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J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Keyhole limpet hemocyanin (KLH) is a large copper-containing glycoprotein derived from the marine gastropod Megathura crenulata. Originally functioning as an oxygen transport molecule, KLH has gained considerable attention in biomedical research due to its exceptional immunogenic and immunostimulatory properties. Its complex quaternary structure, extensive glycosylation, and xenogeneic origin contribute to its ability to induce robust humoral and cellular immune responses in mammals without significant toxicity. These characteristics have established KLH as one of the most widely used carrier proteins in vaccine development and as a valuable model antigen for the investigation of adaptive immune responses. This review summarizes current knowledge on the biological origin, molecular structure, biosynthesis, and post-translational processing of KLH, with particular emphasis on its unique glycan architecture and its contribution to immunogenicity. Advances in glycomic and structural analyses have revealed an extraordinary diversity of N-linked glycans that distinguish KLH from mammalian glycoproteins and play a central role in immune recognition. The review further discusses methods for KLH isolation, purification, and characterization, as well as its application in experimental and clinical immunology as a standardized tool for assessing antigen-specific immune responses. In addition, the therapeutic and translational potential of KLH is examined across multiple biomedical fields. Particular attention is given to its use as a carrier protein in conjugate vaccines, its role in cancer immunotherapy, and its emerging applications in the development of vaccines and immunotherapeutic strategies targeting neurodegenerative diseases, atherosclerosis, and substance use disorders. Collectively, the available evidence highlights KLH as a unique marine-derived biomolecule that bridges glycobiology, immunology, and translational medicine, and continues to serve as an important platform for the development of next-generation immunotherapeutics and vaccine technologies.<\/jats:p>","DOI":"10.3390\/ijms27177921","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"7921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unlocking the Potency of Keyhole Limpet Hemocyanin: Structural Insights, Immunological Mechanisms, and Therapeutic Frontiers"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-0642-3387","authenticated-orcid":false,"given":"Paula","family":"Cermakova","sequence":"first","affiliation":[{"name":"Department of Galenic Pharmacy, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1996-6812","authenticated-orcid":false,"given":"Ondrej","family":"Cehlar","sequence":"additional","affiliation":[{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4736-4592","authenticated-orcid":false,"given":"Juraj","family":"Piestansky","sequence":"additional","affiliation":[{"name":"Department of Galenic Pharmacy, Faculty of Pharmacy, Comenius University, Odbojarov 10, 832 32 Bratislava, Slovakia"},{"name":"Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska cesta 9, 845 10 Bratislava, Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Bonett-Calzada, B., Valenzuela-Qui\u00f1onez, F., Del R\u00edo-Portilla, M.A., Bayona-V\u00e1squez, N.J., Vargas-Peralta, C.E., Hyde, J.R., and Lafarga-De la Cruz, F. (2024). Genetic Insights into the Giant Keyhole Limpet (Megathura crenulata), an Eastern Pacific Coastal Endemic: Complete Mitogenome, Phylogenetics, Phylogeography, and Historical Demography. Genes, 15.","DOI":"10.3390\/genes15101303"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/raq.12190","article-title":"Aquaculture of Two Commercially Important Molluscs (Abalone and Limpet): Existing Knowledge and Future Prospects","volume":"10","author":"Mau","year":"2018","journal-title":"Rev. Aquac."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1086\/700181","article-title":"Discovery of Novel Hemocyanin-like Genes in Metazoans","volume":"235","author":"Schrago","year":"2018","journal-title":"Biol. Bull."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.dci.2018.04.017","article-title":"Hemocyanin-Derived Phenoloxidase Reaction Products Display Anti-Infective Properties","volume":"86","author":"Coates","year":"2018","journal-title":"Dev. Comp. