Author
Listed:
- 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
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 µg of AMA1-C1/Alhydrogel®+564 µg CPG 7909 (n = 15), 80 µg of AMA1-C1/Alhydrogel® (n = 30), or 80 µg of AMA1-C1/Alhydrogel+564 µg 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 µg or 80 µg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 µg 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
Suggested Citation
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 & , 2008.
"Phase 1 Trial of AMA1-C1/Alhydrogel plus CPG 7909: An Asexual Blood-Stage Vaccine for Plasmodium falciparum Malaria,"
PLOS ONE, Public Library of Science, vol. 3(8), pages 1-13, August.
Handle:
RePEc:plo:pone00:0002940
DOI: 10.1371/journal.pone.0002940
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0002940. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.