The anti-sporozoite
P. falciparum vaccine RTS, S is now under extensive testing in clinical trials in sub-Saharan Africa. Phase II controlled trials of the vaccine in Gambian men [
9] and Mozambiquan children [
10,
11] demonstrated protective efficacy of 30 – 45% against
P. falciparum parasitaemia, but differed in one remarkable respect. Vaccine-elicited parasitological benefit was transient in Gambian men, having diminished within 16 weeks of vaccination, whereas RTS, S-vaccinated children in Mozambique enjoyed a reduction in malaria episodes through 18 months of follow-up [
11]. A parsimonious explanation for this discrepancy in the observed duration of protection afforded by RTS, S is that vaccinated children gained enhanced anti-parasite immunity, compared to controls, that the men already enjoyed irrespective of vaccination status. As RTS, S appears to offer protection to only a proportion of those vaccinated, it is also likely that incomplete protection in some vaccinated individuals impairs release of post-liver-stage merozoites without completely preventing it [
12]. This may lead to attenuated blood-stage parasite infections, and support the development of blood-stage immunity [
2]. Thus, by partially and transiently preventing maturation of liver-stage parasites, RTS, S may be eliciting effective anti-blood-stage immunity in a proportion of vaccinated children, but not in adults.
The development of protective blood-stage immunity by this proposed mecanism would be dependent on: