No 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.

No abstract

Monocytes are one of the major phagocytic cells in the periphery that patrols the circulation for invading pathogens, and upon activation differentiates into dendritic cells, capable of migration to lymph nodes eliciting an adaptive immune response. Monocytes has for more than a decade been precursor cell for generation of autologous dendritic cell cancer vaccines, but clinical results have shown limiting benefits for the patients. One way of improving dendritic cell vaccines is targeting the monocytes in vivo with a suitable carrier of adjuvant together with tumor antigens, to boost monocyte differentiation towards tumor antigen presenting DCs. Here we report a novel monocyte targeting liposome technology capable of delivering TLR7 agonist to CD14 positive monocytes in fresh whole human blood. Liposomes with a positive surface charge were able to specifically target monocytes over lymphocytes and granulocytes, and showed association with 90-100 % of the monocytes. Formulation of the TLR7 agonist in monocyte targeting liposomes showed strong activation of the monocytes, with potent induction of proinflammatory cytokines, and differentiation into tissue inflammatory DCs, demonstrating that the liposomes are able to deliver compounds to the endosomes where TLR7 is present. The present monocyte targeting technology may be a promising approach for designing cancer vaccines with suitable adjuvants and cancer antigens.