Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:26933193", "kind": "science-record", "revision": 7, "content_hash": "sha256:176602dc996d61269aa097f77a59379203e97e1a2c8e875470bbaff58acbae63", "created_at": "2026-11-01T15:40:16Z", "updated_at": "2026-11-01T21:58:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.", "doi": "10.1074/mcp.M115.055541", "pmid": "26933193", "authors": ["Djin-Ye Oh", "David J Dowling", "Saima Ahmed", "Hyungwon Choi", "Spencer Brightman", "Ilana Bergelson", "Sebastian T Berger", "John F Sauld", "Matthew Pettengill", "Alvin T Kho", "Henry J Pollack", "Hanno Steen", "Ofer Levy"], "journal": "Molecular & cellular proteomics : MCP", "year": 2016, "abstract": "Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles, paralleling responses to adjuvant-containing vaccines in vivo Age-specific in vitro modeling coupled with proteomics may provide fresh insight into the ontogeny of adjuvant action thereby informing targeted adjuvanted vaccine development for distinct age groups.", "claims": [{"id": "claim-method", "statement": "Proteins enriched after adjuvant treatment but not medium treatment were identified employing a customized version of the model-based statistical analysis tool QSpec based on SpC, using the count data model with paired design option and normalization by the total number of SpC in each sample replicate (45).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26933193", "locator": "sections[17] \"Label-free Protein Quantification and Analysis of Differential Protein Expression\" paragraph 2", "quote": "Proteins enriched after adjuvant treatment but not medium treatment were identified employing a customized version of the model-based statistical analysis tool QSpec based on SpC, using the count data model with paired design option and normalization by the total number of SpC in each sample replicate (45)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (40) via the PRIDE partner repository with the data set identifier PXD003534 and 10.6019/PXD003534.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:26933193", "locator": "sections[14] \"LC-MS Analysis\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (40) via the PRIDE partner repository with the data set identifier PXD003534 and 10.6019/PXD003534."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26933193"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD003534"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD003534"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:26933193", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1074/mcp.M115.055541", "sha256": "sha256:9ae10aa2cd0abee208e4ce2fae961a07a902dfdca65d206b4d564eeb48b6c6dc", "bytes": 78153, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1074/mcp.M115.055541", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5083103", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD003534", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD003534", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD003534", "version": null, "note": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (40) via the PRIDE partner repository with the data set identifier PXD003534 and 10.6019/PXD003534.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (40) via the PRIDE partner repository with the data set identifier PXD003534 and 10.6019/PXD003534.