There is considerable evidence that MSA-1 is the target of a protective immune response. Two groups have reported that human monoclonal antibodies against P. falciparum MSA-1 inhibit growth of the parasite in vitro (Brown, 1986; Schmidt-Ullrich et al., 1986). Passive transfer experiments using anti-MSA-1 monoclonal antibodies have demonstrated protection against P. yoelii and P. chabaudi infection in mice (Boyle et al., 1982; Majarian et al., 1984; Burns et al., 1989). These monoclonal antibodies recognize epitopes in the carboxy-terminal half of MSA-1, the portion of the antigen that carries over into the trophozoite stage of the parasite (Burns et al., 1989; Lew et al., 1989).
Active immunization studies with purified MSA-1 have shown protection against P. yoelii in mice (Holder and Freeman, 1981), P. knowlesi in saimiri monkeys (Schmidt-Ullrich et al., 1983), and P. falciparum in saimiri and aotus monkeys (Hall et al., 1984; Cheung et al., 1985; Siddiqui et al., 1987). Immunization with synthetic peptide fragments of MSA-1 has demonstrated some efficacy in saimiri and aotus monkeys (Cheung et al., 1986; Patarroyo et al., 1987). Finally, MSA-1 has been used as part of a combination-peptide antigen in the human trial reported by Patarroyo et al. (1988). Of some concern, however, is the report that mice immunized with MSA-1 and challenged with a different P. chabaudi strain were unprotected (Brown et al., 1985). The full meaning of such results can be determined only after the structure of MSA-1 in different parasite strains is known.
Since immunization with MSA-1 provides at least partial protection against malaria, it is likely that immunogens derived from MSA-1 will be included in a successful multivalent malaria vaccine. Efforts to express MSA-1 by recombinant DNA techniques have so far failed, due in part to the difficulty in obtaining the correct conformational structure of the protein. Recent research using baculovirus vectors may have solved this problem (Murphy et al., 1990), and it is likely that recombinant MSA-1 fragments will soon be tested in humans.
A vaccine that induces an immune response to the sexual stages of the malaria parasite will not necessarily protect against infection with sporozoite or blood-stage parasites. It may, however, have a dramatic effect on reducing malaria transmission by slowing or halting human-to-mosquito (and thus mosquito-to-human) spread of infectious parasites. A transmission-blocking vaccine can be considered “altruistic, ” as it benefits primarily the uninfected or nonimmune individuals in a community, providing little or no benefit to those actually immunized. (Carter et al., 1988; Kaslow, 1990; Targett et al., 1990).