A randomized controlled phase 2 trial of the blood stage AMA1-C1/Alhydrogel malaria vaccine in children in Mali

Abstract

A double blind, randomized, controlled Phase 2 clinical trial was conducted to assess the safety, immunogenicity, and biologic impact of the vaccine candidate Apical Membrane Antigen 1-Combination 1 (AMA1-C1), adjuvanted with Alhydrogel ® . Participants were healthy children 2-3 years old living in or near the village of Bancoumana, Mali. A total of 300 children received either the study vaccine or the comparator. No impact of vaccination was seen on the primary endpoint, the frequency of parasitemia measured as episodes >3000 per μL per day at risk. There was a negative impact of vaccination on the hemoglobin level during clinical malaria, and mean incidence of hemoglobin <8.5 g/dL, in the direction of lower hemoglobin in the children who received AMA1-C1, although these differences were not significant after correction for multiple tests. These differences were not seen in the second year of transmission.

Comparing the Understanding of Subjects Receiving a Candidate Malaria Vaccine in the United States and Mali

“…[13][14][15] A Phase 1,2 study was also conducted in 2-3 year old children in Donéguébougou and Bancoumana, Mali, with most of the participants recruited in Bancoumana, the larger village. 16,17 4 Questionnaires for all persons screened for participation were reviewed for this study. At JHU/CIR, age and sex were recorded as part of the baseline demographic information; all volunteers could sign their names and were considered to be literate.…”

Evaluating antidisease immunity to malaria and implications for vaccine design

“…So far, tremendous progress has been made, and several targets have been identified as vaccine candidates. In fact, a vaccine based on a liver stage antigen, the circumsporoite protein (CSP), has made it all the way to licensure (RTS,S vaccine),16, 17, 18, 19 while a handful of other antigens have been characterized and are in phases II and III clinical trials 20, 21, 22, 23, 24…”

Passive Immunoprotection of Plasmodium falciparum-Infected Mice Designates the CyRPA as Candidate Malaria Vaccine Antigen

“…Unfortunately, the most advanced blood-stage vaccine Ags, AMA-1 and MSP-1, have not demonstrated efficacy in African children to date (14,34,35). However, a multistage vaccine comprising an AMA-1 component showed a 50% reduced incidence rate of clinical malaria episodes in child vaccinees compared with that of control children (36).…”