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"132041","DOI":"10.1016\/j.ijbiomac.2024.132041","article-title":"A Comprehensive Review on Hemocyanin from Marine Products: Structure, Functions, Its Implications for the Food Industry and Beyond","volume":"269","author":"Ji","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/0305-0491(95)02091-8","article-title":"Keyhole Limpet Hemocyanin: Structural and Functional Characterization of Two Different Subunits and Multimers","volume":"113","author":"Swerdlow","year":"1996","journal-title":"Comp. Biochem. Physiol. Part B Biochem. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0019-2791(64)90030-8","article-title":"Immunochemical Properties of Hemocyanin","volume":"1","author":"Weigle","year":"1964","journal-title":"Immunochemistry"},{"key":"ref_8","first-page":"61","article-title":"Antigen Dose in the Human Immune Response. Dose-Relationships in the Human Immune Response to Keyhole Limpet Hemocyanin","volume":"78","author":"Curtis","year":"1971","journal-title":"J. Lab. Clin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0968-4328(99)00036-0","article-title":"Keyhole Limpet Hemocyanin (KLH): A Biomedical Review","volume":"30","author":"Harris","year":"1999","journal-title":"Micron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1038\/s41467-023-38039-x","article-title":"Engineering Protein-Based Therapeutics through Structural and Chemical Design","volume":"14","author":"Ebrahimi","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Holz, E., Darwish, M., Tesar, D.B., and Shatz-Binder, W. (2023). A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020600"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/cts.13457","article-title":"In Vivo Human Keyhole Limpet Hemocyanin Challenge in Early Phase Drug Development: A Systematic Review","volume":"16","author":"Drennan","year":"2023","journal-title":"Clin. Transl. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Pousa, S., Ramos-Berm\u00fadez, P.E., Besada, V., Cabrales-Rico, A., Garay, H.E., Rodr\u00edguez-Mall\u00f3n, A., Zettl, K., Wi\u015bniewski, J.R., and Gonz\u00e1lez, L.J. (2024). Characterization by LC-MS\/MS of Two Conjugate Vaccines Using KLH as Carrier Protein. ChemRxiv.","DOI":"10.26434\/chemrxiv-2024-nslhn-v2"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41569-020-0407-7","article-title":"Developing a Vaccine against Atherosclerosis","volume":"17","author":"Hansson","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1124\/pr.117.013904","article-title":"Conjugate Vaccine Immunotherapy for Substance Use Disorder","volume":"69","author":"Bremer","year":"2017","journal-title":"Pharmacol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e000342","DOI":"10.1136\/jitc-2019-000342","article-title":"Globo H-KLH Vaccine Adagloxad Simolenin (OBI-822)\/OBI-821 in Patients with Metastatic Breast Cancer: Phase II Randomized, Placebo-Controlled Study","volume":"8","author":"Huang","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/S0022-5347(17)36172-4","article-title":"Immunotherapy of Murine Bladder Cancer with Keyhole Limpet Hemocyanin (KLH)","volume":"149","author":"Lamm","year":"1993","journal-title":"J. Urol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kawakami, R., Nozato, Y., Nakagami, H., Ikeda, Y., Shimamura, M., Yoshida, S., Sun, J., Kawano, T., Takami, Y., and Noma, T. (2018). Development of Vaccine for Dyslipidemia Targeted to a Proprotein Convertase Subtilisin\/Kexin Type 9 (PCSK9) Epitope in Mice. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191895"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.neures.2017.01.003","article-title":"Prophylactic Active Immunization with a Novel Epitope Vaccine Improves Cognitive Ability by Decreasing Amyloid Plaques and Neuroinflammation in APP\/PS1 Transgenic Mice","volume":"119","author":"Ding","year":"2017","journal-title":"Neurosci. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1684\/ecn.2015.0365","article-title":"Evaluation of Two Different Adjuvants with Immunogenic Uroplakin 3A-Derived Peptide for Their Ability to Evoke an Immune Response in Mice","volume":"26","author":"Izgi","year":"2015","journal-title":"Eur. Cytokine Netw."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s12551-017-0349-4","article-title":"Molluscan Hemocyanin: Structure, Evolution, and Physiology","volume":"10","author":"Kato","year":"2017","journal-title":"Biophys. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.jmb.2008.10.080","article-title":"Keyhole Limpet Hemocyanin: 9-\u00c5 CryoEM Structure and Molecular Model of the KLH1 Didecamer Reveal the Interfaces and Intricate Topology of the 160 Functional Units","volume":"385","author":"Gatsogiannis","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0968-4328(97)00011-5","article-title":"Keyhole Limpet Hemocyanin (KLH), II: Characteristic Reassociation Properties of Purified KLH1 and KLH2","volume":"28","author":"Harris","year":"1997","journal-title":"Micron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1002\/iub.435","article-title":"The Refined Structure of Functional Unit h of Keyhole Limpet Hemocyanin (KLH1-h) Reveals Disulfide Bridges","volume":"63","author":"Jaenicke","year":"2011","journal-title":"IUBMB Life"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1744-7410.2011.00249.x","article-title":"Synthesis of Keyhole Limpet Hemocyanin by the Rhogocytes of Megathura crenulata","volume":"130","author":"Martin","year":"2011","journal-title":"Invertebr. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s004410100368","article-title":"Rhogocytes (Pore Cells) as the Site of Hemocyanin Biosynthesis in the Marine Gastropod Haliotis tuberculata","volume":"304","author":"Albrecht","year":"2001","journal-title":"Cell Tissue Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/2041-9139-5-6","article-title":"A New Haemocyanin in Cuttlefish (Sepia officinalis) Eggs: Sequence Analysis and Relevance during Ontogeny","volume":"5","author":"Thonig","year":"2014","journal-title":"EvoDevo"},{"key":"ref_28","unstructured":"Oakes, F.R. (2005). Non-Lethal Method for Extracting Crude Hemocyanin from Gastropod Molluscs. (6852338B2), U.S. Patent."},{"key":"ref_29","unstructured":"Varki, A., Cummings, R.D., Esko, J.D., Stanley, P., Hart, G.W., Aebi, M., Mohnen, D., Kinoshita, T., Packer, N.H., and Prestegard, J.H. (2022). Essentials of Glycobiology, Cold Spring Harbor Laboratory Press. [4th ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Onigbinde, S., Adeniyi, M., Daramola, O., Chukwubueze, F., Bhuiyan, M.M.A.A., Nwaiwu, J., Bhattacharjee, T., and Mechref, Y. (2025). Glycomics in Human Diseases and Its Emerging Role in Biomarker Discovery. Biomedicines, 13.","DOI":"10.3390\/biomedicines13082034"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.cell.2006.08.019","article-title":"Glycosylation in Cellular Mechanisms of Health and Disease","volume":"126","author":"Ohtsubo","year":"2006","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000052389","article-title":"Keyhole Limpet Hemocyanin: Molecular Structure of a Potent Marine Immunoactivator","volume":"37","author":"Harris","year":"2000","journal-title":"Eur. Urol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.2165\/11530550-000000000-00000","article-title":"Glycosylation of Therapeutic Proteins","volume":"24","author":"Griebenow","year":"2010","journal-title":"BioDrugs"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Staudacher, E. (2021). Mollusc N-Glycosylation: Structures, Functions and Perspectives. Biomolecules, 11.","DOI":"10.3390\/biom11121820"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1046\/j.1432-1033.2002.03244.x","article-title":"Hemocyanin from the Keyhole Limpet Megathura crenulata (KLH) Carries a Novel Type of N-glycans with Gal(\u03b21\u20136)Man-motifs","volume":"269","author":"Kurokawa","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1084\/jem.165.3.865","article-title":"Schistosoma mansoni Shares a Protective Carbohydrate Epitope with Keyhole Limpet Hemocyanin","volume":"165","author":"Grzych","year":"1987","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Dolashka, P., Daskalova, A., Dolashki, A., and Voelter, W. (2020). De Novo Structural Determination of the Oligosaccharide Structure of Hemocyanins from Molluscs. Biomolecules, 10.","DOI":"10.3390\/biom10111470"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0167-4838(01)00152-2","article-title":"Isolation and Spectroscopic Characterization of the Structural Subunits of Keyhole Limpet Hemocyanin","volume":"1546","author":"Abrashev","year":"2001","journal-title":"Biochim. Biophys. Acta Protein Struct. Mol. Enzymol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0300-9629(89)90534-3","article-title":"Hemocyanin Levels in the Giant Keyhole Limpet, Megathura crenulata, from the Coast of California","volume":"94","author":"Senozan","year":"1989","journal-title":"Comp. Biochem. Physiol. Part A Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.cbpb.2004.03.009","article-title":"The Effect of Captivity and Diet on KLH Isoform Ratios in Megathura crenulata","volume":"138","author":"Oakes","year":"2004","journal-title":"Comp. Biochem. Physiol. Part A Mol. Integr. