CD4(+) T cells acting independently of antibody contribute to protective immunity to Plasmodium chabaudi infection after apical membrane antigen 1 immunization

Apical membrane Ag 1 (AMA1) is a leading malaria vaccine candidate. Homolog ues of AMA1 can induce protection in mice and monkeys, but the mechanism of immunity is not understood. rc;lice immunized with a refolded, recombinant , Plasmodium chabaudi AMA1 fragment (AMA1B) can withstand subsequent challe nge with P, chabaudi adami. Here we show that CD4(+) T cell depletion, but not gamma delta T cell depletion, can cause a significant drop in antiparas ite immunity in either immunized normal or immunized B cell KO mice. In nor mal mice, this loss of immunity is not accompanied by a decline in Ab level s. These observations indicate a role for AMA1-specific Ab-independent T ce ll-mediated immunity. However, the loss of immunity in normal CD4(+) T cell -depleted mice is temporary. Furthermore, immunized B cell KO mice cannot s urvive infection, demonstrating the absolute importance of B cells, and pre sumably Ab, in AMA1-induced immunity, CD4(+) T cells specific for a cryptic conserved epitope on AMA1 can adoptively transfer protection to athymic (n u/nu) mice, the level of which is enhanced by cotransfer of rabbit anti-AMA 1-specific antisera, Recipients of rabbit antisera alone do not survive. So me protected recipients of T cells plus antisera do not develop their own A MA 1-specific Ab response, suggesting that AMA 1-specific CMI alone can pro tect mice. These data are the first to demonstrate the specificity of any p rotective CMI response in malaria and have important implications for devel oping a malaria vaccine.