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Adjuvant Secretomes -  Adjuvant-induced human monocyte secretome profiles reveal adjuvant- and age-specific protein signatures", "resolution_checked_at": "2026-11-01T15:39:58Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:26933193:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:80832467a7f8b5131e5e76290de3bebd6f816cc0f101cbac1dd29b3fca5b896d", "bytes": 551, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[1]#TI", "version": null, "note": "Characteristics of adjuvants used in this study", "structure": {"pmcid": "PMC5083103", "section_index": 11, "section_title": "TLR Agonists, Adjuvants, Licensed Vaccines, and Assay Reagents", "row_count": 4, "column_count": 3}, "table": {"label": "Table I", "caption": "Characteristics of adjuvants used in this study", "rows": [["Name", "Mechanism of immune activation", "Current use"], ["AlPO", "NLRP3 Inflammasome, IRF3", "Component of licensed vaccines, including HBV, PCV"], ["MPLA", "TLR4 activation", "Approved for HPV vaccine (Cervarix)"], ["R848", "TLR7/8 activation, NLR activation", "R848 and additional TLR7/8 activating molecules are in preclinical development as vaccine adjuvants"]], "row_count": 4, "column_count": 3, "numeric_cells": 3, "header_rows": 1, "locator": "section[11]/table-wrap[1]#TI"}}, {"id": "asset:table:pmid:26933193:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cf9c06d77c738bb248eb0e50b858dfec42abeb1714e4d75f476d18e30b38be02", "bytes": 727, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[11]/table-wrap[2]#TII", "version": null, "note": "Characteristics of the licensed vaccines used in whole blood assays", "structure": {"pmcid": "PMC5083103", "section_index": 11, "section_title": "TLR Agonists, Adjuvants, Licensed Vaccines, and Assay Reagents", "row_count": 6, "column_count": 5}, "table": {"label": "Table II", "caption": "Characteristics of the licensed vaccines used in whole blood assays", "rows": [["Vaccine", "Trade name", "Abbreviation", "Manufacturer", "Adjuvant"], ["Hepatitis B", "Recombivax HB", "HepB", "Merck", "AAHS"], ["Human Papillomavirus", "Cervarix", "2vHPV", "GlaxoSmithKline", "Al(OH)3, MPLA"], ["H. influenzae type b, Meningococcal", "PedvaxHIB", "Hib-MenB", "Merck", "AAHS, OMPC"], ["Meningococcal", "Bexsero", "MenB", "GlaxoSmithKline", "Al(OH)3, OMVs"], ["Hepatitis B, Diphtheria, Tetanus, Pertussis, H. influenzae type b,", "Easyfive", "DTwP-Hep B-Hib", "Panacea Biotec", "AlPO, Inactivated whole cell B. pertussis"]], "row_count": 6, "column_count": 5, "numeric_cells": 3, "header_rows": 1, "locator": "section[11]/table-wrap[2]#TII"}}, {"id": "asset:table:pmid:26933193:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:1237ced728cc06f8f4e653230c820369dd1a987ae05623b3db65b5670ef09f90", "bytes": 9345, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[28]/table-wrap[1]#TIII", "version": null, "note": "Monocyte secretomes demonstrate activation of distinct canonical pathways varying by adjuvant and age. Ingenuity Pathway Analysis (IPA) was used to identify canonical pathways represented in the sets of adjuvant-induced proteins (n = 7 newborns and n = 6 adults). Proteins significantly up-regulated in the Alum-, MPLA-, and R848-induced secretomes. Shown are only those pathways represented by more than one protein in at least one of the adult/newborn datasets, with a p value < 0.05 per IPA; disease-specific pathways are excluded from the graph", "structure": {"pmcid": "PMC5083103", "section_index": 28, "section_title": "Pathway Analysis", "row_count": 165, "column_count": 4}, "table": {"label": "Table III", "caption": "Monocyte secretomes demonstrate activation of distinct canonical pathways varying by adjuvant and age. Ingenuity Pathway Analysis (IPA) was used to identify canonical pathways represented in the sets of adjuvant-induced proteins (n = 7 newborns and n = 6 adults). Proteins significantly up-regulated in the Alum-, MPLA-, and R848-induced secretomes. Shown are only those pathways represented by more than one protein in at least one of the adult/newborn datasets, with a p value < 0.05 per IPA; disease-specific pathways are excluded from the graph", "rows": [["Treatment", "Pathways", "-log10 (p value)", "Significantly up in newborn/adult"], ["Adult alum", "Caveolar-mediated endocytosis signaling", "2.56", "Yes"], ["", "Integrin