The combined CTA1-DD/ISCOM adjuvant vector promotes priming of mucosal and systemic immunity to incorporated antigens by specific targeting of B cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Anja HelgebyNils Lycke

Abstract

The cholera toxin A1 (CTA1)-DD/QuilA-containing, immune-stimulating complex (ISCOM) vector is a rationally designed mucosal adjuvant that greatly potentiates humoral and cellular immune responses. It was developed to incorporate the distinctive properties of either adjuvant alone in a combination that exerted additive enhancing effects on mucosal immune responses. In this study we demonstrate that CTA1-DD and an unrelated Ag can be incorporated together into the ISCOM, resulting in greatly augmented immunogenicity of the Ag. To demonstrate its relevance for protection against infectious diseases, we tested the vector incorporating PR8 Ag from the influenza virus. After intranasal immunization we found that the immunogenicity of the PR8 proteins were significantly augmented by a mechanism that was enzyme dependent, because the presence of the enzymatically inactive CTA1R7K-DD mutant largely failed to enhance the response over that seen with ISCOMs alone. The combined vector was a highly effective enhancer of a broad range of immune responses, including specific serum Abs and balanced Th1 and Th2 CD4(+) T cell priming as well as a strong mucosal IgA response. Unlike unmodified ISCOMs, Ag incorporated into the combined vector coul...Continue Reading

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Citations

Feb 27, 2007·Journal of Zhejiang University. Science. B·Zahid Iqbal RajputAbdullah G Arijo
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