Attenuated parasites and the development of an erythrocytic-stage vaccine

Abstract

Asexual-stage vaccine candidates may be identified by recognition of antibodies to them in the sera of naturally immune individuals. Once identified, recombinant molecules expressing the relevant antigen can be produced, although such recombinant molecules only seem to be effective at inducing immunity if mixed with adjuvant. More information is needed about the role of antibodies in immunity to malaria. In an animal model, that of Plasmodium berghei in mice, a fairly effective immune response can be produced by inoculating mice with live, proliferating parasites and then keeping the infections subclinical, by drug treatment, for 5 weeks. However, the resultant ‘immune1 individuals carry small numbers of parasites despite the presence of antibody (premunition). Repeated challenge infections are limited by the hosts’ immune responses but sterile immunity is not observed, The immunity that is established only fades in the absence of the parasite, In contrast, inoculation with preparations of disrupted parasites, which do not seem to contain all the antigenic information of the living parasites, do not lead to an immune response which limits parasitaemias. These observations may be the result of antigenic variation. Immunity induced in mice by live, attenuated parasites (but not by extracts) protects against challenge with virulent parasites. Immunity against the attenuated but not the virulent parasite can be transferred by inoculating naive mice with spleen cells from the immunized mice. The mice given spleen cells can then be protected against the virulent parasite by challenge with proliferating, attenuated parasites (but not with extracts). Immune B cells from the immune donor and non-immune CD4 cells in the naive recipient are essential for transfer of immunity.