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Immune responses in pigs vaccinated with adjuvanted and non-adjuvanted A(H1N1)pdm/09 influenza vaccines used in human immunization programmes.

ABSTRACT: Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4(-)CD8(+) (cytotoxic) and CD4(+)CD8(+) (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions.

SUBMITTER: Lefevre EA

PROVIDER: S-EPMC3302873 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Immune responses in pigs vaccinated with adjuvanted and non-adjuvanted A(H1N1)pdm/09 influenza vaccines used in human immunization programmes.

Lefevre Eric A EA Carr B Veronica BV Inman Charlotte F CF Prentice Helen H Brown Ian H IH Brookes Sharon M SM Garcon Fanny F Hill Michelle L ML Iqbal Munir M Elderfield Ruth A RA Barclay Wendy S WS Gubbins Simon S Bailey Mick M Charleston Bryan B

PloS one 20120309 3

Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with ...[more]

PMID: 22427834

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Project description:Two decades after the introduction of oil-based vaccines in the control of bacterial and viral diseases in farmed salmonids, the mechanisms of induced side effects manifested as intra-abdominal granulomas remain unresolved. Side effects have been associated with generation of auto-antibodies and autoimmunity but underlying profile of the inflammatory and immune response has not been characterized. This study was undertaken with the aim to elucidate the inflammatory and immune mechanisms of granuloma formation at gene expression level associated with high and low side effect (granuloma) indices. Groups of Atlantic salmon parr were injected intraperitoneally with oil-adjuvanted vaccines containing either high or low concentrations of Aeromonas salmonicida or Moritella viscose antigens in order to induce polarized (severe and mild) granulomatous reactions. The established granulomatous reactions were confirmed by gross and histological methods at 3 months post vaccination when responses were known to have matured. The corresponding gene expression patterns in the head kidneys were profiled using salmonid cDNA microarrays followed by validation by real-time quantitative PCR (qPCR). qPCR was also used to examine the expression of additional genes known to be important in the adaptive immune response. Granulomatous lesions were observed in all vaccinated fish. Presence of severe granulomas were associated with a profile of up-regulation of innate immunity-related genes such as complement factors C1q and C6, mannose binding protein, lysozyme C, C-type lectin receptor, CD209, Cathepsin D, CD63, LECT-2, CC chemokine and metallothionein. In addition, IL-17A (Th17) was significantly up-regulated (p=0.009) in the group with severe granulomas as were arginase and IgM. None of the genes directly reflective of Th1 T cell lineage (IFN-γ, CD4) or Th2 (GATA-3) differentiation were differentially expressed. Granulomatous reactions following vaccination with oil-based vaccines in Atlantic salmon has the profile of strong expression of genes related to innate immune responses. The expression of IL-17A suggests an involvement of Th17 T cell lineage and is in conformity with strong infiltration of neutrophils and macrophages into inflamed areas. Arginase upregulation shows that macrophages in these reactions are alternatively activated, indicating a Th2-bias. To what extent the IL-17A profile reflects an autoimmune vaccine-based reaction remains elusive but would be in conformity with previous observations of autoimmune reactions in salmon vaccinated with oil-based vaccines. RNA from 12 head kidney samples (12 fish) per group were pooled into groups of 4. The RNA was amplified prior to hybridization to arrays. Three biological and 2 technical replicates (dye-swapped) were utilized in different combinations to hybridize to 18 arrays using RNA from fish with the least injection-site inflammatory reactions (FO-1) as the reference group. The assignment of microarrays to treatment groups for hybridization was randomised by using a random number generator. To minimize technical variability, target synthesis was done in batches of 6 where all treatment groups were equally represented.

Dataset Information

Immune responses in pigs vaccinated with adjuvanted and non-adjuvanted A(H1N1)pdm/09 influenza vaccines used in human immunization programmes.

Publications

Immune responses in pigs vaccinated with adjuvanted and non-adjuvanted A(H1N1)pdm/09 influenza vaccines used in human immunization programmes.

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