Sublingual Boosting with a Novel Mucoadhesive Thermogelling Hydrogel Following Parenteral CAF01 Priming as a Strategy Against Chlamydia trachomatis

• Published in: Advanced healthcare materials Vol. 11; no. 11; pp. e2102508 - n/a
• Main Authors: Garcia‐del Rio, Lorena, Diaz‐Rodriguez, Patricia, Pedersen, Gabriel Kristian, Christensen, Dennis, Landin, Mariana
• Format: Journal Article
• Language: English
• Published: Germany 01.06.2022
• Subjects: Adjuvants, Immunologic; Administration, Sublingual; Animals; Artificial Intelligence; cationic adjuvant liposomes; Chlamydia trachomatis; Hydrogels - pharmacology; Mice; Mice, Inbred BALB C; mucoadhesive and thermosensitive platforms; mucosal vaccination; polymeric networks; prime‐boost strategy; systemic and sublingual immunization; mucosal vaccination; mucoadhesive and thermosensitive platforms; polymeric networks; prime-boost strategy; systemic and sublingual immunization; cationic adjuvant liposomes
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202102508

Chlamydia trachomatis is the most prevalent sexually transmitted disease of bacterial origin. The high number of asymptomatic cases makes it difficult to stop the transmission, requiring vaccine development. Herein, a strategy is proposed to obtain local genital tract immunity against C. trachomatis through parenteral prime and sublingual boost. Subcutaneous administration of chlamydia CTH522 subunit vaccine loaded in the adjuvant CAF01 is combined with sublingual administration of CTH522 loaded in a novel thermosensitive and mucoadhesive hydrogel. Briefly, a ternary optimized hydrogel (OGEL) with desirable biological and physicochemical properties is obtained using artificial intelligence techniques. This formulation exhibits a high gel strength and a strong mucoadhesive, adhesive and cohesive nature. The thermosensitive properties of the hydrogel facilitate application under the tongue. Meanwhile the fast gelation at body temperature together with rapid antigen release should avoid CTH522 leakage by swallowing and increase the contact with sublingual tissue, thus promoting absorption. In vivo studies demonstrate that parenteral‐sublingual prime‐boost immunization, using CAF01 and OGEL as CTH522 vaccine carriers, shows a tendency to increase cellular (Th1/Th17) immune responses when compared to mucosal or parenteral vaccination alone. Furthermore, parenteral prime with CAF01/CTH522 followed by sublingual boosting with OGEL/CTH522 elicits a local IgA response in the genital tract. The optimal thermosensitive, mucoadhesive and stable hydrogel (OGEL) developed through artificial intelligence tools within the concept of “Quality by Design” is useful as a carrier for chlamydia subunit vaccine CTH522. The sublingual administration of OGEL/CTH522, after parenteral immunization with CAF01/CTH522 (cationic liposomes), promotes Th1&Th17 immune responses in a mouse model and elicit local IgA response in the genital tract.