signaling", "1.72", "Yes"], ["", "Actin cytoskeleton signaling", "1.66", "No"], ["", "MSP-RON signaling pathway", "1.31", "Yes"], ["Adult MPLA", "Acute phase response signaling", "1.24", "Yes"], ["", "LXR/RXR Activation", "8.56", "Yes"], ["", "Coagulation system", "6.39", "No"], ["", "Granulocyte adhesion and diapedesis", "6.22", "Yes"], ["", "Caveolar-mediated endocytosis signaling", "6.15", "Yes"], ["", "Leukocyte extravasation signaling", "5.70", "Yes"], ["", "Complement system", "4.96", "Yes"], ["", "FXR/RXR Activation", "4.75", "Yes"], ["", "Communication between innate and adaptive immune cells", "4.53", "Yes"], ["", "Extrinsic prothrombin activation pathway", "4.36", "No"], ["", "Dendritic cell maturation", "4.02", "No"], ["", "Agranulocyte adhesion and diapedesis", "3.93", "Yes"], ["", "IL-8 Signaling", "3.83", "Yes"], ["", "Intrinsic prothrombin activation pathway", "3.61", "No"], ["", "Antigen presentation pathway", "3.25", "No"], ["", "Inhibition of matrix metalloproteases", "3.22", "No"], ["", "Virus entry via endocytic pathways", "3.21", "Yes"], ["", "Glucocorticoid receptor signaling", "3.03", "No"], ["", "Paxillin signaling", "3.03", "Yes"], ["", "Dermatan sulfate degradation (Metazoa)", "2.78", "No"], ["", "Agrin interactions at neuromuscular junction", "2.50", "Yes"], ["", "IL-10 Signaling", "2.48", "Yes"], ["", "TREM1 signaling", "2.45", "Yes"], ["", "TR/RXR activation", "2.21", "No"], ["", "Crosstalk between dendritic cells and natural killer cells", "2.16", "Yes"], ["", "Cytotoxic T lymphocyte-mediated apoptosis of target cells", "2.09", "No"], ["", "Inhibition of angiogenesis by TSP1", "2.07", "Yes"], ["", "IL-6 signaling", "1.84", "Yes"], ["", "Role of PRRs in recognition of bacteria and viruses", "1.82", "Yes"], ["", "Hematopoiesis from pluripotent stem cells", "1.80", "No"], ["", "Relaxin signaling", "1.70", "Yes"], ["", "Role of cytokines in mediating Communication between immune cells", "1.66", "Yes"], ["", "melatonin signaling", "1.45", "No"], ["", "Macropinocytosis signaling", "1.45", "Yes"], ["", "Endothelin-1 signaling", "1.43", "No"], ["", "Ephrin receptor signaling", "1.40", "No"], ["", "NF-κB activation by viruses", "1.39", "Yes"], ["", "Toll-like receptor signaling", "1.39", "Yes"], ["", "Production of nitric oxide and reactive oxygen species in macrophages", "1.36", "No"], ["", "Integrin-linked kinase signaling", "1.35", "Yes"], ["Adult R848", "Acute phase response signaling", "12.8", "Yes"], ["", "LXR/RXR activation", "10.2", "Yes"], ["", "Granulocyte adhesion and diapedesis", "8.84", "Yes"], ["", "Agranulocyte adhesion and diapedesis", "6.21", "Yes"], ["", "FXR/RXR activation", "6.08", "Yes"], ["", "Leukocyte extravasation signaling", "5.89", "Yes"], ["", "Complement system", "5.05", "No"], ["", "IL-8 signaling", "4.98", "Yes"], ["", "Coagulation system", "4.89", "No"], ["", "Inhibition of matrix metalloproteases", "4.75", "Yes"], ["", "Communication between innate and adaptive immune cells", "4.65", "Yes"], ["", "Extrinsic prothrombin activation pathway", "4.44", "No"], ["", "Glucocorticoid receptor signaling", "4.02", "Yes"], ["", "IL-6 signaling", "3.93", "Yes"], ["", "IL-10 signaling", "3.74", "Yes"], ["", "TREM1 signaling", "3.70", "Yes"], ["", "Intrinsic prothrombin activation pathway", "3.68", "No"], ["", "Dendritic cell maturation", "3.17", "No"], ["", "Paxillin signaling", "3.12", "Yes"], ["", "Chondroitin sulfate degradation (Metazoa)", "2.89", "No"], ["", "Role of cytokines in mediating communication between immune cells", "2.89", "Yes"], ["", "Dermatan sulfate degradation (Metazoa)", "2.83", "No"], ["", "Role of PRRs in recognition of bacteria and viruses", "2.82", "Yes"], ["", "Cytokine production in macrophages and Th cells by IL-17A/IL-17F", "2.61", "No"], ["", "Agrin interactions at neuromuscular junction", "2.57", "Yes"], ["", "Toll-like