A Systems Serology Approach to the Investigation of Infection-Induced Antibody Responses and Protection in Trachoma

Background: Ocular infections with Chlamydia trachomatis serovars A-C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long term sequelae such as scarring and blindness. Here we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection. Methods: Sera from children in five trachoma endemic villages in The Gambia were assayed for 23 antibody features: IgG responses towards two Chlamydia trachomatis antigens and three serovars (elementary bodies and major outer membrane protein MOMP, serovars A-C), IgG responses towards five MOMP peptides (serovars A-C), neutralization and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected. Results: The antibody features assayed were not associated with resistance to infection (false discovery rate < 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (p < 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%). Conclusions: Systemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. This may be due to confounding factors increasing both past and future exposure to C. trachomatis, or antibody-dependent enhancement. Ocular responses, IgA, avidity or cell-mediated responses may play a greater role in protective immunity than systemic IgG. ### Competing Interest Statement The authors have declared no competing interest.