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Etx B subunit Adjuvant |
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Vaxjo ID |
17 |
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Vaccine Adjuvant Name |
Etx B subunit Adjuvant |
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Adjuvant VO ID |
VO_0001272
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Description |
The non-toxic B subunit of Escherichia coli heat labile enterotoxin(EtxB) is a potent nasal adjuvant; however, its usefulness following oral delivery is unconfirmed. Data suggests that although EtxB is a weak oral adjuvant, it can profoundly modulate the nature of the immune response to admixed antigen (Plant et al., 2003). |
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Stage of Development |
Clinical Trial |
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Dosage |
BALB/c mice [high responder to EtxB] of age 7-12 weeks (Charles River Breeding Laboratories) were used in a study. Antibody responses to EtxB or EtxB(G33D) were measured after subcutaneous injection of mice with 30 µg of protein in PBS, followed by a booster injection 10 days later. Other mice were given the same protein dose orally in sodium bicarbonate (50 mg/ml) weekly on three occasions. Control mice were given PBS. For proliferative assays, mice were injected intraperitoneally with 30 µg of either EtxB or EtxB(G33D) in complete Freund's adjuvant 10 days prior to lymph node isolation (Nashar et al., 1996). |
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Function |
EtxB profoundly modulated the nature of the response to subsequent parenteral challenge, promoting IgG1 in favor of IgG2a antibodies and depressing IFN-gamma production while elevating TGF-beta secretion. The addition of EtxB promoted T cell division, as assessed by loss of staining with carboxyfluorescein diacetate succinimidyl ester. According to a study, enhanced cell division promoted by EtxB was associated with T cell differentiation (increased numbers of CD45RBlow cells) in vivo (Plant et al., 2003). |
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Safety |
These studies have highlighted the potential of the B subunit of Etx as a safe and effective adjuvant capable of triggering mucosal and systemic immunity. The findings should allow the development of mucosal vaccination strategies in the absence of residual toxicity associated with the use of holotoxins or their mutants. However, the finding that the immune response triggered by EtxB is Th2 dominated indicates that careful consideration is necessary in determining whether it is suitable for use in vaccines against individual infectious agents (Richards et al., 2001). |
| Related Vaccine(s) |
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| References |
Nashar et al., 1996: Nashar TO, Webb HM, Eaglestone S, Williams NA, Hirst TR. Potent immunogenicity of the B subunits of Escherichia coli heat-labile enterotoxin: receptor binding is essential and induces differential modulation of lymphocyte subsets. Proceedings of the National Academy of Sciences of the United States of America. 1996; 93(1); 226-230. [PubMed: 8552610].
Plant et al., 2003: Plant A, Williams R, Jackson ME, Williams NA. The B subunit of Escherichia coli heat labile enterotoxin abrogates oral tolerance, promoting predominantly Th2-type immune responses. European journal of immunology. 2003; 33(11); 3186-3195. [PubMed: 14579287].
Richards et al., 2001: Richards CM, Aman AT, Hirst TR, Hill TJ, Williams NA. Protective mucosal immunity to ocular herpes simplex virus type 1 infection in mice by using Escherichia coli heat-labile enterotoxin B subunit as an adjuvant. Journal of virology. 2001; 75(4); 1664-1671. [PubMed: 11160664].
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