Influence of genetics and the pre-vaccination blood transcriptome on the variability of antibody levels after vaccination against Mycoplasma hyopneumoniae in pigs

Abstract

Background The impact of individual genetic and genomic variations on immune responses is an emerging lever investigated in vaccination strategies. In our study, we used genetic and pre-vaccination blood transcriptomic data to study vaccine effectiveness in pigs. Results A cohort of 182 Large White pigs was vaccinated against Mycoplasma hyopneumoniae (M. hyo) at weaning (28 days of age), with a booster 21 days later. Vaccine response was assessed by measuring seric M. hyo antibodies (Ab) at 0 (vaccination day), 21 (booster day), 28, 35, and 118 days post-vaccination (dpv). Inter-individual variability of M. hyo Ab levels was observed at all time points and the corresponding heritabilities ranged from 0.46 to 0.57. Ab persistence was higher in females than in males. Genome-wide association studies with a 658 K SNP panel revealed two genomic regions associated with variations of M. hyo Ab levels at 21 dpv at positions where immunity-related genes have been mapped, DAB2IP on chromosome 1, and ASAP1, CYRIB and GSDMC on chromosome 4. We studied covariations of Ab responses with the pre-vaccination blood transcriptome obtained by RNA-Seq for a subset of 82 pigs. Weighted gene correlation network and differential expression analyses between pigs that differed in Ab responses highlighted biological functions that were enriched in heme biosynthesis and platelet activation for low response at 21 dpv, innate antiviral immunity and dendritic cells for high response at 28 and 35 dpv, and cell adhesion and extracellular matrix for high response at 118 dpv. Sparse partial least squares discriminant analysis identified 101 genes that efficiently predicted divergent responders at all time points. We found weak negative correlations of M. hyo Ab levels with body weight traits, which revealed a trade-off that needs to be further explored. Conclusions We confirmed the influence of the host genetics on vaccine effectiveness to M. hyo and provided evidence that the pre-vaccination blood transcriptome co-varies with the Ab response. Our results highlight that both genetic markers and blood biomarkers could be used as potential predictors of vaccine response levels and more studies are required to assess whether they can be exploited in breeding programs.

Pyroptosis, metabolism, and tumor immune microenvironment

“…125,155 Ultraviolet irradiation can induce the expression of GSDMC mediated by the calcium/calcineurin/nuclear factor of activated T-cells, the cytoplasmic 1 (NFATc1) pathway and the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/matrix metalloproteinase 1 pathway in human skin keratinocytes. 156,157 Genomewide association studies show that GSDMC is associated with chronic back pain, 158 Mycoplasma hyopneumoniae (M. hyo) Ab variations in pigs, 159 lumbar spinal stenosis, 122 multi-type methylation in subchondral bone cartilage and osteoarthritis-related cartilage, 160,161 sciatica derived from lumbar disc herniation, 162 and monocyte counts. 163 GSDMC functions as an oncogene, mediating varieties of progressive processes involving types of tumors.…”

Signaling differences in peripheral blood mononuclear cells of high and low vaccine responders prior to, and following, vaccination in piglets

“…Our study utilizes young (<9 weeks old) piglets that may not appropriately represent a ‘baseline’ immune state at the time of vaccination described in other studies that use mature adults as cohorts, especially given that postnatal immune responses, hormonal factors, leukocyte populations, and cytokine production can vary within young, developing humans and livestock [6] , [16] , [24] , [39] , [40] . In swine, pre-vaccination differences in transcriptional networks were observed within PBMCs prior to M. hyopneumoniae -vaccination collected from high and low antibody responders defined at 118-days post-vaccination [5] . Thus, our work aligns with these previous studies supporting the hypothesis that the activity of the immune system prior to vaccination may have profound implications on the resulting immune response.…”

“…Thus, several -omic approaches have been applied to define host responses to vaccination, but the major emphasis has been on transcriptional analysis. This includes defining gene expression events in response to vaccines against yellow fever virus [14] , influenza virus [20] , [36] , [37] , hepatitis B virus [10] , shingles virus [27] tetanus toxoid [1] , foot-and-mouth-disease virus [22] , and Mycoplasma hyopneumoniae ( M. hyopneumoniae ) [5] , [29] . Defining patterns of gene expression within peripheral blood leukocytes that correlate with various quantifiable vaccine outcomes (eg.…”

Fighting the SARS-CoV-2 pandemic requires a global approach to understanding the heterogeneity of vaccine responses

“…Importantly, trained immunity has been demonstrated to enhance immune responses in the context of vaccination, initially with Bacillus Calmette-Guérin (BCG) [66][67][68] and the diphtheria, tetanus and pertussis (DTP) vaccines 66 and more recently with the influenza vaccines 55 . Studies have been performed to identify pre-vaccination signatures that predict vaccine efficacy and outcome [69][70][71][72] . Other studies have linked microbiota, metabolism, epigenetics and trained immunity shedding insight into the links of these critical pathways [73][74][75][76] .…”