Immunization with hybrid hepatitis B virus core particles carrying circumsporozoite antigen epitopes protects mice against Plasmodium yoelii challenge

The hepatitis B virus nucleocapsid antigen (HBcAg) was investigated as a carrier moiety for circumsporozoite protein (CS) repeat B cell epitopes of the rodent malaria agent Plasmodium yoelii. A vector expressing a hybrid gene coding for the dominant CS repeat epitope (QGPGAP)4 was constructed and transformed into avirulent Salmonella typhimurium. The resulting hybrid HBcAg-CS polyproteins were purified from recombinant Salmonella typhimurium. They purified as particles and displayed HBc as well as P. yoelii CS antigenicity. To investigate immunogenicity and protective efficacy, BALB/c mice were immunized with the hybrid HBcAg-CS particles. Immunization resulted in high titered antinative CS serum IgG antibody litres. BALB/c mice immunized with hybrid HBcAgCS particles were between 90-100% protected against subsequent P. yoelli challenge. Protective immunity persisted for a minimum of three months. These data confirm the previous suggestion (Schödel et al., 1994), that hybrid HBcAg particles could become a useful component of future human malaria vaccines.