A phase 1, randomized, controlled dose-escalation study of EP-1300 polyepitope DNA vaccine against Plasmodium falciparum malaria administered via electroporation

Abstract

Plasmodium falciparum malaria is one of the leading infectious causes of childhood mortality in Africa. EP-1300 is a polyepitope plasmid DNA vaccine expressing 38 cytotoxic T cell epitopes and 16 helper T cell epitopes derived from P. falciparum antigens expressed predominantly in the liver phase of the parasite's life cycle. We performed a phase 1 randomized, placebo-controlled, dose escalation clinical trial of the EP-1300 DNA vaccine administered via electroporation using the TriGrid Delivery System device (Ichor Medical Systems). Although the delivery of the EP-1300 DNA vaccine via electroporation was safe, tolerability was less than that usually observed with standard needle and syringe intramuscular administration. This was primarily due to acute local discomfort at the administration site during electroporation. Despite the use of electroporation, the vaccine was poorly immunogenic. The reasons for the poor immunogenicity of this polyepitope DNA vaccine remain uncertain.

Clinical trials registration: ClinicalTrials.gov NCT01169077.

Keywords: Electroporation; Malaria; Phase 1; Plasmodium falciparum; Polyepitope DNA vaccine; Vaccine.

Copyright © 2016 Elsevier Ltd. All rights reserved.

Figures

Fig. 1

Schematic Depiction of EP-1300 DNA Vaccine Plasmid. Epitopes are shown separated by spacer peptides, with HLA restriction indicated below each epitope. The vaccine insert was cloned into the backbone plasmid pMB75.6. The functional elements of the expression plasmid are also indicated. Note that each epitope included in the vaccine plasmid is detailed in Supplemental Tables 1 and 2 for ease of reference.

Fig. 2

CONSORT diagram for the EP-1300 trial.

Fig. 3

A) IFN-γ ELISPOT Responses by HLA peptide pool. Peptides were pooled by HLA restriction and evaluated in triplicate wells. Shown are the median responses for participants by dosage group vs. placebo, after correcting for background levels. Dashed black line indicates placebo recipients, and day is shown on the x-axis. ALL represents median responses for all HLA supertypes combined. B) IFN-γ ELISPOT Responses, all peptide pools. Shown are results of ELISPOT from 3 time points by dosage group vs. placebo. Box plots indicate median and 25th (lower box line) and 75th (upper box line) percentiles, with whiskers indicating 5th and 95th percentiles.

Fig. 4

Anti-CSP ELISA Responses. Geometric means of the optical density (OD) for participants in the 1.0 mg and 4.0 mg groups compared to placebo are shown.