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1111\/bcp.12422","article-title":"Keyhole Limpet Haemocyanin\u2014A Model Antigen for Human Immunotoxicological Studies","volume":"78","author":"Swaminathan","year":"2014","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.yrtph.2014.02.008","article-title":"The T-Cell-Dependent Antibody Response Assay in Nonclinical Studies of Pharmaceuticals and Chemicals: Study Design, Data Analysis, Interpretation","volume":"69","author":"Lebrec","year":"2014","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1111\/bcp.14588","article-title":"A Randomized Controlled Trial with a Delayed-type Hypersensitivity Model Using Keyhole Limpet Haemocyanin to Evaluate Adaptive Immune Responses in Man","volume":"87","author":"Saghari","year":"2020","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"43486","DOI":"10.1038\/srep43486","article-title":"Monitoring of Dynamic Changes in Keyhole Limpet Hemocyanin (KLH)-Specific B Cells in KLH-Vaccinated Cancer Patients","volume":"7","author":"Wimmers","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1111\/bcp.12172","article-title":"A Novel Assay to Measure B Cell Responses to Keyhole Limpet Haemocyanin Vaccination in Healthy Volunteers and Subjects with Systemic Lupus Erythematosus","volume":"76","author":"Ferbas","year":"2013","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Saghari, M., Jansen, M.A.A., Grievnik, H.W., Rissmann, R., and Moerland, M. (2022). Characterization of KLH-Driven Immune Responses in Clinical Studies: A Systematic Review. Front. Drug Discov., 2.","DOI":"10.3389\/fddsv.2022.992087"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ronner, M.N., De Kam, M.L., Van Reeuwijk, S., Burggraaf, J., Jansen, M.A.A., and Moerland, M. (2026). Neoantigen Immune Responses in Healthy Volunteers: Insights from Multiple Integrated Keyhole Limpet Hemocyanin Challenge Studies on Repeated Immunization and Response Covariates. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1717333"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.clim.2005.07.005","article-title":"Diminished Neo-Antigen Response to Keyhole Limpet Hemocyanin (KLH) Vaccines in Patients after Treatment with Chemotherapy or Hematopoietic Cell Transplantation","volume":"117","author":"Miller","year":"2005","journal-title":"Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1002\/eji.201040701","article-title":"Modulation of Systemic Antigen-Specific Immune Responses by Oral Antigen in Humans","volume":"40","author":"Kapp","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.1002\/eji.201445024","article-title":"Preexisting Antigen-specific Immune Responses Are Modulated by Oral KLH Feeding in Humans","volume":"45","author":"Hostmann","year":"2015","journal-title":"Eur. J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1634\/theoncologist.2010-0307","article-title":"Phase III Multicenter Clinical Trial of the Sialyl-TN (STn)-Keyhole Limpet Hemocyanin (KLH) Vaccine for Metastatic Breast Cancer","volume":"16","author":"Miles","year":"2011","journal-title":"Oncologist"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1007\/s00262-012-1263-z","article-title":"Humoral Anti-KLH Responses in Cancer Patients Treated with Dendritic Cell-Based Immunotherapy Are Dictated by Different Vaccination Parameters","volume":"61","author":"Aarntzen","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/prca.200900130","article-title":"Evaluation of Human Antibody Responses to Keyhole Limpet Hemocyanin (KLH) on a Carbohydrate Microarray","volume":"4","author":"Oyelaran","year":"2010","journal-title":"Proteom. Clin. Appl."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev-immunol-030409-101159","article-title":"How Bacterial Carbohydrates Influence the Adaptive Immune System","volume":"28","author":"Avci","year":"2010","journal-title":"Annu. Rev. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Micoli, F., Adamo, R., and Costantino, P. (2018). Protein Carriers for Glycoconjugate Vaccines: History, Selection Criteria, Characterization and New Trends. Molecules, 23.","DOI":"10.3390\/molecules23061451"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"103096","DOI":"10.1016\/j.xcrp.2026.103096","article-title":"Emerging Strategies for Advancing Peptide Vaccines","volume":"7","author":"Luo","year":"2026","journal-title":"Cell Rep. Phys. