The malaria vaccine RTS,S provides sustained protection against severe malaria 7 years after immunization, according to extended findings from a phase 3 trial published in The Lancet Infectious Diseases.
Initial results of the phase 3 study demonstrated the efficacy of RTS,S (GlaxoSmithKline) against severe and clinical malaria among children over a 3- to 4-year follow-up period, and in July 2015, the vaccine received a “positive regulatory assessment” from the European Medicine Agency, researchers noted. In April of this year, WHO launched a pilot malaria vaccine program using RTS,S in three African countries.
However, a previous phase 2 single-center study demonstrated a decrease in protection over a 7-year period — from 35.9% to 4.4% — among children aged 5 to 17 months who received three doses, researchers noted.
In the current study, researchers investigated malaria incidence up to 7 years following vaccination in an open-label extension study of the initial phase 3 trial, which included infants aged 6 to 12 weeks and children aged 5 to 17 months. They were randomly assigned to receive four vaccine doses (four-dose group), three vaccine doses and a comparator dose (three-dose group) or four comparator doses (control group).
The extension study assessed severe malaria incidences for 3 additional years, from January 2014 to December 2016, after vaccination at three study sites in Tanzania, Kenya and Burkina Faso. The researchers also assessed malaria incidence for up to 6 years among younger children, aged 3 to 5 years (n = 1,345), and up to 7 years among older children, aged 5 to 7 years (n = 1,739).
During the 3-year follow-up, the researchers reported 66 cases of malaria. Among older children in the four-dose group, the incidence of severe malaria was 0.004 cases per person-years at risk (PPY) (95% CI, 0-0.033). In the three-dose group and control group, severe malaria incidence was 0.007 cases PPY (95% CI, 0.001-0.52) and 0.009 cases PPY (95% CI, 0.001-0.066), respectively.
Among younger children in the four-dose group, severe malaria incidence was 0.007 PPY (95% CI, 0.001-0.058). In the three-dose group and control group, severe malaria incidence was 0.007 PPY (95% CI, 0.001-0.054) and 0.011 PPY (95% CI, 0.001-0.083), respectively.
In both age groups, vaccine efficacy against severe malaria did not significantly contribute to the overall efficacy, according to the study.
The researchers noted continued occurrence of malaria transmission. They reported that the incidence of clinical malaria ranged from 0.165 PPY to 3.124 PPY across all study groups and sites. When broken down by group, clinical malaria incidence among older children was 1.079 PPY (95% CI, 0.152-7.662) in the four-dose group, 1.108 PPY (95% CI, 0.156–7.868) in the three-dose group and 1.016 PPY (95% CI, 0.14–7.213) in the control group. The incidence of clinical malaria among younger children was 1.632 PPY (95% CI, 0.23–11.59) in the four-dose group, 1.563 PPY (95% CI, 0.22–11.104) in the three-dose group and 1.686 PPY (95% CI, 0.237–11.974) in the control group.
Overall, the findings showed that incidence of severe malaria was low in all groups and there was no evidence of rebound in recipients of the vaccine.
In a related editorial, Alassane Dicko, MD, PhD, professor at the Malaria Research and Training Center at the University of Bamako in Mali, and Brian Greenwood, CBE, FRCP, FRS, professor of clinical tropical medicine at the London School of Hygiene & Tropical Medicine, noted that among children who received a booster dose of RTS,S, the vaccine was 36.7% effective in older children and 31% effective in younger children during the 6- or 7-year postvaccination period, demonstrating sustained efficacy.
“This study provides strong evidence that RTS,S/AS01 can provide sustained protection against severe malaria and some reassurance on its safety,” they wrote.