The major histocompatibility complex homozygous inbred Babraham pig as a resource for veterinary and translational medicine

Schwartz, John C.; Hemmink, Johanneke D.; Graham, Simon P.; Tchilian, Elma; Charleston, Bryan; Hammer, Sabine E.; Ho, Chak-Sum; Hammond, John A.

doi:10.1111/tan.13281

Cited by 32 publications

(38 citation statements)

References 22 publications

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“…Differential protection induced by a live attenuated ASFV has been observed between NIH cc and dd minipigs that are inbred for different swine leukocyte antigen ( SLA ) class I and class II molecules [ 26 ]. In addition, the eight antigens were originally selected for their immunogenicity in the inbred Large White Babraham line of pigs which are homozygous at the SLA locus [ 29 , 46 ]. Low resolution genotyping of the twenty-four pigs immunized with Antigen Pools A, B and C identified ten SLA class I and eleven SLA class II haplotypes ( Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

A Pool of Eight Virally Vectored African Swine Fever Antigens Protect Pigs against Fatal Disease

et al. 2020

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Classical approaches to African swine fever virus (ASFV) vaccine development have not been successful; inactivated virus does not provide protection and use of live attenuated viruses generated by passage in tissue culture had a poor safety profile. Current African swine fever (ASF) vaccine research focuses on the development of modified live viruses by targeted gene deletion or subunit vaccines. The latter approach would be differentiation of vaccinated from infected animals (DIVA)-compliant, but information on which viral proteins to include in a subunit vaccine is lacking. Our previous work used DNA-prime/vaccinia-virus boost to screen 40 ASFV genes for immunogenicity, however this immunization regime did not protect animals after challenge. Here we describe the induction of both antigen and ASFV-specific antibody and cellular immune responses by different viral-vectored pools of antigens selected based on their immunogenicity in pigs. Immunization with one of these pools, comprising eight viral-vectored ASFV genes, protected 100% of pigs from fatal disease after challenge with a normally lethal dose of virulent ASFV. This data provide the basis for the further development of a subunit vaccine against this devastating disease.

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Section: Resultsmentioning

confidence: 99%

A Pool of Eight Virally Vectored African Swine Fever Antigens Protect Pigs against Fatal Disease

et al. 2020

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“…As previous work identified a D1-like Ig domain fragment encoded within the KIR2DL1 gene (Hammond et al 2009 ), we investigated KIR2DL1 mRNA splicing using PCR and cDNA from six animals leveraged from a recent MHC genotyping study (Schwartz et al 2018 ). Oligonucleotide primers were designed using Primer3 (Rozen and Skaletsky 2000 ) and supplied by Integrated DNA Technologies, BVBA (Leuven, Belgium).…”

Section: Methodsmentioning

confidence: 99%

The unique evolution of the pig LRC, a single KIR but expansion of LILR and a novel Ig receptor family

Schwartz

Hammond

2018

Immunogenetics

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The leukocyte receptor complex (LRC) encodes numerous immunoglobulin (Ig)-like receptors involved in innate immunity. These include the killer-cell Ig-like receptors (KIR) and the leukocyte Ig-like receptors (LILR) which can be polymorphic and vary greatly in number between species. Using the recent long-read genome assembly, Sscrofa11.1, we have characterized the porcine LRC on chromosome 6. We identified a ~ 197-kb region containing numerous LILR genes that were missing in previous assemblies. Out of 17 such LILR genes and fragments, six encode functional proteins, of which three are inhibitory and three are activating, while the majority of pseudogenes had the potential to encode activating receptors. Elsewhere in the LRC, between FCAR and GP6, we identified a novel gene that encodes two Ig-like domains and a long inhibitory intracellular tail. Comparison with two other porcine assemblies revealed a second, nearly identical, non-functional gene encoding a short intracellular tail with ambiguous function. These novel genes were found in a diverse range of mammalian species, including a pseudogene in humans, and typically consist of a single long-tailed receptor and a variable number of short-tailed receptors. Using porcine transcriptome data, both the novel inhibitory gene and the LILR were highly expressed in peripheral blood, while the single KIR gene, KIR2DL1, was either very poorly expressed or not at all. These observations are a prerequisite for improved understanding of immune cell functions in the pig and other species.Electronic supplementary materialThe online version of this article (10.1007/s00251-018-1067-1) contains supplementary material, which is available to authorized users.

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“…Despite centuries of agricultural selective breeding, the pig has maintained a significant level of SLA genetic diversity, with 227 class I and 211 class II alleles identified for Sus scrofa in the Immuno‐Polymorphism Database (IPD) MHC database to date, making analysis of the fine specificity of immune responses extremely difficult (Maccari et al, 2017). The inbred Babraham line of pigs, on the other hand, is SLA homozygous for class I SLA‐ 1*14:02; SLA‐2*11:04 and SLA‐3*04:03 and class II DRB1-*05:01, DQA-*01:03 and DQB1-*08:01 (Schwartz et al, 2018). This homozygosity enabled the use of peptide-SLA tetramers to the dominant NP antigen to track the CD8 response in tissues in this study (Tungatt et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Several inbred miniature pig breeds have been developed, including NIH and Yucatan, with defined swine leukocyte antigens (SLA type, the swine major histocompatibility complex) (Sachs et al, 1976; Choi et al, 2016). However, the inbred Babraham is the only example of a full-size inbred strain of pig, closely related to commercial breeds, making them an appropriate model to study diseases important to commercial pig production (Signer et al, 1999; Schwartz et al, 2018). The sharing of IAV strains between pigs and humans makes it an obvious species in which to study immunity to influenza and to test vaccines or therapeutic strategies prior to human clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Magnitude and kinetics of T cell and antibody responses during H1N1pdm09 infection in outbred and inbred Babraham pigs

Edmans

McNee

Porter

et al. 2020

Preprint

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We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize αβ, γδ T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to day 4-5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from day 5-6 post infection reaching a peak at 9-14 days. γδ cells produced cytokines ex vivo at day 2 post infection, while virus specific IFNγ producing γδ T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4 and γδ cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyse immune responses to influenza.

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The major histocompatibility complex homozygous inbred Babraham pig as a resource for veterinary and translational medicine

Cited by 32 publications

References 22 publications

A Pool of Eight Virally Vectored African Swine Fever Antigens Protect Pigs against Fatal Disease

A Pool of Eight Virally Vectored African Swine Fever Antigens Protect Pigs against Fatal Disease

The unique evolution of the pig LRC, a single KIR but expansion of LILR and a novel Ig receptor family

Magnitude and kinetics of T cell and antibody responses during H1N1pdm09 infection in outbred and inbred Babraham pigs

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