Anti-malarial antibodies in twins

Abstract

A central tenet of the strategy underlying malaria subunit vaccine development in recent years has been the need to include immunodominant B-cell and Tcell epitopes of a number of antigens of Plasmodium fdciparum. It is reasoned that not only will this promote the immunogenicity of such a multivalent vaccine but that it will also provide for anamnestic responses through memory T cells and for long-lasting antibodydndependent cellular immunity after boosting by natural infection. An antigen that has been much studied as a vaccine candidate against P. falciparum is the merozoitederived polypeptide Pf155 or ringinfected erythrocyte surface antigen (RESA) 1,2. There are several reasons for selecting Pf155/RESA for vaccine development. Although antigenic polymorphism is very common among malaria parasites, Pf155/RESA is unusual in that it is well conserved in different isolates of P. falciparum 3. Also, a high proportion of clinically immune individuals from malariaendemic areas have high levels of antibodies to Pf155/RESA in their sera 4, while antibodies to this antigen block merozoite invasion of erythrocytes, in vitro s. However, from a critical perspective, after invasion of erythrocytes by merozoites, Pf155/RESA becomes associated with the cytoskeleton beneath the red blood cell membrane. Given the location of the molecule, it is uncertain how a protective antibody to Pf155/ RESA is effective. Recent work has involved the characterization of immune responses to defined epitopes of Pf155/RESA. Within the molecule, there is conspicuous and extensive repetition of a number of amino acid sequences, typical of malarial antigens. A major proportion of human merozoite invasionblocking antibodies is directed against linear epitopes made up from these sequences. By using short synthetic peptides corresponding to these epitopes, the group from Stockholm University, headed by Peter Perlmann, has been able to dissect B-cell and T-cell responses in individual malaria-immune donors (for review, see Ref. 6). They have shown that, although within highly endemic areas such as Liberia, approxi-