Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria

Gregory Mullen, Ruth D. Ellis, Kazutoyo Miura, Elissa Malkin, Caroline Nolan, Mhorag Hay, Michael P. Fay, Allan Saul, Daming Zhu, Kelly Rausch, Samuel Moretz, Hong Zhou, Carole A. Long, Louis H. Miller, John Treanor

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

Background: Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.

Methods: A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 mu g of AMA1-C1/Alhydrogel (R)+564 mu g CPG 7909 (n = 15), 80 mu g of AMA1-C1/Alhydrogel (R) (n = 30), or 80 mu g of AMA1-C1/Alhydrogel+564 mu g CPG 7909 (n = 30).

Results: Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG) were detected by enzyme-linked immunosorbent assay (ELISA), and the immune sera of volunteers that received 20 mu g or 80 mu g of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 mg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.

Conclusion/Significance: The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.

Trial Registration: ClinicalTrials.gov NCT00344539

Original languageEnglish
Article numbere2940
Number of pages13
JournalPL o S One
Volume3
Issue number8
DOIs
Publication statusPublished - 13 Aug 2008

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