Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 41, Issue 9, Pages 2642-2653Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.201041297
Keywords
Adjuvants; CD4(+) T cells; Mucosal immunity; Vaccination
Categories
Funding
- Swedish Foundation for Strategic Research-The Mucosal Immunobiology and Vaccine Center (MIVAC)
- Swedish Research Council
- Swedish Cancer Foundation
- Sahlgrenska University Hospital Foundation
- EU [QLK2-CT-2001-01702, QLK2-CT-199-00228, LSHP-CT-2003-503240]
- SAREC
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Immunizations via the i.n. and intravaginal (ivag) routes effectively generate strong genital tract antibody-mediated immunity. To what extent the same is true for T-cell responses is incompletely known. Therefore, we set out to investigate optimal conditions for stimulation of genital tract CD4(+) T-cell responses, using adoptive transfer of mouse DO11.10 TCR transgenic T cells specific for OVA and OVA conjugated to cholera toxin (CT) as an immunogen. We observed that progesterone was required for a T-cell response following ivag immunization, whereas estradiol prevented a response. Although i.n. immunization stimulated OVA-specific CD4(+) T-cell responses in the draining LNs, it was substantially less effective compared to ivag. More importantly, an ivag booster immunization was absolutely required to attract T cells to the genital tract mucosa itself. While clinical use of CT is precluded because of its toxicity, we developed a combined adjuvant vector based on a non-toxic derivative of CT and immune-stimulating complexes. The CTA1-DD/immune-stimulating complexes (ISCOMs) adjuvant together with major outer membrane protein was effective at stimulating genital tract CD4(+) T-cell immunity and protection against a live chlamydial infection, which holds promise for the development of mucosal vaccines against sexually transmitted infections.
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