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41541-021-00409-1","article-title":"Combined Effects of Glycan Chain Length and Linkage Type on the Immunogenicity of Glycoconjugate Vaccines","volume":"6","author":"Anish","year":"2021","journal-title":"npj Vaccines"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1084\/jem.152.2.361","article-title":"Preparation, Characterization, and Immunogenicity of Haemophilus influenzae Type b Polysaccharide-Protein Conjugates","volume":"152","author":"Schneerson","year":"1980","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.4161\/hv.26109","article-title":"Protein Carriers of Conjugate Vaccines: Characteristics, Development, and Clinical Trials","volume":"9","author":"Pichichero","year":"2013","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1016\/j.vaccine.2017.04.078","article-title":"Polysaccharide Conjugate Vaccine Protein Carriers as a \u201cNeglected Valency\u201d\u2014Potential and Limitations","volume":"35","author":"Berti","year":"2017","journal-title":"Vaccine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.xphs.2019.10.047","article-title":"Identification of Formaldehyde-Induced Modifications in Diphtheria Toxin","volume":"109","author":"Metz","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2293","DOI":"10.1056\/NEJMoa1003812","article-title":"Immunogenicity and Safety of a Meningococcal A Conjugate Vaccine in Africans","volume":"364","author":"Sow","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1016\/S0041-0101(01)00165-9","article-title":"Understanding the Mode of Action of Diphtheria Toxin: A Perspective on Progress during the 20th Century","volume":"39","author":"Collier","year":"2001","journal-title":"Toxicon"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.ijbiomac.2022.07.137","article-title":"Cross Reacting Material (CRM197) as a Carrier Protein for Carbohydrate Conjugate Vaccines Targeted at Bacterial and Fungal Pathogens","volume":"218","author":"Khatuntseva","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.biologicals.2011.05.004","article-title":"Biochemical and Biological Characteristics of Cross-Reacting Material 197 CRM197, a Non-Toxic Mutant of Diphtheria Toxin: Use as a Conjugation Protein in Vaccines and Other Potential Clinical Applications","volume":"39","author":"Costantino","year":"2011","journal-title":"Biologicals"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1093\/nar\/12.10.4063","article-title":"The Amino-Acid Sequence of Two Non-Toxic Mutants of Diphtheria Toxin: CRM45 and CRM197","volume":"12","author":"Giannini","year":"1984","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1016\/j.vaccine.2010.06.026","article-title":"Glycoconjugate Vaccines and Immune Interference: A Review","volume":"28","author":"Dagan","year":"2010","journal-title":"Vaccine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.vaccine.2009.09.113","article-title":"Effect of Vaccination with Pneumococcal Capsular Polysaccharides Conjugated to Haemophilus influenzae-Derived Protein D on Nasopharyngeal Carriage of Streptococcus pneumoniae and H. influenzae in Children under 2 Years of Age","volume":"28","author":"Prymula","year":"2009","journal-title":"Vaccine"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1086\/527396","article-title":"Protein D of Haemophilus influenzae: A Protective Nontypeable H. Influenzae Antigen and a Carrier for Pneumococcal Conjugate Vaccines","volume":"46","author":"Forsgren","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1016\/j.vaccine.2006.09.025","article-title":"Immunogenicity of a Combination Vaccine Containing Pneumococcal Conjugates and Meningococcal PorA OMVs","volume":"25","author":"Pillai","year":"2007","journal-title":"Vaccine"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0022-3476(05)81186-2","article-title":"Differences in the Immunogenicity of Three Haemophilus influenzae Type b Conjugate Vaccines in Infants","volume":"121","author":"Granoff","year":"1992","journal-title":"J. Pediatr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1002\/1521-4141(200108)31:8<2373::AID-IMMU2373>3.0.CO;2-G","article-title":"Carrier-Mediated Enhancement of Cognate T Cell Help: The Basis for Enhanced Immunogenicity of Meningococcal Outer Membrane Protein Polysaccharide Conjugate Vaccine","volume":"31","author":"Ochs","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"16771","DOI":"10.1038\/s41598-024-67715-1","article-title":"Shrimp Hemocyanin Elicits a Potent Humoral Response in Mammals and Is Favorable to Hapten Conjugation","volume":"14","author":"Sun","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_74","first-page":"e6","article-title":"Thermal Biology and Metabolic Scope of Two Species of Juvenile Gastropod Mollusks Inhabiting Kelp Forests","volume":"64","year":"2025","journal-title":"Zool. Stud."