Protective immunity in vaccinated mice depended on strong T-cell activation, and antibody and cytokines also played an important role in resolving parasitaemia [21, 24-26], indicating that both cell- and antibody-mediated mechanisms selleck are essential for the development of immunity in vaccinated mice. In mice vaccinated against lethal P. yoelii, protective immunity also depended on strong T-cell activation,

and both antibody and cytokines were also shown to play an important role in resolving parasitaemia [21, 24-26]. Varying degrees of protective immunity were reported with attenuated whole sporozoite and blood-stage merozoite vaccines in different mouse–parasite combinations. We found that mice protected against the lethal P. yoelii 17XL parasite were partially protected against Plasmodium berghei

ANKA and showed that immune serum from vaccinated mice that had recovered from lethal P. yoelii 17XL transferred immunity against this parasite to normal recipients [27]. Vaccine-induced protection against lethal P. yoelii 17XL correlated with the induction of specific DTH-type T-cell stimulation and IFN-γ production [25, 28]. Furthermore, we found that while the amount of antibody and its isotypes–IgG1, IgG2a and IgG2b–were important in controlling infection, other host and parasite Rucaparib cell line factors influenced its efficacy [27]. Antibody subclass depended upon the type of adjuvant used [29]. While experimental blood-stage vaccines gave encouraging results in mice, new methods were needed to identify specific parasite antigens for use as potential vaccine candidates in man. The most popular approach was to select antigens that reacted with immune serum. We used isoelectric focussing and reverse-phase HPLC techniques to select a series of antigens to see whether they would induce strong protective immunity in mice. Antigen and delivery system were both critical to the induction of potent T-cell activation

and protection against infection [21, 30]. The best protection was obtained with a crude mixture of soluble parasite antigens and the adjuvant Provax, a formulation originally designed for induction of CD8+ Class 1-restricted T cells [25]. Purified antigens including recombinant medroxyprogesterone MSP1–19 were also protective, although higher concentrations were required for equivalent efficacy. Protection was always associated with the induction of both Th1 and Th2 responses, Th1 responses preceding maximum activation of the Th2 response [24, 25]. This pattern of T-cell responses was also described in mice infected with attenuated nonlethal P. berghei [31] or with Plasmodium vinckei [32], in which Th1 subset activity was crucial for parasite elimination. In the very recent studies from Stefan Kappe’s laboratory, subcutaneous immunization with blood-stage P.