[Source: PLoS One, full page: (LINK). Abstract, edited.]
OPEN ACCESS / PEER-REVIEWED / RESEARCH ARTICLE
Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study
Kwadwo A. Koram , Bright Adu, Josephine Ocran, Yaa S. Karikari, Susan Adu-Amankwah, Michael Ntiri, Benjamin Abuaku, Daniel Dodoo, Ben Gyan, Karl C. Kronmann, Francis Nkrumah
Published: September 19, 2016 / http://dx.doi.org/10.1371/journal.pone.0163066
The erythrocyte binding antigen region II (EBA-175 RII) is a Plasmodium falciparum ligand that mediates erythrocyte invasion and is considered an important malaria vaccine candidate. A phase Ia trial in malaria naïve adults living in the United States found the recombinant non-glycosylated vaccine antigen, EBA-175 RII-NG adjuvanted with aluminium phosphate to be safe, immunogenic and capable of inducing biologically active antibodies that can inhibit parasite growth in vitro. The aim of the current study was to assess the safety and immunogenicity of this vaccine in malaria exposed semi-immune healthy adults living in a malaria endemic country, Ghana. In this double-blinded, placebo controlled, dose escalation phase I trial, eighteen subjects per group received ascending dose concentrations (5 μg, 20 μg or 80 μg) of the vaccine intramuscularly at 0, 1 and 6 months, while 6 subjects received placebo (normal saline). The primary end point was the number of subjects experiencing Grade 3 systemic or local adverse events within 14 days post-vaccination. Serious adverse events were assessed throughout the study period. Blood samples for immunological analyses were collected at days 0, 14, 28, 42, 180 and 194. A total of 52 subjects received three doses of the vaccine in the respective groups. No serious adverse events were reported. The majority of all adverse events reported were mild to moderate in severity, with local pain and tenderness being the most common. All adverse events, irrespective of severity, resolved without any sequelae. Subjects who received any of the EBA-175 RII-NG doses had high immunoglobulin G levels which moderately inhibited P. falciparum growth in vitro, compared to those in the placebo group. In conclusion, the EBA-175 RII-NG vaccine was safe, well tolerated and immunogenic in malaria semi-immune Ghanaian adults. Its further development is recommended.
Trial registration ClinicalTrials.gov. Identifier: NCT01026246
Citation: Koram KA, Adu B, Ocran J, Karikari YS, Adu-Amankwah S, Ntiri M, et al. (2016) Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study. PLoS ONE 11(9): e0163066. doi:10.1371/journal.pone.0163066
Editor: Mohammad Ali, Johns Hopkins Bloomberg School of Public Health, UNITED STATES
Received: May 7, 2016; Accepted: August 29, 2016; Published: September 19, 2016
This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Data Availability: All relevant data are within the paper and its Supporting Information files.
Funding: The study product was developed by Leidos with support from National Institute of Allergy and Infectious Diseases (NIAID) (https://www.niaid.nih.gov) [contract N01-AI-05421 awarded to Leidos]. The study was sponsored by the Division of Microbiology and Infectious Diseases (DMID), NIAID/ US NIH (https://www.niaid.nih.gov) under Contract No. HHSN266200400016C awarded to Noguchi Memorial Institute for Medical Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The product developed in this study is owned by DMID /NIAID. Leidos was a contract manufacturer and has no commercial interests whatsoever after delivering the product to DMID/NIAID. Leidos had no part in the design, conduct, analysis or interpretation of data from the study. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.
Keywords: Research; Abstracts; Malaria; Vaccines.