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/d41586-021-01142-4","article-title":"Fevers Are Plaguing the Oceans\u2014And Climate Change Is Making Them Worse","volume":"593","author":"Viglione","year":"2021","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Cavanaugh, K.C., Reed, D.C., Bell, T.W., Castorani, M.C.N., and Beas-Luna, R. (2019). Spatial Variability in the Resistance and Resilience of Giant Kelp in Southern and Baja California to a Multiyear Heatwave. Front. Mar. Sci., 6.","DOI":"10.3389\/fmars.2019.00413"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1038\/s41598-018-20009-9","article-title":"Genetic Diversity and Kelp Forest Vulnerability to Climatic Stress","volume":"8","author":"Wernberg","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/s43247-021-00177-9","article-title":"Southward Decrease in the Protection of Persistent Giant Kelp Forests in the Northeast Pacific","volume":"2","author":"Cavanaugh","year":"2021","journal-title":"Commun. Earth Environ."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2021). 2021 Alzheimer\u2019s Disease Facts and Figures. Alzheimer\u2019s Dement., 17, 327\u2013406.","DOI":"10.1002\/alz.12328"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"577","DOI":"10.4103\/NRR.NRR-D-24-00846","article-title":"Recent Advances in Immunotherapy Targeting Amyloid-Beta and Tauopathies in Alzheimer\u2019s Disease","volume":"21","author":"Sha","year":"2026","journal-title":"Neural Regen. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.brainresbull.2021.05.019","article-title":"Immunization with A\u03b23-10-KLH Vaccine Improves Cognitive Function and Ameliorates Mitochondrial Dysfunction and Reduces Alzheimer\u2019s Disease-like Pathology in Tg-APPswe\/PSEN1dE9 Mice","volume":"174","author":"Zhang","year":"2021","journal-title":"Brain Res. Bull."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.bbi.2025.06.001","article-title":"A Novel A\u03b2 B-Cell Epitope Vaccine, A\u03b21-10 with Carrier Protein OVA and KLH Reduce A\u03b2-Induced Neuroinflammation Mediated Neuropathology in Mouse Model of Alzheimer\u2019s Disease","volume":"129","author":"Park","year":"2025","journal-title":"Brain Behav. Immun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S1474-4422(16)30331-3","article-title":"Safety and Immunogenicity of the Tau Vaccine AADvac1 in Patients with Alzheimer\u2019s Disease: A Randomised, Double-Blind, Placebo-Controlled, Phase 1 Trial","volume":"16","author":"Novak","year":"2017","journal-title":"Lancet Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"63","DOI":"10.14283\/jpad.2018.45","article-title":"AADvac1, an Active Immunotherapy for Alzheimer\u2019s Disease and Non Alzheimer Tauopathies: An Overview of Preclinical and Clinical Development","volume":"6","author":"Novak","year":"2019","journal-title":"J. Prev. Alzheimer\u2019s Dis."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nature01323","article-title":"Inflammation in Atherosclerosis","volume":"420","author":"Libby","year":"2002","journal-title":"Nature"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nri3520","article-title":"Macrophages in Atherosclerosis: A Dynamic Balance","volume":"13","author":"Moore","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/ni.2001","article-title":"The Immune System in Atherosclerosis","volume":"12","author":"Hansson","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1161\/01.ATV.0000178991.71605.18","article-title":"Atherosclerotic Plaque Progression and Vulnerability to Rupture","volume":"25","author":"Virmani","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1093\/eurheartj\/ehz455","article-title":"2019 ESC\/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk","volume":"41","author":"Mach","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease","volume":"377","author":"Ridker","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1161\/CIRCRESAHA.115.306656","article-title":"From CRP to IL-6 to IL-1: Moving Upstream To Identify Novel Targets for Atheroprotection","volume":"118","author":"Ridker","year":"2016","journal-title":"Circ. