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309 Memory Responses Are Present in Mucosal and Systemic Compartments after Mucosal (Intranasal) Immunization with Nonreplicating Antigen
S. E. Pacheco*, M. C. Hart, and P. R. Rogers
Baylor Coll. of Med., Houston, TX
Background: Mucosal immunity and immunological memory are required for protection against pathogens acquired through mucosal tissues. This is the case for HIV, a pathogen acquired primarily through the genital and gastrointestinal tracts. In general, systemic immunization is an inefficient approach to induce strong, long-lasting mucosal immunity. We present data demonstrating that antigen-specific, long-lasting immunity can be induced by intranasal delivery of nonreplicating antigen and mucosal adjuvant.
Methods: Groups of 8- to 12-week-old C3H/HeJ mice were immunized with soluble HIV reverse transcriptase (RT, 2.5 mug/ml) in the presence or absence of the mucosal adjuvant cholera toxin (CT, 1µg/ml). Animals received 3 immunizations, 1 week apart, and were sacrificed 1 to 2 weeks after immunization or >2 months after immunization. Lymphoid cells from various mucosal (e.g., salivary gland-associated lymph nodes [l.n.], mesenteric l.n.) and systemic (e.g., spleen, axillary l.n., inguinal l.n.) compartments were stimulated in vitro with RT. Cells were analyzed for RT-specific in vitro proliferation, secretion of interferon gamma (IFNgamma) and IL4 in stimulated culture supernatants (ELISA) and cytokine secreting cells (ELISPOT).
Results: Statistically significant RT-specific proliferative responses were present in all mucosal or systemic compartments tested 1 to 2 weeks following initial immunization. These responses were also present in the same compartments from animal samples analyzed >2 months after completion of the immunization series. Both IL4 and IFNgamma were detected in stimulated culture supernatants from both groups. Preliminary ELISPOT assays revealed the presence of IFNgamma and IL4 spot-forming cells in the spleen and mesenteric l.n. from animals sacrificed >2 months after completion of the immunization series (up to 1 year).
Conclusions: Mucosal immunization by the intranasal route induces antigen-specific memory immune responses in multiple systemic and mucosal immune compartments after delivery of nonreplicating antigen and adjuvant. This strategy must be considered when designing vaccines against HIV.
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