An autologous falciparum vaccine using the erythrocyte’s band 3 molecule

Summary 

Protection against the serious complications of falciparum malaria is provided to people with the minor forms of hematological conditions such as sickle cell disease and thalassemia and as a result natural selection has increased their incidence in malaria endemic areas. The explanation for this has thus far not been determined but experimental evidence that is now available suggest an explanation that also has therapeutic implications.

The hypothesis presented suggests that the erythrocytes of these blood disorders experience premature senescence and are then eliminated by the same process that normally disposes of senescent erythrocytes. Erythrocytes express approximately one million widely dispersed band 3 molecules on their surface but when these erythrocytes age they form band 3 clusters that are recognized by the immune system which results in their elimination. In addition to senescent erythrocytes, both sickle and falciparum infected erythrocytes also display these clusters suggesting that band 3 antibodies contribute to their erythrocytes removal. Supporting band 3’s involvement in falciparum erythrocyte elimination are the facts that band 3 specific antibodies are elevated in falciparum endemic areas and the documentation that the falciparum erythrocytes displaying these clusters are rapidly phagocytized.

Both sickle and falciparum infected erythrocytes adhere to endothelium and band 3 antibodies and adhesive band 3 peptides block this adhesion. This proves that the band 3 molecule is responsible for at least some of the endothelial adhesion and implies that band 3 antibodies are active in eliminating falciparum infected erythrocytes. It is proposed that the band 3 peptides could be used to develop a vaccine to reduce the lethality of falciparum infections. A conjugate vaccine using these peptides in early infancy may allow those infants to survive a falciparum infection and develop comprehensive natural immunity to the local endemic parasite.