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1586\/erv.13.4","article-title":"Vaccines against Atherosclerosis","volume":"12","author":"Nilsson","year":"2013","journal-title":"Expert Rev. Vaccines"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1161\/CIRCRESAHA.118.313816","article-title":"Atherosclerosis: A Chronic Inflammatory Disease with an Autoimmune Component","volume":"123","author":"Kobiyama","year":"2018","journal-title":"Circ. Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1161\/CIRCULATIONAHA.122.061516","article-title":"Peptide Vaccine Against ADAMTS-7 Ameliorates Atherosclerosis and Postinjury Neointima Hyperplasia","volume":"147","author":"Ma","year":"2022","journal-title":"Circulation"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1056\/NEJMra023160","article-title":"Drug Addiction","volume":"349","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of Addiction: A Neurocircuitry Analysis","volume":"3","author":"Koob","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1146\/annurev.neuro.29.051605.113009","article-title":"NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory","volume":"29","author":"Hyman","year":"2006","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-801284-0.00001-4","article-title":"Neuroimmune Mechanisms of Alcohol and Drug Addiction","volume":"Volume 118","author":"Cui","year":"2014","journal-title":"International Review of Neurobiology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.neuropharm.2013.04.004","article-title":"Epigenetic Mechanisms of Drug Addiction","volume":"76","author":"Nestler","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_100","unstructured":"U.S. Department of Health and Human Services (2008). Treating Tobacco Use and Dependence: 2008 Update."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1151\/spp021113","article-title":"The Neurobiology of Opioid Dependence: Implications for Treatment","volume":"1","author":"Kosten","year":"2002","journal-title":"Sci. Pract. Perspect."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Lu, T., Li, X., Zheng, W., Kuang, C., Wu, B., Liu, X., Xue, Y., Shi, J., Lu, L., and Han, Y. (2024). Vaccines to Treat Substance Use Disorders: Current Status and Future Directions. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16010084"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/clpt.2011.281","article-title":"Vaccines Against Drug Abuse","volume":"91","author":"Shen","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1177\/10915818251355948","article-title":"Safety and Toxicological Evaluation of Subunit Keyhole Limpet Hemocyanin-Loaded Lipid\u2013PLGA Hybrid Nanoparticles (sKLH-hNPs) as a Nanocarrier for an Opioid Use Disorder Vaccine","volume":"44","author":"Walter","year":"2025","journal-title":"Int. J. Toxicol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.bmcl.2012.12.048","article-title":"Enhancing Nicotine Vaccine Immunogenicity with Liposomes","volume":"23","author":"Lockner","year":"2013","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1016\/j.vaccine.2013.04.027","article-title":"Liposomes Containing Monophosphoryl Lipid A: A Potent Adjuvant System for Inducing Antibodies to Heroin Hapten Analogs","volume":"31","author":"Matyas","year":"2013","journal-title":"Vaccine"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.nano.2016.07.015","article-title":"A Nanoparticle-Based Nicotine Vaccine and the Influence of Particle Size on Its Immunogenicity and Efficacy","volume":"13","author":"Zhao","year":"2017","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1021\/acschembio.6b00977","article-title":"An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life","volume":"12","author":"Kimishima","year":"2017","journal-title":"ACS Chem. Biol."},{"key":"ref_109","unstructured":"Comer, S.D. (2026). Phase 1A\/1B Clinical Trials of Multivalent Opioid Vaccine Components."