Immunity to Malaria and Naturally Acquired Antibodies to the Circumsporozoite Protein of Plasmodium falciparum

A candidate Plasmodium falciparum sporozoite vaccine, R32tet 32 , which includes 32 tetrapeptide repeats derived from the circumsporozoite protein of P. falciparum , has been developed on the basis of the hypothesis that antibodies to the repeat region of this protein will protect against sporozoite infection. The results of two in vitro assays, the circumsporozoite precipitation reaction and the inhibition of sporozoite invasion into hepatoma cells, are thought to indicate protective immunity. We therefore tested serum samples from persons living in a hyperendemic malarious area of Indonesia for antibodies against R32tet 32 and for their ability to produce circumsporozoite precipitation and to inhibit sporozoite invasion of hepatoma cells. The prevalence and mean titer of antibody against R32tet 32 increased with the age of the subjects, whereas the prevalence of P. falciparum infection in the community decreased. Only serum samples with IgG or IgM R32tet 32 antibody titers ≥1/800 had precipitation activity and invasion-inhibiting activity of more than 75 percent. When the serum samples were fractionated by affinity chromatography, only the fractions containing purified human antibody to R32tet 32 were found to contain this activity. These data support the hypotheses that antibodies to the circumsporozoite protein are important in reducing the prevalence of malaria with increasing age among persons in areas in which malaria is endemic and that vaccine-elicited antibody to the circumsporozoite repeat region will protect against infection with P. falciparum sporozoites. (N Engl J Med 1986; 315: 601–6.) There is now little hope that malaria, which affects 100 to 300 million persons and may cause 1 million deaths per year, 1 can be adequately controlled without vaccines. Malaria is transmitted to humans by inoculation of sporozoites through the bites of anopheline mosquitoes. The membranes of infective sporozoites are covered by a polypeptide called the circumsporozoite protein. 2 The gene for the circumsporozoite protein of Plasmodium falciparum encodes a protein of 412 amino acids, 40 percent of which are included in 41 tandem repeated tetrapeptides: 37 of these are Asn-Ala-Asn-Pro and 4 are Asn-Val-Asp-Pro. 3 All monoclonal antibodies raised against sporozoites recognize . . .