A systems serology approach to the investigation of infection-induced antibody responses and protection in trachoma

Abstract

BackgroundOcular 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.MethodsSera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two C. 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.ResultsThe 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%).ConclusionsSystemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG.

Genomic insights into local-scale evolution of ocular Chlamydia trachomatis strains within and between individuals in Gambian trachoma-endemic villages

“…We generated genetic data from 11 SvA and 30 SvB variants collected from four villages in two administrative regions on opposing sides of the river Gambia to elucidate: (i) the factors driving the diversification of ocular Ct strains; (ii) disparities in mutation frequency and accumulation profiles; (iii) selective pressures between SvA and SvB; and (iv) the dynamics of mutation accumulation within the Gambian ocular Ct-positive population over a short timeframe. This study was done in the context of an investigation of Ct infection-induced immune responses and protection in trachoma [29,30], with Ct molecular diagnosis and ompA sequencing the priority for the extracted DNA [31][32][33]. Nevertheless, an opportunistic selection of samples from this prospective cohort study allowed us to analyse Ct genomes from individuals who repeatedly tested positive over the study period, and sheds light on both immediate and long-term evolutionary trends within SvA and SvB strains from The Gambia.…”

Genomic insights into local scale evolution of ocularChlamydia trachomatisstrains within and between individuals in Gambian trachoma-endemic villages

“…Sample collection was explained in detail by Barton et al . [29]. Briefly, for the initial screening, nine villages were chosen based on information from the Gambian National Eye Care Program (NECP), which conducted a trachoma rapid assessment survey in the Western and North Bank Regions, identifying villages where active trachoma was approximately 20% in school-age children.…”

“…We generated genetic data from 11 SvA and 30 SvB variants collected from four villages in two administrative regions on opposing sides of the river Gambia to elucidate (i) the factors driving the diversification of ocular Ct strains; (ii) disparities in mutation frequency and accumulation profiles; (iii) selective pressures between SvA and SvB; and (iv) the dynamics of mutation accumulation within the Gambian ocular Ct positive population over a short timeframe. This study was done in the context of an investigation of Ct infection-induced immune responses and protection in trachoma [29,30], with Ct molecular diagnosis and ompAsequencing the priority for the extracted DNA [31][32][33]. Nevertheless, an opportunistic selection of samples from this prospective cohort study allowed us to analyze Ct genomes from individuals that repeatedly tested positive over the study period, and sheds light on both immediate and long-term evolutionary trends within SvA and SvB strains from The Gambia.…”