TABLE A-1 Phase 1 Trials of Malaria Vaccines That Did Not (or Have Not Yet) Progressed to Phase 2
Type of Vaccine |
Vaccine Details |
MIDRP Involvement |
Results |
References |
Preerythrocytic Vaccines |
||||
CSP recombinant |
VaxSynCSA: full-length CSP, baculovirus expressed/alum |
No |
Minimally immunogenic (n = 20) |
Herrington et al., 1992 |
|
CVD 908-rCSP: CSP expressed in attenuated Salmonella |
No |
Immunogenic to 3/10 participants |
Gonzalez et al., 1994 |
DNA based |
CSP-DNA |
NMRC |
Good cellular but no antibody responses (n = 20) |
Le et al., 2000; Wang et al., 1998 |
DNA prime/protein boost |
PfCSP DNA/RTS,S AS02A boost |
NMRC |
Antibody, CD4 and CD8 T cells |
Epstein et al., 2004 |
Synthetic peptide |
MAP1NYU: PfCSP-repeats/alum/QS21 |
No |
Good antibody responses |
Nardin et al., 2000 |
|
PfCSP-repeats + T-cell epitopes + Pam3Cys polyoxime |
No |
Good antibody and CD4+ T-cell responses |
Nardin et al., 2001 |
Viruslike particle |
ICC-1132: HBcAg + CSP repeats + T-cell epitopes |
No |
Antibody, CD4+ T cells |
Nardin et al., 2004; Oliveira et al., 2005 |
Erythrocytic Stage Vaccines |
||||
Peptide |
MSP-3/alum or ISA 720 |
No |
Antibody, T cells, interferon |
Audran et al., 2005 |
Recombinant protein |
MSP-1/MSP-2 conjugated to diphtheria toxoid |
No |
Good antibody response; hypersensitivity to diphtheria toxoid |
Ramasamy et al., 1995 |
|
MSP-1/P30P2: two allelic forms of MSP119 plus tetanus toxoid T-cell epitopes |
WRAIR |
Good antibody response in 14/32 |
Keitel et al., 1999 |
|
AMA-1C (3D7 and FVO forms), Pichia pastoris expressed |
No |
Good antibody response to both forms |
Malkin et al., 2005 |
|
AMA-1/ISA 720 |
No |
Low antibody (vaccine instability) |
Saul et al., 2005 |
TABLE A-2 Phase 2 Trials of Malaria Vaccines Using Experimental Challenge of Adult Volunteers from Nonendemic Areas
Type of Vaccine |
Vaccine Details |
MIDRP Involvement |
Results |
References |
Preerythrocytic Vaccines |
||||
Irradiated sporozoites |
Whole parasites |
University of Maryland/NMRC/WRAIR |
95% protection after > 1000 bites |
Clyde, 1975; Herrington et al., 1991; Hoffman et al., 2002; Rieckmann et al., 1979 |
Synthetic peptide |
NANP3-tetanus toxoid |
No |
1/3 protected |
Herrington et al., 1987 |
|
CSP 102 (282-383): CSP C-terminus/alum or ISA 720 |
No |
No protection |
Genton et al., 2005; Lopez et al., 2001 |
CSP recombinant |
R32tet32 (FSV1): CSP repeats/alum |
WRAIR |
1/6 protected |
Ballou et al., 1987 |
|
R32toxA: CSP repeats/Pseudomonas toxin A |
WRAIR |
1/3 protected |
Fries et al., 1992 |
|
R32NS1-81: CSP repeats + 81aa flu A nonstructural protein in MPL/squalene/mycobacterial cell wall |
NMRC/WRAIR |
2/11 protected |
Hoffman et al., 1994 |
|
Repeatless form: CSP N- and C-terminus/liposomes/MPL/alum |
WRAIR |
0/15 protected |
Heppner et al., 1996 |
Viruslike particle |
RTS,S: HBsAg/CSP repeat and C-terminus + adjuvant: 1. alum vs alum/MPL 2. MPL vs oil-in water vs oil-in water/MPL/QS21 3. oil-in-water/MPL/QS21 (AS02) |
WRAIR |
|
|
|
1. 0/6 and 2/8 protected 2. 1/8, 2/7, and 6/7 protected 3. 18/41 protected |
Gordon et al., 1995 Stoute et al., 1997, 1998 Kester et al., 2001 |
||
ICC-1132/I SA 720 HBcAg + CSP repeats and T-epitopes |
Oxford/Apovia (WRAIR provided sporozoites) |
No protection (0/11) following single immunization |
