The observation that a vaccine that reduces exposure to the parasite is associated with an increase in IgG1 or IgG3 levels to certain antigens, and that this increase may be associated with malaria protection, could be related to the fact that RTS,S does not result in sterile immunity, particularly during the course of primary vaccination; instead, it is a partially-effective or “leaky” PE vaccine. This evidence concerns the gene IGHG3 and malaria.