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Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

Appendix A
Vaccine Trials

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
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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

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

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

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

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

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

 

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

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

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

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

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

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

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

Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
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Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
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Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
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Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

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Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

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Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×

Stoute JA, Kester KE, Krzych U, Wellde BT, Hall T, White K, Glenn G, Ockenhouse CF, Garcon N, Schwenk R, Lanar DE, Sun P, Momin P, Wirtz RA, Golenda C, Slaoui M, Wortmann G, Holland C, Dowler M, Cohen J, Ballou WR. 1998. Long-term efficacy and immune responses following immunization with the RTS,S malaria vaccine. Journal of Infectious Diseases 178(4):1139–1144.

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Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 81
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 82
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 83
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 84
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 85
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 86
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 87
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 88
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 89
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 90
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 91
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 92
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 93
Suggested Citation:"Appendix A Vaccine Trials." Institute of Medicine. 2006. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program. Washington, DC: The National Academies Press. doi: 10.17226/11656.
×
Page 94
Next: Appendix B Current Requirements for a Malaria Vaccine »
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Malaria is an infectious disease common to several parts of the world, including Africa, northern South America, and Asia. During their service in the military, U.S. active members may be sent to any part of the world, including parts of the world where Malaria is an issue. In Liberia in 2003, for example, there was a 28 percent attack rate in Marines who spent a short time ashore, and half of the 80 Marines affected needed to be evacuated to Germany. This was not only costly to the U.S. military but dangerous as well. To fight against this disease, there exists a Malaria Vaccine program in the U.S. military. However, there exists a variety of potential vaccine targets for the most severe and important form of malaria; malaria from the species Plasmodium falciparum. Issues also arise with the fact that there are three possible stages to create vaccines against—preerythrocytic, blood, or transmission.

The Department of Defense (DoD), through the commanding general of the U.S. Army Medical Research and Materiel Command (USAMRMC), requested that the Institute of Medicine (IOM) conduct a programmatic review of the military Plasmodium falciparum malaria vaccine research and development program. There was to be a focus on vaccine against the preerythrocytic and blood stages. The IOM formed a committee of 11 experts with collective expertise in malaria vaccine research, parasite immunology, malarial biology, clinical trials and regulatory affairs, industrial and public-sector vaccine development, biologic products research and development (vaccinology), military research and development programs, tropical medicine, and public health.

The committee focused different tasks including determining whether the DoD malaria vaccine research and development program is scientifically sound and able to achieve the vaccine program objectives within specified timelines, recommending how to overcome significant, identified barriers, and identifying major strategic goals and timelines based on the material received and presentations made by the DoD's program representatives. Battling Malaria: Strengthening the U.S. Military Malaria Vaccine Program presents the committee's findings, current malaria vaccines, and recommendations for the development of the U.S. Military vaccine research.

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