This study examined the development and persistence of immunity in humans presenting defined states of Onchocerca volvulus
infection, i.e. in exposed endemic control individuals without microfilaridermia and clinical disease, in patients with patent or post-patent
onchocerciasis, and in patients concurrently infected with Mansonella perstans. Onchocerca volvulus
antigen (OvAg)-specific cellular reactivity was significantly diminished in microfilariae (mf)-positive patients, while the highest reactivity was measured in exposed but mf-negative endemic controls, those being free of any clinical signs of onchocercal disease. In patients who became post-patent, responses to OvAg were significantly augmented, but did not approach entirely the magnitude observed in endemic controls. In
onchocerciasis patients with concurrent
mansonelliasis, cellular unresponsiveness to OvAg persisted, even when mf of O.
volvulus were eliminated permanently by repeated
ivermectin therapy. Cells from mf-positive
onchocerciasis patients produced significantly less
interferon-gamma (IFN-gamma) (P < 0.01) and
interleukin-5 (IL-5) (P < 0.05) in response to OvAg than those taken from endemic controls or post-patent individuals in whom IFN-gamma and
IL-5 production was similarly high. In contrast, both OvAg-driven as well as spontaneous
IL-10 secretion was higher in mf-positive patients than in endemic controls or post-patent cases. In all individuals examined, serological recognition of OvAg by
immunoglobulins was dominated by
IgG4; in mf-positive patients OvAg of 205,000-12,000 molecular weight (MW) were strongly bound. In post-patent individuals, and similarly in endemic controls. OvAg recognition by
IgG4 varied from intense (with numerous
antigens being recognized) to weak or absent
antigen binding. Significantly elevated OvAg-specific
IgG isotypes were measured in mf-positive
onchocerciasis patients in comparison with endemic controls or post-patent individuals (with the exception of
IgG3).
IgG1,
IgG2 and
IgE were higher, but
IgG4 was lower in endemic controls compared with post-patent
onchocerciasis patients. The ratios of
IgG4/
IgG1 differed (P < 0.001) between endemic controls and mf-positive or post-patent
onchocerciasis patients, with
IgG4/
IgG1 ratios of R < 3.0 being characteristic for endemic controls and post-patent O.
volvulus infection. In conclusion, this cross-sectional immunoepidemiological investigation showed that distinct states of O.
volvulus infection correlate with a particular cellular and humoral immune response. The mf-free condition appeared to be associated with a vigorous parasite-specific cellular reactivity and a particular
cytokine production profile, while concurrent M. perstans
infection depressed OvAg-specific cellular responsiveness. Antibody responses, in all likelihood, reflected the intensity and state of
infection, and not the degree of acquired immunity protective against parasite aggregation.