ArticleThe Journal of experimental medicine1998
Mucosal adjuvanticity and immunogenicity of LTR72, a novel mutant of Escherichia coli heat-labile enterotoxin with partial knockout of ADP-ribosyltransferase activity.
Article in The Journal of experimental medicine, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 263 citations in OpenAlex.
- Review
- Immunogenicity and Reactogenicity in Q Fever Vaccine Development.Frontiers in immunology · 2022Review
- A comparative study of adjuvants effects on neonatal plasma cell survival niche in bone marrow and persistence of humoral immune responses.Frontiers in immunology · 2022Article
- Recombinant BCG expressing the LTAK63 adjuvant induces increased early and long-term immune responses against Mycobacteria.Human vaccines & immunotherapeutics · 2020Article
- LT-K63 Enhances B Cell Activation and Survival Factors in Neonatal Mice That Translates Into Long-Lived Humoral Immunity.Frontiers in immunology · 2020Article
- Review of Newly Identified Functions Associated With the Heat-Labile Toxin of EnterotoxigenicFrontiers in cellular and infection microbiology · 2019Review
- Adjuvants Enhance the Induction of Germinal Center and Antibody Secreting Cells in Spleen and Their Persistence in Bone Marrow of Neonatal Mice.Frontiers in immunology · 2019Article
- Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein.Frontiers in immunology · 2017Article
- Roles and relevance of mast cells in infection and vaccination.Journal of biomedical research · 2016Review
- The catalytic A1 domains of cholera toxin and heat-labile enterotoxin are potent DNA adjuvants that evoke mixed Th1/Th17 cellular immune responses.Human vaccines & immunotherapeutics · 2015Article
- Article
- Mechanisms of Cholera Toxin in the Modulation of TH17 Responses.Critical reviews in immunology · 2015Review
- Parenteral Adjuvant Effects of an Enterotoxigenic Escherichia coli Natural Heat-Labile Toxin Variant.Frontiers in immunology · 2014Article
- Escherichia coli heat-labile detoxified enterotoxin modulates dendritic cell function and attenuates allergic airway inflammation.PloS one · 2014Article
- Article
- The adjuvant LT-K63 can restore delayed maturation of follicular dendritic cells and poor persistence of both protein- and polysaccharide-specific antibody-secreting cells in neonatal mice.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- M cell-targeted mucosal vaccine strategies.Current topics in microbiology and immunology · 2012Review
- Side-by-side comparison of gene-based smallpox vaccine with MVA in nonhuman primates.PloS one · 2012Article
- Use of inactivated Escherichia coli enterotoxins to enhance respiratory mucosal adjuvanticity during vaccination in swine.Clinical and vaccine immunology : CVI · 2011Article
- Adjuvant activity of the catalytic A1 domain of cholera toxin for retroviral antigens delivered by GeneGun.Clinical and vaccine immunology : CVI · 2011Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat-labile Escherichia coli enterotoxin (LT) has the innate property of being a strong mucosal immunogen and adjuvant. In the attempt to reduce toxicity and maintain the useful immunological properties, several LT mutants have been produced. Some of these are promising mucosal adjuvants. However, so far, only those that were still toxic maintained full adjuvanticity. In this paper we describe a novel LT mutant with greatly reduced toxicity that maintains most of the adjuvanticity. The new mutant (LTR72), that contains a substitution Ala --> Arg in position 72 of the A subunit, showed only 0.6% of the LT enzymatic activity, was 100,000-fold less toxic than wild-type LT in Y1 cells in vitro, and was at least 20 times less effective than wild-type LT in the rabbit ileal loop assay in vivo. At a dose of 1 microg, LTR72 exhibited a mucosal adjuvanticity, similar to that observed with wild-type LT, better than that induced by the nontoxic, enzymatically inactive LTK63 mutant, and much greater than that of the recombinant B subunit. This trend was consistent for both the amounts and kinetics of the antibody induced, and priming of antigen-specific T lymphocytes. The data suggest that the innate high adjuvanticity of LT derives from the independent contribution of the nontoxic AB complex and the enzymatic activity. LTR72 optimizes the use of both properties: the enzymatic activity for which traces are enough, and the nontoxic AB complex, the effect of which is dose dependent. In fact, in dose-response experiments in mice, 20 microg of LTR72 were a stronger mucosal adjuvant than wild-type LT. This suggests that LTR72 may be an excellent candidate to be tested in clinical trials.
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