The immune response to malaria sporozoite antigens in animal models and humans: a retrospective overview and present goals

RESUMO

Research and ultimate goals of our sdutides in mamaria immunity is reviewed. A new experimental vector for Plasmodium gallinaceum, an avian malaria, the mosquito Aedes fluviatilis is described. Sporozoites recovered from oocyst (OoS), before they enter salivary glands, are infective for chickens although somewhat less so than the mature salivary gland sporozoites (SGS). The repetitive portion of the circumsporozoite (CS) membrane protein is not responsible for migration/maturation of the OoS into the salivary glands or for infectivity for the vertebrate although present in both populations. The older sporozoites, recovered from mosquitos 4-5 weeks after infection, gradually lose infectivity for chickens. An age-dependent response of chickens to a sporozoite-induced malaria is described, young animals being more susceptible. Monoclonal antibodies (MoAb) have been produced against surface antigens of P. gallinaceum sporozoites, epecific for OoS and SGS antigens, as judged by indirect immunofluorescence and circumsporozoite precipitation tests. By Western blot or by competitive ELISA, these MoAbs recognize the repeat epitope of the CS protein, two polypeptides of molecular weight 64 an 76 kDa, as do the sera from mice immunized with sporozoites. Tested against live sporozoites, these MoAb showed variable protective activity, some of them totally inhibiting parasite infectivity in in vivo and in vitro tests. Cross-reactivity occurred between these MoAb and sporozoites of Plasmodium berghei as well as with their CS protein repeats but no cross-protection was demonstrated against this rodent malaria. Our studies in human malaria in the Amazon area are restricted to the last two years, and to a small sample (180) of individuals recently exposed to transmission of Plasmodium falciparum and P. vivax. A variable but low number (9-30 percent) had anti-CS antibodies and a positive cellular immune response (30-40 percent) in vitro to recombinant CS proteins (of P. falciparum and P. vivax). We found no correlation between these two parameters; between antigen responsiveness and time of exposure to malaria transmission (up to ten years); or between the number of previous malaria infections. In previous studies we showed that individulas who had been exposed but did not acquire malaria, in a focal area of transmission in Minas Gerais, had antisporozoite antibodies...