Walther et al., 2005 |
|
Erythrocytic Stage Vaccines |
||||
Recombinant protein |
MSP-1,2/RESA (combination B) with montanide ISA720 (blood-stage challenge) |
No |
0/12 protected |
Lawrence et al., 2000 |
Multistage Vaccines |
||||
Peptide/recombinant |
CSP NANP19/5.1(Exp-1) |
No |
0/13 protected |
Sturchler et al., 1992 |
Recombinant protein |
CSP/MSP-2 (combination A)/alum |
No |
0/33 protected |
Sturchler et al., 1995 |
Type of Vaccine |
Vaccine Details |
MIDRP Involvement |
Results |
References |
DNA plasmids |
MuStDO5: CSP, SSP-2/TRAP, LSA-1, LSA-3, Exp-1 |
NMRC |
0/31 protected |
Wang et al., 2005 |
Recombinant virus |
NYVAC-7: CSP, SSP-2/TRAP, LSA-1, MSP-1, SERA, AMA-1 |
WRAIR |
1/35 protected |
Ockenhouse et al., 1998 |
Heterologous prime-boost |
RTS,S AS02A/CSP MVA or CSP MVA/RTS,S AS02A |
Oxford/WRAIR |
No increase in vaccine efficacy compared to RTS,S |
Dunachie et al., 2006 |
|
RTS,S AS02A/SSP-2/TRAP |
WRAIR |
Decreased vaccine efficacy compared to RTS,S |
Walsh et al., 2004; Heppner, 2006 |
|
RTS,S AS02A/MSP-142 |
WRAIR |
No increase in vaccine efficacy compared to RTS,S |
Heppner et al., 2005; Heppner, 2006 |
|
ME-TRAP DNA/MVA and ME-TRAP fowlpox/MVA |
No |
20% protection |
Bejon et al., 2005; Keating et al., 2005; Webster et al., 2005 |
TABLE A-3 Summarized Results of Randomized Phase 2 Human Malaria Vaccine Trials Using Natural Challenge Conducted to Date (December 2005)
Vaccine Type |
Vaccine Details |
MIDRP Involvement |
Trials and Results |
References |
Preerythrocytic Vaccines |
||||
Synthetic peptide |
CSP (NANP)3-TT |
No |
One trial Burkina Faso, no effect |
Guiguemdé et al., 1990 |
Recombinant protein |
CSP R32toxA |
WRAIR/AFRIMS |
Two trials (Thailand, Kenya), no effect |
Brown et al., 1994; Sherwood et al., 1996 |
Viruslike particle |
RTS,S |
WRAIR |
One trial with adults in the Gambia: weak protection against clinical malaria in first year, boosted in second year to 63%. Two trials in children in Mozambique: weak protection against infection, 26% against clinical malaria, 56% against severe malaria. (see Figure 3-3) |
Alonso et al., 2004, 2005; Bojang et al., 2001 |
Heterologous prime-boost |
ME-TRAP DNA/MVA |
No |
One trial in adults (the Gambia), no effect |
Moorthy et al., 2004 |
Vaccine Type |
Vaccine Details |
MIDRP Involvement |
Trials and Results |
References |
Erythrocytic Stage Vaccines |
||||
Recombinant protein |
MSP-1/MSP-2/RESA (combination B) |
No |
One trial in Papua New Guinea children: reduction in parasite density 49%; reduction in incidence of infections of MSP-2/3D7 (as in vaccine). No effect on clinical malaria |
Genton et al., 2002 |
Multistage Vaccines |
||||
Peptide/recombinant |
CSP NANP19/5.1(Exp-1) |
No |
No cases in either trial group |
Reber-Liske et al., 1995 |
Synthetic peptide |
SPf66 |
Limited WRAIR participation in three trials |
10 trials: little effect in Africa (4 trials) or Asia (1 trial), weak effect in S America (5 trials) |
Acosta et al., 1999; Alonso et al., 1994; Amador et al., 1992; Bojang et al., 1997, 1998; D’Alessandro et al., 1995; Leach et al., 1995; Masinde et al., 1998; Nosten et al., 1996; Noya et al., 1994; Sempertegui et al., 1994; Urdaneta et al., 1998; Valero et al., 1993, 1996 |
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