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Intestinal helminths induce immune suppressive responses thought to regulate inflammatory diseases including allergies and autoimmune diseases. This study was designed to evaluate whether helminthic infections suppress the natural development of systemic lupus erythematosus (SLE) in NZBWF1 mice. Infection of NZBWF1 SLE-prone mice with two nematodes failed to establish long-lasting settlement. However, the Hymenolepis microstoma (Hm) rodent tapeworm successfully established long-term parasitization of NZBWF1 mice and was used to evaluate the suppressive effects of helminth infection. Ten-month-old NZBWF1 mice developed symptoms including autoantibody generation, proteinuria, glomerular histopathology, and splenomegaly, but mice infected with Hm at 2 months of age did not show any clinical signs. Furthermore, infection with Hm reduced lymphocyte activation and increased regulatory T cells in the spleen and mesenteric lymph nodes. These results indicate that infection with Hm protects NZBWF1 mice from naturally developing SLE and suggest that pathological immunity is attenuated, presumably because of the induction of regulatory T cells.

We examined the immunogenicity and the protection by a recombinant blood stage antigen derived from the malaria parasite Plasmodium falciparum SERA (serine-repeat antigen) in squirrel monkeys ( Saimiro sciureus ). The monkeys were immunized with recombinant SE47' protein produced using a synthetic gene expressing amino acids 17-382 (SE47') of the SERA polypeptide in E. coli , with or without Freund's adjuvant. All monkeys administered with SE47' protein developed the antibody. After the challenge by the blood stage P. falciparum (Indochina-1 strain), the mean parasitemia in a group of monkeys immunized with SE47' protein in the absence of the adjuvant was lower than that of the control group, especially in an early phase of the infection. Antibody titers against SERA protein in two of the SE47' monkeys immunized without Freund's adjuvant were stimulated after the parasite challenge. The observed increase in SERA ELISA titers following challenge infection correlated with the degree of protection as assessed by significant reductions in peak levels of parasitemia. In addition, immune serum from SE47' immunized monkeys inhibited the growth of P. falciparum in vitro. These results demonstrate that protective immune responses can be induced by an E. coli -produced recombinant SE47' SERA proteins in Saimiro sciureus monkeys, and further that the humoral immune response after experimental immunization can be boosted by P. falciparum challenge infection, presumably due to native SERA molecules produced by challenge parasites.

We expressed two regions of the serine repeat antigen (SERA) protein of Plasmodium falciparum in Escherichia coli by synthesizing the genes with a changed codon usage. One of the synthetic gene sequences encodes amino acid residues 17-382 (SE47') and the other encodes amino acid residues 586-802 (SE50A). The products produced by the synthetic gene sequences in E. coli accounted for 15-30% of the total bacterial protein. Antisera against both the purified gene products prepared in rats inhibited malaria parasite growth in vitro. The anti-SE47' serum was significantly more inhibitory than the anti-SE50A serum. The described methods provide a large scale preparation of recombinant antigens for improving and producing malaria vaccine.