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Innate immune responses to a saponin adjuvant in the pig

application of gene expression profiling

Ahlberg, Viktor (2016). Innate immune responses to a saponin adjuvant in the pig. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2016:108
ISBN 978-91-576-8719-7
eISBN 978-91-576-8720-3
[Doctoral thesis]

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Abstract

Vaccination is one of the most powerful ways to prevent infectious diseases. Successful vaccines produce a long-term immunity including effector T and B lymphocytes. In this context, adjuvants have a key role in vaccines by stimulating the innate immunity and thereby enhancing and shaping the subsequent adaptive immune response. The aim of this thesis was to elucidate the early innate immune response to the saponin-based adjuvant Matrix-M in the pig. Gene expression profiling was applied to monitor the global transcriptional response to Matrix-M in vivo. The innate immune response was further characterized by quantitative PCR analysis in vivo and in vitro and the early immunomodulatory effect of Matrix-M was evaluated in a contact exposure model. A mild inflammation and a cellular influx were recorded at the injection site and in the draining lymph node 24 hours after intramuscular injection of Matrix-M in pigs. In accordance, microarray analysis detected transcriptional alterations of genes for cytokines, chemokines and pattern recognition receptors in both tissues. Interferon- regulated genes were significantly overrepresented in these tissues, accompanied by increased gene expression for interferon-β in in the draining lymph node and interferon-α in blood. Transcriptional responses to Matrix-M in vitro were generally low but increased culture and exposure time affected genes for pro-inflammatory cytokines and TH cytokines in lymphocytes. Low levels of interferon-α gene expression were also detected in monocyte-derived dendritic cells. A contact exposure model was established to mimic field conditions when allocating grower pigs, by mixing pigs of various health statuses. After transport and mixing with conventionally reared pigs, all specific pathogen free (SPF) pigs in this model developed respiratory disease. Systemic symptoms that correlated with granulocyte counts, serum amyloid A levels and transcription of IL18 and TLR2 were provoked in two out of four SPF pigs that received saline prior to exposure, but not in those given Matrix-M. Taken together, the application of gene expression profiling successfully identified the induction of innate immune responses in porcine tissues and indicated that Matrix-M primes the host for further immune regulation. Thus, Matrix-M or similar saponin formulations are potentially useful clinical immunomodulators or adjuvants in emergency vaccines.

Authors/Creators:Ahlberg, Viktor
Title:Innate immune responses to a saponin adjuvant in the pig
Subtitle:application of gene expression profiling
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2016
Depositing date:3 October 2016
Volume:2016:108
Number of Pages:81
Papers/manuscripts:
NumberReferences
IAndersson, M., Ahlberg, V., Jensen-Waern, M. & Fossum, C. (2011). Intestinal gene expression in pigs experimentally co-infected with PCV2 and PPV. Veterinary Immunology and Immunopathology, 142(1-2), pp. 72- 80.
IIAhlberg, V., Lövgren Bengtsson, K., Wallgren, P. & Fossum, C. (2012). Global transcriptional response to ISCOM-Matrix adjuvant at the site of administration and in the draining lymph node early after intramuscular injection in pigs. Developmental and Comparative Immunology, 38(1), pp. 17-26.
IIIFossum, C., Hjertner, B., Ahlberg, V., Charerntantanakul, W., McIntosh, K., Fuxler, L., Balagunaseelan, N., Wallgren, P. & Lövgren Bengtsson, K. (2014). Early inflammatory response to the saponin adjuvant Matrix-M in the pig. Veterinary Immunology and Immunopathology, 158(1-2), pp. 53- 61.
IVAhlberg, V., Hjertner, B., Wallgren, P., Hellman, S., Lövgren Bengtsson, K. and Fossum, C. Transcriptional innate immune responses by Matrix-M adjuvant in pigs and its effects on natural infection. In manuscript.
Place of Publication:Uppsala
Publisher:Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8719-7
ISBN for electronic version:978-91-576-8720-3
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L70 Veterinary science and hygiene - General aspects
Subjects:(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Pathobiology
Agrovoc terms:swine, vaccines, vaccine adjuvants, saponins, natural immunity, immune response, interferons, cytokines, inflammation, experimental infection, in vitro culture, gene expression, pcr
Keywords:porcine, adjuvant, ISCOM-Matrix, Matrix-M, microarray, qPCR, interferon, infection model
URN:NBN:urn:nbn:se:slu:epsilon-e-3712
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-3712
ID Code:13698
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
External funders:FORMAS
Deposited By: Viktor Ahlberg
Deposited On:04 Oct 2016 07:22
Metadata Last Modified:04 Oct 2016 07:22

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