Transmission blocking immunity may provide clues that antimalarial immunity is largely T-independent

Abstract

Humans infected with malaria produce antibodies against the sexual stages of the parasite (Mendis et al., 1987; Graves et ai., 1988), as they do against pre-erythrocytic (Nardin et al., 1979) and asexual blood stages (Cohen et al., 1961). These antibodies are evoked by gametocytes which are precursors of the sexual stages that are presented to the host immune system during a blood infection. The antibodies take effect in the midgut of a mosquito when it takes a blood meal from an infected person, where they react either with surface antigens of male and female gametes that are formed in the mosquito midgut and prevent fertilization, or with postfertilization stages such as the zygote, and prevent their further development (reviewed by Carter et ai., 1988). A potent vaccine-induced immunity against these sexual stages could reduce malar'~. ~:ansmission in endemic areas (De Zoysa et ai., i988, i99i). Parasite molecules that are targets of transmissionblocking antibodies have been defined in both of the major human malaria parasites P. falciparum (Carter et al., 1988; Rener et al., 1983; Vermulen et al., 1985) and P. vivax (Premawansa et al., 1990), and the genes coding for two of them, Pfs25, an ookinete antigen of P. falciparum (Kaslow et al., 1988) and GAM-1 of P. vivax (personal communication, P.H. David) have been cloned. The Pfs25 ookinete antigen has been successfully expressed in the vaccinia virus, and immunization of mice with recombinant vaccinia has been . . . . . . s a t ~ , to induce antibodies which blocked the infectivity of P. falciparum gametocytes to mosquitoes in membrane feeding experiments (Kaslow et al., 1991). Thus transmission blocking malaria vaccines may soon be ready for clinical testing.