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Rosenglick, N., Valentin, G., Marineni, K., Neto, E.P., and Andreana, P.R. (2026). Conjugate Vaccines Targeting Tumor-Associated Carbohydrate Antigens. Vaccines, 14.","DOI":"10.3390\/vaccines14040287"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"137","DOI":"10.4161\/hv.2941","article-title":"Cancer Vaccines Targeting Carbohydrate Antigens","volume":"2","author":"Livingston","year":"2006","journal-title":"Hum. Vaccines"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"3401","DOI":"10.1172\/JCI80009","article-title":"Therapeutic Cancer Vaccines","volume":"125","author":"Melief","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s41568-021-00346-0","article-title":"Therapeutic Cancer Vaccines","volume":"21","author":"Saxena","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3892\/ol.2024.14400","article-title":"Perfusion Drugs for Non-muscle Invasive Bladder Cancer (Review)","volume":"27","author":"Qian","year":"2024","journal-title":"Oncol. Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1200\/JCO.2011.39.2936","article-title":"Intracutaneous and Intravesical Immunotherapy with Keyhole Limpet Hemocyanin Compared with Intravesical Mitomycin in Patients with Non\u2013Muscle-Invasive Bladder Cancer: Results From a Prospective Randomized Phase III Trial","volume":"30","author":"Lammers","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"e70017","DOI":"10.1002\/ijch.70017","article-title":"Carbohydrate-Based Drug Discovery: Synthetic Strategies and Clinical Applications","volume":"66","author":"Scheeff","year":"2026","journal-title":"Isr. J. Chem."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.eururo.2011.07.010","article-title":"Smoking Status Is a Risk Factor for Recurrence After Transurethral Resection of Non\u2013Muscle-Invasive Bladder Cancer","volume":"60","author":"Lammers","year":"2011","journal-title":"Eur. Urol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrclinonc.2017.43","article-title":"Targeted Agents and Immunotherapies: Optimizing Outcomes in Melanoma","volume":"14","author":"Luke","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of Mutational Processes in Human Cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1126\/science.aar4060","article-title":"Cancer Immunotherapy Using Checkpoint Blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.4049\/jimmunol.1490019","article-title":"IL-2: The First Effective Immunotherapy for Human Cancer","volume":"192","author":"Rosenberg","year":"2014","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved Survival with Ipilimumab in Patients with Metastatic Melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1200\/JCO.1994.12.5.1036","article-title":"Improved Survival in Stage III Melanoma Patients with GM2 Antibodies: A Randomized Trial of Adjuvant Vaccination with GM2 Ganglioside","volume":"12","author":"Livingston","year":"1994","journal-title":"J. Clin. Oncol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"B4","DOI":"10.1016\/j.vaccine.2007.06.033","article-title":"Vaccine Therapy for Melanoma: Current Status and Future Directions","volume":"25","author":"Terando","year":"2007","journal-title":"Vaccine"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/(SICI)1097-0215(20000301)85:5<659::AID-IJC11>3.0.CO;2-5","article-title":"Induction of Antibodies against GD3 Ganglioside in Melanoma Patients by Vaccination with GD3-Lactone-KLH Conjugate plus Immunological Adjuvant QS-21","volume":"85","author":"Ragupathi","year":"2000","journal-title":"Int. J. Cancer"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"117687","DOI":"10.1016\/j.bcp.2026.117687","article-title":"Advances in Melanoma Immunotherapy: Harnessing Vaccination as a Potential Novel Immunotherapeutic Strategy","volume":"245","author":"Abuelainain","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3831","DOI":"10.1200\/JCO.2012.47.9303","article-title":"Adjuvant Ganglioside GM2-KLH\/QS-21 Vaccination versus Observation after Resection of Primary Tumor > 1.5 Mm in Patients with Stage II Melanoma: Results of the EORTC 18961 Randomized Phase III Trial","volume":"31","author":"Eggermont","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"4717","DOI":"10.1158\/1078-0432.CCR-04-0345","article-title":"Sequential Immunization of Melanoma Patients with GD3 Ganglioside Vaccine and Anti-Idiotypic Monoclonal Antibody That Mimics GD3 Ganglioside","volume":"10","author":"Chapman","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1158\/2326-6066.CIR-19-0401","article-title":"pVACtools: A Computational Toolkit to Identify and Visualize Cancer Neoantigens","volume":"8","author":"Hundal","year":"2020","journal-title":"Cancer Immunol. Res."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Kumar, A., Dixit, S., Srinivasan, K., M, D., and Vincent, P.M.D.R. (2024). Personalized Cancer Vaccine Design Using AI-Powered Technologies. Front. 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