Table 3: Malaria vaccine candidates clinically tested classified as a function of the adjuvant.

AdjuvantAntigenLife cycle stageClinical stage

AlumSPf66Multistage Short-term antibodies, low cellular response. Nonreproducible reduction of incidence (28%) [22]. Candidate discontinued, antigen reformulated
PfCS102PreerythrocyticLow and nonfunctional antibodies [23]. Candidate discontinued, antigen reformulated
ICC-1132PreerythrocyticLow and non-functional antibodies [79]. Candidate discontinued, antigen reformulated
RTS,SPreerythrocyticNo efficacy on challenge trials [81]. Candidate discontinued, antigen reformulated
MSP1-C142Blood stageModerate antibody levels, poor cellular response. No efficacy field trials [24]. Candidate discontinued, antigen reformulated
Blood stageModerate antibody levels, poor cellular response. No efficacy field trials [25]. Discontinued candidate, antigen reformulated
AMA1-C1Blood stageModerate antibody levels, poor cellular response. No efficacy field trials [26]. Candidate discontinued, antigen reformulated
Multistage Moderate antibody levels, poor cellular response. No efficacy field trials [27]. Candidate discontinued, antigen reformulated
EBA-175 RIIBlood stageFunctional antibodies, parasite growth inhibition, and parasite binding [28]
Blood stageHumoral response [29]
Blood stageHumoral response, parasite recognition. IFN-γ and lymphoproliferation [30]. Progressed to Phase II
GMZ2Multistage Cytophilic antibodies, cross-reactivity, cell memory for 1 year [31]. Progressed to Phase II
SE36Blood stageAntibody response [32]
Pf25Sexual stagePoor immunogenicity, reactogenicity [59]. Reformulated by conjugation to P. Aeruginosa EPA recombinant protein [35]
Pv25Sexual stagePoor immunogenicity [59]

AS04RTS,SPreerythrocyticNo protection in challenge trials [81]

AS03RTS,SPreerythrocyticStrong antibody level. Moderate efficacy (25%) in challenge trials [48]

QS21SPf66Multistage Higher and longer-lasting antibody levels than Alum. Allergy [66]. Antigen discontinued

Montanide ISA-720PfCS102PreerythrocyticSpecific and functional antibodies, short-term cellular response [23]. No efficacy in challenge trials [52]
ICC-1132PreerythrocyticStrong antibody response, low T cell response. No efficacy in challenge trials [80]
Combination BBlood stageLow antibody response, strong T cell response in field trials. No parasite inhibition in challenge trial [54, 55]
PfCP2.9Blood stageHigh but no functional antibodies [56]
Blood stageStrong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults [25]
AMA1-C1Blood stageStrong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults. Antigen instability reported [57].
Multistage Strong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults [27]
Blood stageStrong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults [29]
MSP2-C1Blood stageStrong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults. Unacceptable reactogenicity [58]
Pf25Sexual stageModerate antibody levels. Severe reactogenicity and erythema nodosum [59]
Pv25Sexual stageLow antibody levels. Reactogenicity [59]

AS02PfCS102PreerythrocyticHigher humoral and cell-mediated response than ISA-720 [98]
FMP011PreerythrocyticStrong antibody and CD4+ T cell response. No efficacy in challenge trials [99]
RTS,SPreerythrocyticPartial protection in challenge and in adult field trials (32%) [100]. Partial protection against clinical and severe malaria (30 and 39%) in children after 45 month followup [103]. Partial protection against clinical malaria (33%) in infants after 14-month followup [2]
Blood stageHigher antibody levels and parasite inhibition than ISA-720 [25]
FMP1Blood stageImmunogenicity. No efficacy in challenge trials [105]
FMP2.1Blood stageStrong humoral and cellular responses, naïve adults and field children. Reduction of parasitemia. No protection in field trials [106, 107]

AS01FMP011PreerythrocyticImmunogenicity. No efficacy in challenge trials [99]
RTS,SPreerythrocyticModerate protection in naïve adults (50%) [100]. Efficacy of 55% in children 5–17 months and 30% in infants 4–16 weeks after a followup of 1 year [3, 113]
FMP2.1Blood stageNo protection, no parasitemia reduction [106]

Alum + CPG7909AMA1-C1Blood stageHigher specific and functional antibodies and parasite inhibition than Alum alone [103]. Memory B cell only in nonexposed individuals [119]
MSP1-C142Blood stageHigher specific and functional antibodies and parasite inhibition than Alum alone [24]. Memory B cell only in nonexposed individuals [119]
BASM-2Blood stagePreliminary stage, parasite growth inhibition [120]

VirosomesPEV302PreerythrocyticSafety, immunogenicity after boosting [128]
PEV301Blood stageSafety, immunogenicity after boosting. Inhibition of sporozoite migration and hepatocyte invasion [127]
PEV3AMultistage Immunogenicity related to PEV301 and PEV302, additionally to parasite growth inhibition [129, 130]. No protection in challenge model [131]

Viral vectorsF9/MVA CSPPreerythrocyticNo efficient induction of effector T cells in naïve volunteers but moderate in endemic population. No protection [136, 138]
DNA/MVA CSPPreerythrocyticNo efficient induction of effector T cells. No protection [137]
FP9/MVA ME-TRAPPreerythrocyticStrong CD4+ IFN- γ secretion in healthy volunteers [139]. No protection in field trials [140]
DNA/MVA ME-TRAPPreerythrocyticStrong CD8+ IFN-γ secretion in healthy volunteers [139]. Low protection against infection (10%) in field trials [141]
F9/MVA polyproteinMultistageT-cell responses. No protection after challenge [142]
NMRC-M3V-Ad-PfCMultistageSafety, specific immunogenicity prevented after boosting. No protection after challenge [143]
Ad35.CS/RTS,S-AS01PreerythrocyticNot published human protection data
Ad35.CS/Ad26.CSPreerythrocyticNot published human protection data
ChAD63/MVA ME-TRAPPreerythrocyticCD4/CD8 mixed effector response [147]. Certain protection level in 57% of individuals after challenge [148]
ChAD63/MVA MSP1Blood stageCD4/CD8 mixed effector response, no effect on parasite growth after challenge [151, 153]
ChAD63/MVA AMA1Blood stageCD4/CD8 mixed effector response, no effect on parasite growth after challenge [152, 153]

VLPs adjuvants, ICC-1132, and RTS,S are considered within delivery adjuvants with which they were coadministered (Alum, Montanide ISA-720, adjuvant systems (AS)).