Cellular responses to Loa loa experimental infection in mandrills (Mandrillus sphinx) vaccinated with irradiated infective larvae

Abstract

In order to shed light on the mechanisms of antifilarial protective immunity, we investigated the course of experimental loaiosis after vaccination in a nonhuman primate host, Mandrillus sphinx. Six vaccinated (V) mandrills received 50 irradiated L3 while six nonvaccinated (NV) received saline solution on days -60, -30 and -15. All animals were challenged with 100 intact L3 (day 0). Parasitological and immunological status were followed for 9 months. Vaccination delayed the appearance and mean peak of microfilaraemia. Five mandrills (Mf-) were never microfilaraemic (one V mandrill) or microfilaraemic on only one occasion (2 V and 2 NV), the other seven having stable microfilaraemia (Mf+). The cytokine response of peripheral blood mononuclear cells to L3 (L3 Ag) was Th2 dominated, while microfilariae (Mf Ag) elicited a Th0-like response. During vaccination, Th2 cytokine production significantly increased in V mandrills against L3 Ag, as well as Mf Ag, whereas Th1 cytokines decreased. On day 60 postinoculation, cellular proliferation was higher in V mandrills in response to L3 and Mf Ags and PHA-L mitogen. At the end of prepatency (on day 130), mandrills with delayed appearance of microfilaraemia exhibited a high, transient IL-2 and IL-4 secretion in response to L3 Ag. Finally, high anti-Mf Th2 cytokine levels characterized Mf-mandrills not only during prepatency, but also (for IL-5) before immunization. However, the presence of a balanced Th1 anti-L3 response during prepatency in the amicrofilaraemic mandrill suggests its importance in protective immunity. Taken together, our data suggest that Th2 cells and also Th1 components of the antifilarial response, especially to larval antigen, may contribute to parasite elimination.

In a bovine model of onchocerciasis, protective immunity exists naturally, is absent in drug-cured hosts, and is induced by vaccination

“…Anti-Mf immunity against the bovine parasite Onchocerca lienalis has been successfully induced in mice by homologous immunization by using live L 3 (45), presumably as a result of antigenic crossreactivity between these life-cycle stages. Furthermore, inoculation of mandrills with irradiated L 3 of Loa loa resulted in the delayed onset of microfilaraemia after challenge (28). However, it is also possible that immune-mediated damage directed against challenge larvae in the current study resulted in impaired fecundity of the adult ''breakthrough'' infections, as has been reported in the L. sigmodontis model (46), and this is certainly consistent with the reduced numbers of gravid females recovered from vaccinated animals.…”

“…Thus, O. volvulus (25), Brugia pahangi (26), and Litomosoides sigmodontis (27) have been used in murine (surrogate) hosts. Natural host-filaria systems in which significant protection has been demonstrated include Loa loa in mandrills (28), Acanthocheilonema viteae in jirds (29), and Dirofilaria immitis (30) in dogs. However, in this report, the irradiated L 3 vaccine is shown to reduce the burden of a filarial infection under conditions of intensive field challenge and in a natural Onchocerca sp.…”

Resistance to reinfection in rats induced by irradiated metacercariae of Clonorchis sinensis

“…Attempts to induce protection induced by γ-irradiated infective stages were performed in some parasites, Fasciola hepatica, S. mansoni, S. japonicum, Loa loa, Brugia malayi, Achantocheilonema viteae, B. pahangi (Creaney et al 1995, Zhang et al 1999, Ungeheuer et al 2000. In these studies, that the infective larvae when optimally attenuated cannot develop into adults will die in the host, which induce high level of protection was proved.…”

A Comprehensive, Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

“…Vaccine studies in this model have been limited to vaccination with irradiated L3 larvae. Three different trials have been performed, in which mandrills were vaccinated with 50 to 150 L3s irradiated with 40 to 45 kilorads (221,222,227). These studies showed a delay in peak microfilaremia in the vaccinated mandrills but no significant decrease in microfilaremia.…”