Molecular signatures of clinically tested vaccine adjuvants
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE85339 | GEO | 2017/01/09
SECONDARY ACCESSION(S): PRJNA338195
REPOSITORIES: GEO
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Project description:A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.
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Project description:Authorization of the Matrix-M-adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization (WHO) for malaria prevention in children is a milestone in the fight against malaria. Yet, to meet the unprecedented demand for malarial vaccines, there is a pressing need for additional adjuvants that induce robust and durable vaccine-induced immunity. Here, we performed a comparative assessment of three clinically relevant adjuvants (an alum formulation of the TLR7/8 agonist 3M-052 (3M-052+Alum), the TLR4 agonist GLA-LSQ (GLA in liposome QS-21 formulation), and Matrix-M, the currently approved adjuvant for R21) for their capacity to induce durable immune responses to the R21 malaria vaccine in non-human primates. Immunization of macaques with R21 adjuvanted with 3M-052+Alum on a 0, 8, and 24-week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/Matrix-M vaccine and persisted up to 72 weeks with a half-life of 337 (264 – 459) days. A booster dose at 72 weeks induced an antigen-specific recall response, similar to the R21/Matrix-M vaccination. In contrast, R21/GLA-LSQ immunization induced a considerably lower and short-lived response. Consistent with the durability of serum antibody responses, Matrix-M and 3M-052+Alum induced long-lived plasma cells in the bone marrow and other tissues, including the spleen, but GLA-LSQ stimulated only short-lived plasmablasts. Finally, we show distinct innate immune signatures early after vaccination with these adjuvants. While 3M-052+Alum stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, Matrix-M induced an enhanced expression of interferon- and Th2-related signatures more highly after the booster vaccination. Collectively, these findings provide a comparative database on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M-052+Alum as an additional adjuvant for the R21 malaria vaccine.
2024-06-01 | GSE249806 | GEO
Project description:Nanoparticles and microparticles are widely used as vaccine adjuvants to enhance the immune response and improve the stability of antigens. While aluminum salt is one of the most common adjuvants approved for human use, its immunostimulatory capacity is suboptimal. In this study, we modified risedronate, an immunostimulant and anti‐osteoporotic drug, to create the zinc salt particle-based risedronate (Zn-RS), also termed particulate risedronate. Compared to soluble risedronate, the Zn-RS adjuvant demonstrated increased recruitment of innate cells, enhanced antigen uptake locally, and a similar antigen depot effect as aluminum salt. Furthermore, the Zn-RS adjuvant directly and quickly stimulated immune cells, accelerated the formulation of germinal centers in the lymph nodes, and facilitated the rapid production of antibodies. Importantly, the Zn-RS adjuvant exhibited superior performance in both young and aged mice, effectively protecting against respiratory diseases such as SARS-CoV-2 infection. Consequently, particulate risedronate showed great potential as a universal vaccine adjuvant, particularly beneficial for vaccines targeting the susceptible elderly.
2024-08-01 | GSE239646 | GEO
Project description:Nanoparticles and microparticles are widely used as vaccine adjuvants to enhance the immune response and improve the stability of antigens. While aluminum salt is one of the most common adjuvants approved for human use, its immunostimulatory capacity is suboptimal. In this study, we modified risedronate, an immunostimulant and anti‐osteoporotic drug, to create the zinc salt particle-based risedronate (Zn-RS), also termed particulate risedronate. Compared to soluble risedronate, the Zn-RS adjuvant demonstrated increased recruitment of innate cells, enhanced antigen uptake locally, and a similar antigen depot effect as aluminum salt. Furthermore, the Zn-RS adjuvant directly and quickly stimulated immune cells, accelerated the formulation of germinal centers in the lymph nodes, and facilitated the rapid production of antibodies. Importantly, the Zn-RS adjuvant exhibited superior performance in both young and aged mice, effectively protecting against respiratory diseases such as SARS-CoV-2 infection. Consequently, particulate risedronate showed great potential as a universal vaccine adjuvant, particularly beneficial for vaccines targeting the susceptible elderly.
2024-08-01 | GSE239643 | GEO
Project description:This proteomics data are generated from mouse skin treated with physical radiofrequency adjuvant and common chemical adjuvants, such as AddaVax, MPL, Alum, MPL/Alum.
