The malaria vaccine--status quo 2013.

It has been 40 years since David Clyde's landmark induction of sterile immunity against deadly falciparum malaria through immunization by exposure to 1000 irradiated mosquitoes, and the first recombinant Plasmodium falciparum vaccine, RTS,S/AS01, is now in Phase III testing. Interim reports from this largest ever Phase III pediatric trial in Africa show the malaria vaccine decreased clinical and severe disease by 56% and 47% respectively in 5-17 month olds, and by 31% and 26% respectively in infants participating in the Expanded Programme on Immunization. Final data in 2014 will more fully describe the efficacy of RTS,S/AS01 over time against all falciparum malaria cases under a variety of transmission conditions, results essential for decisions on licensure and deployment. Meanwhile, candidate components of a second-generation malaria vaccine are emerging. A field trial of the polymorphic blood stage vaccine AMA-1/AS02 demonstrated no overall efficacy (ve = 17%, P = 0.18), yet a sieve analysis revealed allele-specific efficacy (ve = 64%, P = 0.03) against the vaccine strain, suggesting AMA-1 antigens could be part of a multicomponent vaccine. Initial trials of new antigens include the highly conserved pre-erythrocytic candidate PfCelTOS, a synthetic Plasmodium vivax circumsporozoite antigen VMP-001, and sexual stage vaccines containing antigens from both P. falciparum (Pfs25) and P. vivax (Pvs25) intended to interrupt transmission. Targets for a vaccine to protect against placental malaria, the leading remediable cause of low birth weight infants in Africa, have been identified. Lastly, renewed efforts are underway to develop a practical attenuated-sporozoite vaccine to recapture the promise of David Clyde's experiment.