The invention provides immunogen polypeptides comprising fragments of VAR2CSA protein expressed by P. falciparum as potential second-generation placental malaria vaccine candidates. VAR2CSA is the leading antigen target for a placental malaria vaccine, where associated antibody titers are correlated with protection. Aspects of the inventive immunogen polypeptides comprise all or portions of the chondroitin sulfate A (CSA) binding regions of VAR2CSA, as identified by a structural study of VAR2CSA conducted by the inventors, that possess great sequence conservation among P. falciparum strains when compared to competing clinical vaccine candidates PRIMVAC and PAMVAC. Also provided are methods of using the immunogen polypeptides for vaccination and treatment of disease.
The VAR2CSA immunogens bind to oncofetal CSA, a putative therapeutic target for multiple cancers, including NSCLC, breast, bladder and 40-50% of all pediatric solid tumors. Oncofetal CSA is only expressed solely in the placenta, except in several cancerous tissues, making it an ideal target for targeted therapeutics such as immunogens that are cross linked to cytotoxic agents.
- Placental malaria vaccine
- CSA-binding proteins for cancer therapeutics
- Strain-transcending immunogens for vaccination
- Improved immunogen production through expression of key protein regions