Fc-receptors and immunity to malaria: from models to vaccines.

The complexity and number of antigens (Ags) seen during an immune response has hampered the development of malaria vaccines. Antibodies (Abs) play an important role in immunity to malaria and their passive administration is effective at controlling the disease. Abs represent approximately 25% of all proteins undergoing clinical trials, and these 'smart biologicals' have undergone a major revival with the realization that Abs lie at the interface between innate and adaptive immunity. At least 18 Abs have FDA approval for clinical use and approximately 150 are in clinical trials, the majority for the treatment of cancer, allograft rejection or autoimmune disease. Despite these triumphs none are in development for malaria, principally because they are perceived as being too expensive for a disease mainly afflicting poor and marginalized populations. Although unlikely, at least in the foreseeable future, that Ab-based prophylaxis will be made available to the millions of people at risk from malaria, they may be incorporated into current vaccine approaches, since Abs act as correlates of protection in studies aimed at defining the best Ags to include in vaccines. Abs may also form the basis for novel vaccination strategies by targeting Ags to appropriate antigen presenting cells. Therefore, to develop the most efficacious vaccines it will be necessary to fully understand which Abs and Fc-receptors (FcRs) are best engaged for a positive outcome.