2022-11-09 | MSV000090681 | MassIVE
Project description:Protection from pathogens relies on both humoral (antibody-mediated) and cellular (T cell-mediated) responses. While infections robustly elicit both of these types of immunity, currently approved vaccine adjuvants largely fail to induce significant T cell responses. However, recent work by our lab and others suggests that the mechanisms governing vaccine-elicited T cells (Tvac) may be substantially different than those governing infection-elicited T cells (Tinf). We have recently demonstrated that optimal subunit vaccine-elicited T cell responses rely on different cytokine signals (IL-27 and 15) and metabolic function (oxidative phosphorylation vs. aerobic glycolysis) leading to phenotypically and functionally different outcomes (memory vs. effector). Our goal was to investigate the transcriptional programming that promotes Tvac formation. Using a bulk RNAsequencing approach we compared WT Tvac at day 3 post immunization to Tvac where IL-27 or IL-15 signaling was absent, to Tinf at day 4 post infectious challenge, or to naive OT-1 T cells.
2023-07-14 | GSE237415 | GEO
Project description:Purpers: To verify the effect of adjuvants (Alhydrogel, AS02, AS03) on immunity of BALB/c mice induced by RSV-F subunit vaccine at the level of gene expression. Methodes:Four groups ((1) RSV-F, (2) RSV-F + Alhydrogel, (3) RSV-F + AS02, and (4) RSV-F + AS03) were analyzed in the transcriptome sequencing experiment. On days 0 and 14, vaccines were administered intramuscularly into the thigh muscle. 14 days after the last vaccination, blood samples from three BALB/c mice in each group were collected. RNA degradation and contamination were assayed. Concentration were measured using a Qubit RNA Assay Kit and a Qubit 2.0 Fluorometer. RNA integrity was assessed using an RNA Nano 6000 Assay Kit and a Bioanalyzer 2100 system. 3 μg RNA per qualified sample was used as input material for RNA library preparation. Sequencing libraries were generated using a NEBNext Ultra RNA Library Prep Kit for Illumina (New England Biolabs, US), and unique index codes were added to each sample. Result: We obtained sample gene expression information. The subsequent differentially expressed gene GO and KEGG enrichment analysis result suggested that AS02 regulates immune balance by activating TLR-4 and promotes Th1-type immune responses.
2020-01-15 | GSE143617 | GEO
Project description:Respiratory syncytial virus (RSV) F subunit vaccine with adjuvants affect immunity in BALB/c mice
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Project description:Adjuvants are critical for the success of vaccines, and agonists for microbial pattern recognition receptors are promising new candidates. A mechanism for the immune enhancing role of adjuvants is to stimulate innate immunity. We studied the innate immune response in humans to synthetic double stranded RNA (poly ICLC), a ligand for TLR3 and MDA-5 cytosolic RNA helicase. Transcriptional analysis of blood samples from eight volunteers, after subcutaneous administration of poly ICLC showed upregulation of genes involved in multiple innate immune pathways in all subjects, including interferon and inflammasome signaling. Blocking of type I interferon receptor ex vivo significantly dampened the response to poly IC. Comparative transcriptional analysis showed that several innate pathways were similarly induced in volunteers immunized with the highly efficacious Yellow Fever Vaccine. Therefore a chemically defined microbial agonist like poly ICLC can be a reliable and authentic microbial mimic for inducing innate immunity, here for a live attenuated viral vaccine in humans. GSM813292-GSM813386: RNA expression obtained at different time points from Human blood after poly ICLC administration compared to RNA expression obtained from Human blood after placebo administration GSM813387-GSM813410: Blocking of type I interferon receptor ex vivo followed by poly IC stimulation
2011-10-11 | E-GEOD-32862 | biostudies-arrayexpress
Project description:Protection from pathogens relies on both humoral (antibody-mediated) and cellular (T cell-mediated) responses. While infections robustly elicit both of these types of immunity, currently approved vaccine adjuvants largely fail to induce significant T cell responses. However, recent work by our lab and others suggests that the mechanisms governing vaccine-elicited T cells (Tvac) may be substantially different than those governing infection-elicited T cells (Tinf). We have recently demonstrated that optimal subunit vaccine-elicited T cell responses rely on different cytokine signals (IL-27 and 15) and metabolic function (oxidative phosphorylation vs. aerobic glycolysis) leading to phenotypically and functionally different outcomes (memory vs. effector). Our goal was to investigate the transcriptional programming that promotes Tvac formation. Using a single-cell RNA-seq approach, we compared Tvac and Tinf at day 7 post-immunization or infectious challenge to determine the heterogenity of CD8 T cell responses at this peak timepoint.
2023-07-14 | GSE237416 | GEO