Abstract
The selection of any specific immunization route is critical when defining future vaccine strategies against a genital infection like Chlamydia trachomatis (C.t.). An optimal Chlamydia vaccine needs to elicit mucosal immunity comprising both neutralizing IgA/IgG antibodies and strong Th1/Th17 responses. A strategic tool to modulate this immune profile and mucosal localization of vaccine responses is to combine parenteral and mucosal immunizations routes. In this study, we investigate whether this strategy can be adapted into a two-visit strategy by simultaneous subcutaneous (SC) and nasal immunization. Using a subunit vaccine composed of C.t. antigens (Ags) adjuvanted with CAF01, a Th1/Th17 promoting adjuvant, we comparatively evaluated Ag-specific B and T cell responses and efficacy in mice following SC and simultaneous SC and nasal immunization (SIM). We found similar peripheral responses with regard to interferon gamma and IL-17 producing Ag-specific splenocytes and IgG serum levels in both vaccine strategies but in addition, the SIM protocol also led to Ag-specific IgA responses and increased B and CD4+ T cells in the lung parenchyma, and in lower numbers also in the genital tract (GT). Following vaginal infection with C.t., we observed that SIM immunization gave rise to an early IgA response and IgA-secreting plasma cells in the GT in contrast to SC immunization, but we were not able to detect more rapid recruitment of mucosal T cells. Interestingly, although SIM vaccination in general improved mucosal immunity we observed no improved efficacy against genital infection compared to SC, a finding that warrants for further investigation. In conclusion, we demonstrate a novel vaccination strategy that combines systemic and mucosal immunity in a two-visit strategy.
Highlights
Chlamydia trachomatis (C.t.) is the leading cause of bacterial sexually transmitted diseases worldwide
The aim was to investigate whether it was possible to elicit Chlamydia-specific T cell and Ab (IgA) responses in the genital tract (GT) by administering a Chlamydia vaccine simultaneously, by the SC and IN routes. It was evaluated how this immunization strategy would affect both the peripheral Th1/Th17 and mucosal IgA responses compared to separate SC followed by IN immunization. We showed that the latter immunization strategy resulted in high peripheral Th17 responses, which following nasal boost were pulled to the lungs and facilitated induction of mucosal IgA [31]
Equal levels of Ag-specific IgG1 were measured in serum and lungs of all the immunized groups (Figures 1C,D), while significantly higher Ag-specific IgA responses were induced in the SIM- and PB-immunized mice compared to the SC immunized (Figures 1E,F), confirming that mucosal immunization favors the generation of IgA Abs
Summary
Chlamydia trachomatis (C.t.) is the leading cause of bacterial sexually transmitted diseases worldwide. The choice of immunization routes is critical when defining future vaccine strategies against a genital infection like Chlamydia. It is widely believed that an optimal Chlamydia vaccine will need to elicit mucosal immunity comprising both neutralizing antibodies (Abs) and cell-mediated immunity [2,3,4,5,6,7,8]. In the vagino-cervix of humans, IgG is the predominant secreted isotype relative to secretory IgA (SIgA) [22]. Th17 cells have been recognized as a key accelerator of mucosal immunity and IgA secretion [27, 28]. Th17 cells display a great degree of plasticity, capable of acquiring functional characteristics of follicular helper T cells, which can induce IgA-isotype switching [29,30,31]
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