Antibody response inPlasmodium vinckei malaria after treatment with chloroquine and adjuvant interferon-?

Abstract

The antibody response of mice infected with Plasmodium vinckei after treatment with chloroquine either alone or in combination with interferon-gamma (IFN-gamma) was determined. Sequential serum samples were drawn from BALB/c mice receiving either 240 micrograms chloroquine on the day of infection or 120 micrograms chloroquine plus 10(4) units IFN-gamma daily for 11 days beginning on day 3 prior to infection. Mice treated with additional IFN-gamma showed an early induction of IgG2a response and a reduction in IgG1 antibodies as detected by the immunofluorescence technique at between 10 and 16 days after infection as compared with mice treated with chloroquine alone. Thus, IFN-gamma may partly exert its antimalarial activity via the induction of IgG2a antibody formation. At 4-6 weeks after infection, when mice from both groups resisted homologous re-infection, the predominant antibody isotypes found in both groups were IgG1 and IgG2a. Serum samples obtained from mice in both treatment groups at 6 weeks after infection were used for serum transfer experiments. When parasitised erythrocytes were preincubated with such immune serum, a retardation of the course of parasitaemia by 2 days was observed.

Reciprocal Regulation of Th1- and Th2-Cytokine-Producing T Cells during Clearance of Parasitemia inPlasmodium falciparumMalaria

“…Taking both Th1 and Th2 data together, a more pronounced Th2-driven response (a lower ratio of IFN-␥ expression to IL-4 expression) during acute untreated P. falciparum malaria was replaced by a shift towards a Th1-biased response (a higher ratio of IFN-␥ expression to IL-4 expression) paralleling the clearance of parasitemia in peripheral-blood T cells. High IFN-␥ production as part of a Th1-driven immune response has been associated with a more favorable outcome in most animal models of malaria (13,14,20,21,23,25), and treatment of the otherwiselethal murine Plasmodium vinckei infection with IFN-␥ greatly enhanced the effect of antimalarial chemotherapy (8,16,21). This effect has been attributed to the monocyte/macrophageactivating capacities of IFN-␥, with rapid killing of the malarial blood-stage parasites by reactive oxygen and nitrogen intermediates (1,27).…”

Cytokines as adjuvants for vaccines: antigen-specific responses differ from polyclonal responses

“…Here, the efficacy of IL-2 as an adjuvant can be further improved if the cytokine is encapsulated into liposomes. It has also been shown that IFN-␥ increases the therapeutic effects of chloroquine in malaria (14); here, the survival rate is correlated with increased levels of IgG2a antibodies. In a recent study, it was shown that IL-12 has an adjuvant effect in a vaccine against Leishmania major (1).…”

“…Although most of the issues raised in this review have been targeted towards antigen-specific responses, this effort should not neglect the significance of persistent polyclonal stimulation (14,16,41). Indeed, there are a number of viral, bacterial, and parasitic diseases in which a major concern is dealing with the undesirable effects of polyclonal stimulation.…”

Cellular mechanisms in the immune response to malaria in Plasmodium vinckei-infected mice

“…However, these results do not imply that antibodies and/or B cells may not also have a role in the clearance of P. vinckei infection, as they have roles in other rodent malaria models, such as P. yoelii or P. berghei (35,53,54). Thus, P. vinckei-infected mice treated with curative doses of chloroquine in combination with IFN-␥ develop immunity characterized by an early induction of IgG2a antibodies and accompanied by a reduction of IgG1 antibodies (13). The transfer of antibody-treated E i suggests that these humoral immune responses may well contribute to solid anti-P. vinckei immunity.…”