receptor signaling", "2.46", "Yes"], ["", "NF-κB signaling", "2.28", "Yes"], ["", "Crosstalk between dendritic cells and natural killer cells", "2.22", "Yes"], ["", "Clathrin-mediated endocytosis signaling", "2.15", "No"], ["", "Inhibition of angiogenesis by TSP1", "2.11", "Yes"], ["", "HIF1α signaling", "2.07", "Yes"], ["", "Oncostatin M signaling", "2.06", "Yes"], ["", "Integrin signaling", "2.06", "Yes"], ["", "IL-17A signaling in fibroblasts", "2.04", "Yes"], ["", "Hematopoiesis from pluripotent stem cells", "1.84", "No"], ["", "MSP-RON signaling pathway", "1.81", "Yes"], ["", "Macropinocytosis signaling", "1.49", "Yes"], ["", "NF-κB activation by viruses", "1.43", "Yes"], ["", "Integrin-linked kinase signaling", "1.41", "Yes"], 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via endocytic pathways", "2.42", "No"], ["", "Role of PRRs in recognition of bacteria and viruses", "2.18", "No"], ["", "Acute phase response signaling", "1.89", "No"], ["", "Dendritic cell maturation", "1.89", "No"], ["", "Agranulocyte adhesion and diapedesis", "1.86", "No"], ["", "Integrin-linked kinase signaling", "1.83", "No"], ["Newborn MPLA", "Granulocyte adhesion and diapedesis", "8.22", "Yes"], ["", "IL-8 signaling", "6.52", "Yes"], ["", "Leukocyte extravasation signaling", "6.37", "Yes"], ["", "LXR/RXR activation", "6.30", "Yes"], ["", "Agranulocyte adhesion and diapedesis", "5.37", "Yes"], ["", "Caveolar-mediated endocytosis signaling", "4.53", "Yes"], ["", "Acute phase response signaling", "4.25", "Yes"], ["", "Paxillin signaling", "3.99", "Yes"], ["", "IL-10 signaling", "3.20", "Yes"], ["", "TREM1 signaling", "3.16", "Yes"], ["", "Integrin signaling", "2.87", "Yes"], ["", "Inhibition of angiogenesis by TSP1", "2.55", "Yes"], ["", "Complement system", "2.55", "Yes"], ["", "IL-6 signaling", "2.53", "Yes"], ["", "Role of PRRs in recognition of bacteria and viruses", "2.50", "No"], ["", "FXR/RXR activation", "2.44", "Yes"], ["", "Role of cytokines in mediating Communication between immune cells", "2.14", "Yes"], ["", "Agrin interactions at neuromuscular junction", "1.92", "Yes"], ["", "Macropinocytosis signaling", "1.91", "Yes"], ["", "NF-κB activation by viruses", "1.85", "Yes"], ["", "Toll-like receptor signaling", "1.85", "Yes"], ["", "Communication between innate and adaptive immune cells", "1.76", "Yes"], ["", "Signaling by Rho family GTPases", "1.70", "No"], ["", "Virus entry via endocytic pathways", "1.69", "Yes"], ["", "Crosstalk between dendritic cells and natural killer cells", "1.69", "Yes"], ["", "Cytokine production in macrophages and Th cells by IL-17A/IL-17F", "1.36", "No"], ["Newborn R848", "Granulocyte adhesion and diapedesis", "7.74", "Yes"], ["", "IL-8 signaling", "6.12", "Yes"], ["", "Leukocyte extravasation signaling", "5.97", "Yes"], ["", "LXR/RXR activation", "5.96", "Yes"], ["", "Inhibition of matrix metalloproteases", "5.42", "Yes"], ["", "Agranulocyte adhesion and diapedesis", "5.03", "Yes"], ["", "Acute phase response signaling", "3.97", "Yes"], ["", "Paxillin signaling", "3.76", "Yes"], ["", "Glucocorticoid receptor signaling", "3.11", "Yes"], ["", "IL-10 signaling", "3.03", "Yes"], ["", "Macropinocytosis signaling", "3.03", "Yes"], ["", "TREM1 signaling", "3.00", "Yes"], ["", "Integrin signaling", "2.66", "Yes"], ["", "HIF1α signaling", "2.54", "Yes"], ["", "Inhibition of angiogenesis by TSP1", "2.44", "Yes"], ["", "Oncostatin M signaling", "2.38", "Yes"], ["", "IL-6 signaling", "2.37", "Yes"], ["", "IL-17A signaling in fibroblasts", "2.36", "Yes"], ["", "Role of PRRs in recognition of bacteria and viruses", "2.34", "Yes"], ["", "FXR/RXR activation", "2.28", "Yes"], ["", "MSP-RON signaling pathway", "2.13", "Yes"], ["", "Role of cytokines in mediating communication between immune cells", "2.03", "Yes"], ["", 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