{"doi":"10.1371/journal.pone.0069678","title":"LT-IIb(T13I), a Non-Toxic Type II Heat-Labile Enterotoxin, Augments the Capacity of a Ricin Toxin Subunit Vaccine to Evoke Neutralizing Antibodies and Protective Immunity","abstract":"Currently, there is a shortage of adjuvants that can be employed with protein subunit vaccines to enhance protection against biological threats. LT-IIb(T13I) is an engineered nontoxic derivative of LT-IIb, a member of the type II subfamily of heat labile enterotoxins expressed by Escherichia coli, that possesses potent mucosal adjuvant properties. In this study we evaluated the capacity of LT-IIb(T13I) to augment the potency of RiVax, a recombinant ricin toxin A subunit vaccine, when co-administered to mice via the intradermal (i.d.) and intranasal (i.n.) routes. We report that co-administration of RiVax with LT-IIb(T13I) by the i.d. route enhanced the levels of RiVax-specific serum IgG antibodies (Ab) and elevated the ratio of ricin-neutralizing to non-neutralizing Ab, as compared to RiVax alone. Protection against a lethal ricin challenge was also augmented by LT-IIb(T13I). While local inflammatory responses elicited by LT-IIb(T13I) were comparable to those elicited by aluminum salts (Imject®), LT-IIb(T13I) was more effective than aluminum salts at augmenting production of RiVax-specific serum IgG. Finally, i.n. administration of RiVax with LT-IIb(T13I) also increased levels of RiVax-specific serum and mucosal Ab and enhanced protection against ricin challenge. Collectively, these data highlight the potential of LT-IIb(T13I) as an effective next-generation i.d., or possibly i.n. adjuvant for enhancing the immunogenicity of subunit vaccines for biodefense.","journal":"PLoS ONE","year":2013,"id":4519,"datarank":0.41588830833596724,"base_score":2.772588722239781,"endowment":2.772588722239781,"self_citation_contribution":0.41588830833596724,"citation_network_contribution":0.0,"self_endowment_contribution":0.41588830833596724,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":15,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2013-08-02","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":45730,"name":"Chrystal M. Chadwick","orcid":null,"position":1,"is_corresponding":false},{"id":45731,"name":"Lorrie M. Mandell","orcid":null,"position":2,"is_corresponding":false},{"id":45732,"name":"John C. Hu","orcid":"0000-0001-7632-6996","position":3,"is_corresponding":false},{"id":45733,"name":"Joanne M. O’Hara","orcid":null,"position":4,"is_corresponding":false},{"id":45734,"name":"Robert N. Brey","orcid":null,"position":5,"is_corresponding":false},{"id":45735,"name":"Nicholas J. Mantis","orcid":"0000-0002-5083-8640","position":6,"is_corresponding":false},{"id":45736,"name":"Terry D. Connell","orcid":null,"position":7,"is_corresponding":false},{"id":308,"name":"Casey S. Greene","orcid":"0000-0001-8713-9213","position":8,"is_corresponding":false},{"id":45737,"name":"Chrystal Chadwick","orcid":"0000-0001-6355-5677","position":9,"is_corresponding":false},{"id":45738,"name":"Lorrie Mandell","orcid":null,"position":10,"is_corresponding":false},{"id":45739,"name":"John W. Connell","orcid":"0000-0002-2676-8363","position":11,"is_corresponding":false}],"reference_count":42,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}