Phase 1 Trial of AMA1-C1/Alhydrogel plus CPG 7909: An Asexual Blood-Stage Vaccine for Plasmodium falciparum Malaria

• DOI: 10.1371/journal.pone.0002940
• Publication Date: 2008-08-12T21:10:50Z
• Authors: Gregory E. D. 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
• Keywords: CpG site; Merozoite surface protein

Apical Membrane Antigen 1 (AMA1), a polymorphic merozoite surface protein, is leading blood-stage malaria vaccine candidate. This the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with novel adjuvant CPG 7909.A phase trial was conducted at University Rochester 75 malaria-naive volunteers to assess safety and immunogenicity AMA1-C1/Alhydrogel+CPG 7909 vaccine. Participants were sequentially enrolled randomized within dose escalating cohorts receive three vaccinations on days 0, 28 56 either 20 microg AMA1-C1/Alhydrogel+564 (n = 15), 80 AMA1-C1/Alhydrogel 30), or 30).Local systemic adverse events significantly more likely be higher severity addition 7909. Anti-AMA1 immunoglobulin G (IgG) detected by enzyme-linked immunosorbent assay (ELISA), immune sera that received had up 14 fold significant increases anti-AMA1 antibody concentration compared alone. The also elicited AMA1 specific IgG dramatically increased vitro growth inhibition homologous parasites levels as high 96% inhibition.The profile acceptable, given increase observed. Further clinical development ongoing.ClinicalTrials.gov NCT00344539.