Human immune recognition of polymorphic malaria proteins

Dr. J. McBride

Understanding of how parasites are controlled by the immune system is a major question in the development of malaria vaccines. Immunity to endemic P.falciparum malaria is acquired only after exposure to repeated infections but reasons for this slow response are not known. Since genes encoding many proteins of the parasite are polymorphic in natural populations, a hypothesis favours the notion that immunity to this malaria is parasite 'strain'-specific. Merozoite surface proteins which are among candidates for a malaria vaccine are highly polymorphic but the significance of their genetic polymorphism for functional antigenic diversity, specificity of human immune responses or implications for prospects of a vaccine is not well understood. To assess whether such proteins could be a target of 'strain'-specific immunity, it needs to be determined whether their polymorphic regions stimulate specific immune responses in humans. The problem is approached by comparisons between antigenic profiles of infecting parasites and the specificity of antibodies induced by them in individual hosts. Primary sequences of selected polymorphic domains are determined, correlated with antigenic profiles of the parasites, and recombinant antigens representing the predominant antigenic variants are used to determine specificity of immune responses mounted by the same patients.

References

Conway D J, Cavanagh D R, Tanabe K, Roper C, Mikes Z S, Sakihama N, Bojang K A, Oduola A M J, Kremsner P G, Arnot D E, Greenwood B M and McBride J S (2000) A principal target of human immunity to malaria identified by molecular population genetic and immunological analyses. Nature Medicine, 6: 689-692

Cavanagh D R, I M Elhassan, C S Roper, V J Robinson, H Giha, A A Holder, L Hviid, T G Theander, D E Arnot and J S McBride (1998) A longitudinal study of type-specific antibody responses to Plasmodium falciparum merozoite surface protein 1 in an area of unstable malaria in Sudan. Journal of Immunology 161: 347-359.