Abstract
Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world’s leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1–893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/c mice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocular mucosa was well tolerated without signs of inflammation. N-PmpC-specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFNγ immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage.
Highlights
Trachoma is the most common cause of preventable blindness in underdeveloped countries
Mucosal IgA values in mice that were subcutaneously immunized with N-polymorphic membrane protein C (PmpC) E. coli Nissle1917 (EcN) bacterial ghosts (BGs) or with Escherichia coli Nissle bacterial ghosts (EcN BGs) were comparable to those observed in control mice (Fig 2)
N-PmpC-specific serum IgA levels recorded for sera of N-PmpC EcN BGs conjunctivally and subcutaneously immunized mice were comparable to the levels recorded for the nonimmunized group (Fig 3)
Summary
Trachoma is the most common cause of preventable blindness in underdeveloped countries. Ocular disease is primarily caused by an acute inflammatory response elicited by the infection of the host cell and the T cell response to Chlamydia trachomatis (Ct). The delivery of vaccines via the ocular conjunctiva may be an attractive option for mucosal immunization against ocular pathogens as it could induce a first line of defense at the ocular surface against several disorders that cause blindness (e.g., trachoma, herpes corneae, and acanthamoeba keratitis). Ocular mucosa possesses features for generating a specific immune response in the conjunctiva-associated lymphoid tissue (CALT). CALT is assumed to play a key role in protection of the ocular surface by initiating and regulating immune responses [16]
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