the hemagglutination inhibition antibody titer and mucosal IgA response against the SwIAV challenge and also against two other highly genetically variant IAVs. Liposomal vaccines also enhanced the frequency of peptides and virus-specific T-helper/memory cells and IFN-γ response. The improved specific cellular and mucosal humoral immune responses in adjuvanted liposomal peptides flu vaccine partially protected pigs from flu-induced fever and pneumonic lesions, and reduced the nasal virus shedding and viral load in the lungs.ConclusionOverall, our study shows great promise for using liposome and MSU adjuvant- based subunit flu vaccine through the intranasal route, and provides scope for future, pre-clinical investigations in a pig model for developing potent human intranasal subunit flu vaccines.

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“…In contrast, mice express two copies of CD1d, but lack the other CD1 genes [ 54 ]. Porcine CD1d is highly homologous to mouse and human CD1d to the extent that fluorescently labeled mouse or human tetramers loaded with α-GalCer analogs can be used with equal efficiency to visualize pig iNKT cells by flow cytometry [ 19 , 51 , 55 , 56 , 57 , 58 , 59 ]. We have used this tool to show that the prevalence and distribution of iNKT cells among outbred pigs is more like humans than like mice, with the frequency of iNKT cells in blood, spleen, lung, liver, bronchoalveolar lavage fluid (BALF), tracheobronchial lymph node (TBLN), cervical lymph nodes (CLN), and mesenteric lymph nodes (MLN) typically between 0.01% and 1% of total lymphocytes [ 19 , 60 ].…”

Section: Current Understanding Of the Porcine Inkt Cell–cd1d Systementioning

confidence: 99%

“…However, Dwivedi et al demonstrated that α-GalCer also potentiates influenza immunity via the intranasal route. α-GalCer co-administered with a UV-inactivated H1N1 (Sw/OH/24366/07, SwIV OH07) enhanced virus-specific IgA secretion, NK cell cytotoxicity, and Th1 cytokine (IFNγ and IL-12) secretion, and reduced immunosuppressive cytokine (IL-10 and TGF-β) production in the lungs after homologous challenge [ 56 ]. This was associated with a 3-log reduction of viral load in the lungs.…”

Section: Use Of Inkt Cell Agonists As Adjuvants In Swinementioning

confidence: 99%

Harnessing Invariant NKT Cells to Improve Influenza Vaccines: A Pig Perspective

Yang

Richt

Driver

2017

IJMS

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Invariant natural killer T (iNKT) cells are an “innate-like” T cell lineage that recognize glycolipid rather than peptide antigens by their semi-invariant T cell receptors. Because iNKT cells can stimulate an extensive array of immune responses, there is considerable interest in targeting these cells to enhance human vaccines against a wide range of microbial pathogens. However, long overlooked is the potential to harness iNKT cell antigens as vaccine adjuvants for domestic animal species that express the iNKT cell–CD1d system. In this review, we discuss the prospect of targeting porcine iNKT cells as a strategy to enhance the efficiency of swine influenza vaccines. In addition, we compare the phenotype and tissue distribution of porcine iNKT cells. Finally, we discuss the challenges that must be overcome before iNKT cell agonists can be contemplated for veterinary use in livestock.

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

Cited by 24 publications

References 28 publications

Next Generation Sequencing of the Pig αβ TCR Repertoire Identifies the Porcine Invariant NKT Cell Receptor

Next Generation Sequencing of the Pig αβ TCR Repertoire Identifies the Porcine Invariant NKT Cell Receptor

Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs

Harnessing Invariant NKT Cells to Improve Influenza Vaccines: A Pig Perspective

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