Potent induction of focused Th1-type cellular and humoral immune responsesby RTS,S/SBAS2, a recombinant Plasmodium falciparum malaria vaccine

The RTS,S/SBAS2 vaccine confers sterile protection against Plasmodium falci parum sporozoite challenge. The mechanisms underlying this are of great int erest, yet little is known about the immune effector mechanisms induced by this vaccine. The immune responses induced by RTS,S/SBAS2 were characterize d in 10 malaria-naive volunteers. Several epitopes in the circumsporozoite protein (CSP) were identified as targets of cultured interferon (IFN)-gamma -secreting CD4(+) T cells. RTS,S-specific IFN-gamma-secreting effector T ce lls were induced in 8 subjects; this ex vivo response mapped to a single pe ptide in Th2R. CSP-specific CD8(+) cytotoxic T lymphocytes were not detecte d. RTS,S-specific IFN-gamma production was universal, whereas interleukin-4 and -5 production was rare. RTS,S-specific lymphoproliferative responses a nd antibodies to CSP were strongly induced in all volunteers. Responses wan ed with time but were boostable. Thus, RTS,S/SBAS2 is a potent inducer of T h1-type cellular and humoral immunity. These results highlight possible imm une mechanisms of protection and have important implications for vaccine de sign in general.