Tetanus vaccination related to the decline of trachoma in the Western World? Anti-tetanus antibodies confer partial protection against ocular chlamydial infection.

Abstract

Purpose : Trachoma was once endemic in Europe and the United States and disappeared even before the antibiotic era. Interestingly, the decline of trachoma incidence parallels the introduction of mandatory vaccination against tetanus. The aim of this study was to evaluate whether antibodies generated by immunization with tetanus toxoid (TTd) are cross-reactive with chlamydial protein antigens and to investigate if they confer any protection against ocular chlamydial infection in guinea pigs.

Methods : Two well-characterized murine anti-tetanus monoclonal antibodies, MAb26 and MAb51, were used. MAb26 binds tetanus toxin (TTx) with low affinity and is not able to confer protection against TTx, while MAb51 possesses high affinity for TTx and protects mice from TTx intoxication. MAb26 and MAb51 were assessed for binding to Chlamydia caviae in direct and inhibitory ELISAs. Western blot was done for recognition of C. caviae protein antigens. MAbs capability to prevent chlamydial infection was assessed: i) in vitro using a neutralization assay based on human conjunctival epithelial (HCjE) cells infected with 1x10⁵ IFU of C. trachomatis serovar B (CtB) and ii) in vivo using a guinea pig model of C. caviae ocular infection (1x10⁴ IFU/eye).

Results : Direct ELISA revealed significantly higher binding of MAb26 to C. caviae compared to MAb51. The binding of MAb26 to TTd was more profoundly inhibited with preincubation with C. caviae than the binding of MAb51. Western blot analyses confirmed the reactivity of MAb26 and MAb51 with chlamydial proteins, especially those having molecular weights below 50 kDa. MAb26 was more efficient than MAb51 in prevention of HCjE cells infection. MAb26 conferred ~40% inhibition while in the presence of MAb51 the inhibition was less than 5%. Finally, MAb26 significantly diminished intensity of ocular pathology in guinea pigs infected with C. caviae in comparison with either MAb51-treated guinea pigs or sham-control.

Conclusions : TTd immunization promotes secretion of TTd-specific antibodies, which are not capable to confer protection against TTx intoxication but, due to cross-reactivity, improve immunity to heterologous antigens.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.