Experimental onchocerciasis in chimpanzees: cellular responses and antigen recognition after immunization and challenge withOnchocerca volvulusinfective third-stage larvae

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Abstract
Summary: Immunization of chimpanzees with radiation-attenuated infective 3rd-stage larvae (L3) ofOnchocerca volvulusdid not induce strong protective immunity against a subsequent challenge infection; only 1 out of 4 immunized animals remained non-patent (i.e. microfilariae-negative) after challenge, and may have been protected. However, during immunization and before challenge, a broad range of adultO. volvulus-derived antigens (OvAg) and also uterus-derived OvAg were recognized by circulating antibodies; moreover, the repertory of antigens recognized increased further in subsequently patent animals after challenge, particularly in the range ofMr12–42 kDa. In the immunized and non-patent chimpanzee, by contrast, serological recognition of uterus-derived OvAg withMr14 kDa and 105 kDa disappeared by 19 months post-challenge (p.c.). During immunization,Acanthocheilonema viteaeL3 antigens ofMr11–12 kDa were strongly recognized only by the non-patent animal, suggesting that recognition of these antigens may have supported resistance to the subsequent challenge infection. In immunized chimpanzees, a substantial increase in the cellular reactivity to OvAg was induced; this, however, declined by 19 months p.c. to levels similar to those seen prior to immunization. At that time, 3 out of 4 immunized animals were patently infected. The effect of exogenous cytokines onin vitro-reactivity of PBMC to OvAg was examined. Addition of exogenous IL-2 alone, IFN-γ alone, and IFN-γ in combination with IL-2, did not augment net cellular responses to OvAg by PBMC from infected and control chimpanzees. In the presence of IL-4 alone, IL-6 alone, IL-2 with IL-4, IL-2 with IL-4 and IFN-γ, or IL-2 with IL-4 and IL-6, the net cellular reactivity to OvAg increased significantly in patent chimpanzees and reached levels similar to non-patent animals. Thus, non-patent chimpanzees maintain high cellular reactivity to OvAg andin vitrocellular unresponsiveness to OvAg on the part of patent chimpanzees is reversible after addition of several cytokines which act individually or synergistically.