Malaria Vaccine: AMA1-C1

Duffy, Patrick

Abstract

In collaboration with Oxford University, a small Phase 2a challenge study was conducted where volunteers were immunized with AMA1-C1/Alhydrogel+CPG 7909, followed by a challenge dose of erythrocytes infected with malaria parasites. A significant correlation was observed between parasite multiplication rate and both vaccine-induced growth-inhibitory activity and AMA1 antibody titers. However, this did not translate to an overall observable clinically relevant vaccine effect in these volunteers. Currently the collaboration with Oxford University continues in a prime-boost study where volunteers are primed with viral-vectored AMA1 vaccines followed by a booster dose of AMA1-C1/Alhydrogel+CPG 7909. The AMA1-C1/Aldhyrgel+CPG7909 is also being tested in combination with another merozoite stage antigen in an Aotus challenge model.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAI001001-06
• Application #: 8555927
• Support Year: 6
• Fiscal Year: 2012
• Total Cost: $403,341

Institution

• Name: National Institute of Allergy and Infectious Diseases

Publications

Duncan, Christopher J A; Hill, Adrian V S; Ellis, Ruth D (2012) Can growth inhibition assays (GIA) predict blood-stage malaria vaccine efficacy? Hum Vaccin Immunother 8:706-14

Zhu, Daming; Huang, Shuhui; McClellan, Holly et al. (2012) Efficient extraction of vaccines formulated in aluminum hydroxide gel by including surfactants in the extraction buffer. Vaccine 30:189-94

Miura, Kazutoyo; Perera, Suwani; Brockley, Sarah et al. (2011) Non-apical membrane antigen 1 (AMA1) IgGs from Malian children interfere with functional activity of AMA1 IgGs as judged by growth inhibition assay. PLoS One 6:e20947

Zhu, Daming; McClellan, Holly; Dai, Weili et al. (2011) Long term stability of a recombinant Plasmodium falciparum AMA1 malaria vaccine adjuvanted with Montanide(®) ISA 720 and stabilized with glycine. Vaccine 29:3640-5

Duncan, Christopher J A; Sheehy, Susanne H; Ewer, Katie J et al. (2011) Impact on malaria parasite multiplication rates in infected volunteers of the protein-in-adjuvant vaccine AMA1-C1/Alhydrogel+CPG 7909. PLoS One 6:e22271

Ellis, Ruth D; Sagara, Issaka; Doumbo, Ogobara et al. (2010) Blood stage vaccines for Plasmodium falciparum: Current status and the way forward. Hum Vaccin 6:

Ouattara, Amed; Mu, Jianbing; Takala-Harrison, Shannon et al. (2010) Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine. Malar J 9:175

Miura, Kazutoyo; Zhou, Hong; Diouf, Ababacar et al. (2009) Anti-apical-membrane-antigen-1 antibody is more effective than anti-42-kilodalton-merozoite-surface-protein-1 antibody in inhibiting plasmodium falciparum growth, as determined by the in vitro growth inhibition assay. Clin Vaccine Immunol 16:963-8

Crompton, Peter D; Mircetic, Marko; Weiss, Greta et al. (2009) The TLR9 ligand CpG promotes the acquisition of Plasmodium falciparum-specific memory B cells in malaria-naive individuals. J Immunol 182:3318-26

Sagara, Issaka; Dicko, Alassane; Ellis, Ruth D et al. (2009) A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali. Vaccine 27:3090-8