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

Abstract

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 registrationClinicalTrials.gov. Identifier: NCT01026246

Targeting malaria parasite invasion of red blood cells as an antimalarial strategy

“…2017), erythrocyte binding antigen (EBA-175, Phase 1a; Koram et al . 2016) and others reaching clinical trials, but with limited efficacy demonstrated to date (reviewed in Draper et al . 2015; Beeson et al .…”

The Search of a Malaria Vaccine: The Time for Modified Immuno-Potentiating Probes

“…Naturally acquired antibodies against EBA-175 have also been shown to inhibit the binding of its invasive ligands to their receptors on RBCs, and these inhibitory antibodies have been associated with a protective immunity [ 136 ]. Adults vaccinated with this antigen showed that it was well tolerated, safe, and immunogenic [ 137 ].…”

Plasmodium falciparum Blood Stage Antimalarial Vaccines: An Analysis of Ongoing Clinical Trials and New Perspectives Related to Synthetic Vaccines

“…An additional randomized, double-blind, phase Ib study evaluated the safety and immunogenicity of EBA-175 RII NG adjuvanted with aluminum phosphate administered in three doses to 60 semi-immune adults in Ghana (Africa) (Koram et al, 2016). Vaccine concentrations (5, 20, and 80 μg) were well tolerated; however, 38 individuals developed grade 1 and grade 2 adverse reactions during follow-up (no severe AE).…”

“…Some limitations found in both trials were related to sample size, short/limited follow-up, and differences between immunological response regarding vaccine concentrations between people exposed to malaria and those not exposed to it. More time must thus be dedicated to developing the EBA-175 RII NG vaccine to improve its Ab functionality due to poor P. falciparum growth inhibition as demonstrated in in vitro trials (Koram et al, 2016).…”