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

Abstract

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.

Recent advances in conductive hydrogels: classifications, properties, and applications

“…The tongue is one of the most sensitive, soft and flexible body parts that possesses many kinds of receptors, like mechanical receptors, taste receptors. 228,[272][273][274][275] Secreted saliva, which consists of 99% water and a small number of electrolytes and proteins, can keep the surface of the tongue moist. 276 Saliva plays the role of dissolving tastants and accelerate their passage through ion channels.…”

Advances in Chlamydia trachomatis Vaccination: Unveiling the Potential of Major Outer Membrane Protein Derivative Constructs

“…IgG that had transudated into the vagina of minipigs after intramuscular vaccination contributed to their protection against C. trachomatis [ 35 ]. The urogenital tract is more permeable to the transudation of serum antibodies than other mucosae [ 36 ]. Thus, both vaginal IgG and (s)IgA seem to have protective potential for genital C. trachomatis infections [ 24 ].…”

“…Therefore, alternative mucosal immunization sites like gut-, nasal-, or bronchus-associated lymphoid tissue (GALT, NALT and BALT) could be considered in C. trachomatis vaccination strategies, as certain inductive and effector sites of the common mucosal immune system effectively interact [ 28 , 37 ]. Moreover, GT vaccination depends on the host hormonal status [ 36 ]. This interaction between mucosal sites is also interesting for the development of not only genital but intestinal mucosal immunity as well, since C. trachomatis persistence in the GI tract occurs [ 13 , 38 ].…”

“…Protection was CD4 + T cell- but not MOMP-conformation-dependent [ 76 ]. Combining several delivery systems or adjuvants to induce a more diverse immune response has also been a research topic [ 27 , 34 , 36 , 38 , 77 ].…”

Overexpression of the Bam Complex Improves the Production of Chlamydia trachomatis MOMP in the E. coli Outer Membrane

“…E. coli BL21(DE3), Clearcoli(DE3) (Novagen, Darmstadt, Germany) and Salmonella enterica serovar Typhimurium SL3261-∆msbB strains were applied for protein expression experiments. The latter strain was created by allelic exchange through double cross-over homologous recombination as described [61] using S. Typhimurium SL3261 [62] as the parental strain. DH5α and BL21(DE3) were cultured in lysogeny broth (LB; 10 g/L bacto tryptone, 5 g/L bacto yeast extract, 10 g/L NaCl) containing 0.2% glycerol at 37 • C. Clearcoli(DE3) was grown in the same medium supplemented with 1 mM MgSO 4 SL3261-∆msbB was cultured in TYMC (10 g/L tryptone, 5 g/L yeast extract, 2 mM MgSO 4 , 2 mM CaCl 2 ) containing 0.2% glycerol at 30 • C. Chloramphenicol (30 µg/mL) and ampicillin (100 µg/mL) antibiotics were added for plasmid maintenance, when required.…”