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

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...

The immunodominant surface antigen of Plasmodium gallinaceum is present in both the salivary gland and oocyst sporozoites

1. Monoclonal antibodies (MAbs) against surface antigens of Plasmodium gallinaceum sporozoites, an avian malaria parasite, were produced using spleen cells from mice immunized with sporozoites from mosquito salivary glands (SGS) or from midadgusts containing oocysts (OoS). 2. All of the 15 MAbs teted (11 anti-SGS and 4 anti-OoS) reacted with SGS and OoS by indirect immunofluorescence and circumsporozoiter precipitation reactions. Fourteen of these MAbs (11 anti-SGS and 3 anti-OoS) produced a Western blot (WB) patten identical to that produced with serum from mice lyperimmunized with viable intacts sporozoites. 3. All MAbs and the immune sera recognized only two polypeptide bands of approximate molecutlar weight 78 and 64KDa. 4. No difference in the WB pattern was observed when-or 12-day SGS or OoS extracts were used as antigens in WB. This antigenic similary was confirmed when the total protein extracts were visualized on silver-stained SDS-PAGE gel