BioMed Research International

Review Article

Malaria Vaccine Adjuvants: Latest Update and Challenges in Preclinical and Clinical Research

Table 3

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


Adjuvant	Antigen	Life cycle stage	Clinical stage

Alum	SPf66	Multistage	Short-term antibodies, low cellular response. Nonreproducible reduction of incidence (28%) [22]. Candidate discontinued, antigen reformulated
	PfCS102	Preerythrocytic	Low and nonfunctional antibodies [23]. Candidate discontinued, antigen reformulated
	ICC-1132	Preerythrocytic	Low and non-functional antibodies [79]. Candidate discontinued, antigen reformulated
	RTS,S	Preerythrocytic	No efficacy on challenge trials [81]. Candidate discontinued, antigen reformulated
	MSP1-C1₄₂	Blood stage	Moderate antibody levels, poor cellular response. No efficacy field trials [24]. Candidate discontinued, antigen reformulated
		Blood stage	Moderate antibody levels, poor cellular response. No efficacy field trials [25]. Discontinued candidate, antigen reformulated
	AMA1-C1	Blood stage	Moderate 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 RII	Blood stage	Functional antibodies, parasite growth inhibition, and parasite binding [28]
		Blood stage	Humoral response [29]
		Blood stage	Humoral response, parasite recognition. IFN-γ and lymphoproliferation [30]. Progressed to Phase II
	GMZ2	Multistage	Cytophilic antibodies, cross-reactivity, cell memory for 1 year [31]. Progressed to Phase II
	SE36	Blood stage	Antibody response [32]
	Pf25	Sexual stage	Poor immunogenicity, reactogenicity [59]. Reformulated by conjugation to P. Aeruginosa EPA recombinant protein [35]
	Pv25	Sexual stage	Poor immunogenicity [59]

AS04	RTS,S	Preerythrocytic	No protection in challenge trials [81]

AS03	RTS,S	Preerythrocytic	Strong antibody level. Moderate efficacy (25%) in challenge trials [48]

QS21	SPf66	Multistage	Higher and longer-lasting antibody levels than Alum. Allergy [66]. Antigen discontinued

Montanide ISA-720	PfCS102	Preerythrocytic	Specific and functional antibodies, short-term cellular response [23]. No efficacy in challenge trials [52]
	ICC-1132	Preerythrocytic	Strong antibody response, low T cell response. No efficacy in challenge trials [80]
	Combination B	Blood stage	Low antibody response, strong T cell response in field trials. No parasite inhibition in challenge trial [54, 55]
	PfCP2.9	Blood stage	High but no functional antibodies [56]
		Blood stage	Strong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults [25]
	AMA1-C1	Blood stage	Strong 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 stage	Strong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults [29]
	MSP2-C1	Blood stage	Strong antibody response, PBMC proliferation, IFN-γ, parasite inhibition in malaria-naïve adults. Unacceptable reactogenicity [58]
	Pf25	Sexual stage	Moderate antibody levels. Severe reactogenicity and erythema nodosum [59]
	Pv25	Sexual stage	Low antibody levels. Reactogenicity [59]

AS02	PfCS102	Preerythrocytic	Higher humoral and cell-mediated response than ISA-720 [98]
	FMP011	Preerythrocytic	Strong antibody and CD4+ T cell response. No efficacy in challenge trials [99]
	RTS,S	Preerythrocytic	Partial 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 stage	Higher antibody levels and parasite inhibition than ISA-720 [25]
	FMP1	Blood stage	Immunogenicity. No efficacy in challenge trials [105]
	FMP2.1	Blood stage	Strong humoral and cellular responses, naïve adults and field children. Reduction of parasitemia. No protection in field trials [106, 107]

AS01	FMP011	Preerythrocytic	Immunogenicity. No efficacy in challenge trials [99]
	RTS,S	Preerythrocytic	Moderate 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]
	FMP2.1	Blood stage	No protection, no parasitemia reduction [106]

Alum + CPG7909	AMA1-C1	Blood stage	Higher specific and functional antibodies and parasite inhibition than Alum alone [103]. Memory B cell only in nonexposed individuals [119]
	MSP1-C1₄₂	Blood stage	Higher specific and functional antibodies and parasite inhibition than Alum alone [24]. Memory B cell only in nonexposed individuals [119]
	BASM-2	Blood stage	Preliminary stage, parasite growth inhibition [120]

Virosomes	PEV302	Preerythrocytic	Safety, immunogenicity after boosting [128]
	PEV301	Blood stage	Safety, immunogenicity after boosting. Inhibition of sporozoite migration and hepatocyte invasion [127]
	PEV3A	Multistage	Immunogenicity related to PEV301 and PEV302, additionally to parasite growth inhibition [129, 130]. No protection in challenge model [131]

Viral vectors	F9/MVA CSP	Preerythrocytic	No efficient induction of effector T cells in naïve volunteers but moderate in endemic population. No protection [136, 138]
	DNA/MVA CSP	Preerythrocytic	No efficient induction of effector T cells. No protection [137]
	FP9/MVA ME-TRAP	Preerythrocytic	Strong CD4+ IFN- γ secretion in healthy volunteers [139]. No protection in field trials [140]
	DNA/MVA ME-TRAP	Preerythrocytic	Strong CD8+ IFN-γ secretion in healthy volunteers [139]. Low protection against infection (10%) in field trials [141]
	F9/MVA polyprotein	Multistage	T-cell responses. No protection after challenge [142]
	NMRC-M3V-Ad-PfC	Multistage	Safety, specific immunogenicity prevented after boosting. No protection after challenge [143]
	Ad35.CS/RTS,S-AS01	Preerythrocytic	Not published human protection data
	Ad35.CS/Ad26.CS	Preerythrocytic	Not published human protection data
	ChAD63/MVA ME-TRAP	Preerythrocytic	CD4/CD8 mixed effector response [147]. Certain protection level in 57% of individuals after challenge [148]
	ChAD63/MVA MSP1	Blood stage	CD4/CD8 mixed effector response, no effect on parasite growth after challenge [151, 153]
	ChAD63/MVA AMA1	Blood stage	CD4/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)).