Systems Immunology Characterization of Novel Vaccine Formulations for Mycoplasma hyopneumoniae Bacterins

Abstract

We characterized five different vaccine candidates and a commercial vaccine in terms of safety, immunogenicity and using a systems vaccinology approach, with the aim to select novel vaccine candidates against Mycoplasma hyopneumoniae . Seven groups of six M. hyopneumoniae -free piglets were primo- and booster vaccinated with the different experimental bacterin formulations, the commercial vaccine Hyogen® as a positive control or PBS as a negative control. The experimental bacterin was formulated with cationic liposomes + c-di-AMP (Lipo_AMP), cationic liposomes + Toll-like receptor (TLR) 2/1, TLR7, and TLR9 ligands (TLR ligands; Lipo_TLR), micro-particles + TLR ligands (PLGA_TLR), squalene-in-water emulsion + TLR ligands (SWE_TLR), or DDA:TDB liposomes (Lipo_DDA:TDB). Lipo_DDA:TDB and Lipo_AMP were the most potent in terms of serum antibody induction, and Lipo_DDA:TDB, Lipo_AMP, and SWE_TLR significantly induced Th1 cytokine-secreting T-cells. Only PLGA_TLR appeared to induce Th17 cells, but was unable to induce serum antibodies. The transcriptomic analyses demonstrated that the induction of inflammatory and myeloid cell blood transcriptional modules (BTM) in the first 24 h after vaccination correlated well with serum antibodies, while negative correlations with the same modules were found 7 days post-vaccination. Furthermore, many cell cycle and T-cell BTM upregulated at day seven correlated positively with adaptive immune responses. When comparing the delivery of the identical TLR ligands with the three formulations, we found SWE_TLR to be more potent in the induction of an early innate immune response, while the liposomal formulation more strongly promoted late cell cycle and T-cell BTM. For the PLGA formulation we found signs of a delayed and weak perturbation of these BTM. Lipo_AMP was found to be the most potent vaccine at inducing a BTM profile similar to that correlating with adaptive immune response in this and other studies. Taken together, we identified four promising vaccine candidates able to induce M. hyopneumoniae -specific antibody and T-cell responses. In addition, we have adapted a systems vaccinology approach developed for human to pigs and demonstrated its capacity in identifying early immune signatures in the blood relating to adaptive immune responses. This approach represents an important step in a more rational design of efficacious vaccines for pigs.

High-Resolution Profiling of Innate Immune Responses by Porcine Dendritic Cell Subsets in vitro and in vivo

“…The molecular signatures of in vivo activated DC were also analyzed by “ranked gene set enrichment analysis” (GSEA) ( 24 ) using a selection of blood transcription modules (BTM) defined by Li et al ( 25 ) and modified for pigs as previously described ( 26 ). For this selection, all cell-type specific and non-classified BTM [“TBA” in Li et al ( 25 )] were omitted resulting in 86 BTM (M4.0, M4.1, M4.2, M4.3, M4.4, M4.5, M4.6, M4.7, M4.8, M4.10, M4.12, M5.0, M6, M13, M14, M15, M16, M22.0, M22.1, M23, M24, M25, M27.0, M27.1, M28, M29, M33, M34, M37.3, M38, M39, M40, M43.0, M43.1, M50, M51, M53, M59, M64, M65, M67, M68, M71, M75, M76, M77, M78, M86.0, M86.1, M92, M95.0, M95.1, M103, M109, M111.0, M111.1, M112.0, M112.1, M114.1, M115, M119, M122, M127, M129, M138, M139, M143, M144, M146, M147, M150, M158.0, M158.1, M165, M168, M169, M200, M209, M216, M219, M225, M226, M230, M250, S10, S11), which mainly inform on antigen presentation, inflammation, interferon (IFN) type I responses, metabolic processes and cell cycle.…”

Contagious Bovine and Caprine Pleuropneumonia: a research community’s recommendations for the development of better vaccines

“…Furthermore, many cell surface markers are not unique to one population. Therefore, alternative approaches may be useful, such as those arising from the field of systems immunology 75 and systems vaccinology 76 , which have recently been adapted from humans to livestock species 77,78 . High-throughput technologies such as RNA sequencing coupled with data analysis allow the interrogation of hosts' intracellular and intercellular interactions to understand the entire immune system better.…”

Biological Importance of Microbes in Agriculture, Food and Pharmaceutical Industry: A Review

“…Vaccine production A vaccine totally comprises biological productions from an agent that is disease causing microorganisms or resembles with disease causing microorganisms and have ability to provide immunity against that particular disease, from the causal organism, of which the biological preparation was actually made [34]. These biological preparations are mostly obtained from the killed or weekend form of microbes or may be made from surface protein or toxins of disease causing organism.…”