A parallel session on Wednesday, chaired by Dr Pauline Beattie (EDCTP Association) and Professor Halidou Tinto (Institut de Recherche en Sciences de la Santé (IRSS) ,Burkina Faso), featured talks on both RTS,S/AS01 and R21/Matrix-M as well as new vaccines in development.
New vaccines
Dr Aina-ekisha Kahatano (Ifakara Health Institute, Tanzania) described the results of a phase Ib trial of a novel two-dose vaccine, SUM-101, based on the merozoite surface protein MSP1, which targets both red blood cell and liver stages of infection. The antigen is being delivered alongside the GLA-SE adjuvant (although alternative adjuvants are being sourced due to the lack of availability of GLA-SE).
A phase Ia study in Germany showed that the vaccine was safe and immunogenic. The phase Ib study in malaria-exposed adults in Tanzania identified no safety concerns and showed that the vaccine stimulated good antibody production and promising responses in functional assays. The data support an extension of studies to younger age groups.
Dr Adama Sacko (Malaria Research and Training Center (MRTC), Mali) discussed the use of a controlled human infection model in Mali to assess the efficacy of a novel multistage malaria vaccine, ProC6C-AlOH/Matrix-M, designed to prevent both infection and transmission.
In this trial, TBVax3, 34 adult volunteers at a site near Bamako were infected with sporozoites after vaccination to examine both efficacy against infection (prevention of parasitaemia) and effects on transmission, determined by use of a mosquito feeding assay. The vaccine showed excellent efficacy at preventing infection. However, this success made it difficult to assess effects on transmission due to the reduction in gametocyte production.
R21/Matrix-M
R21/Matrix-M has been recommended for use in children 5–17 months old in areas of moderate and high transmission. Dr Angela Gwakisa (Ifakara Health Institute, Tanzania) presented some of the results from the phase III trial of R21/Matrix-M in two areas of Tanzania with differing intensities of malaria transmission.
The trial identified no safety issues. Efficacy against clinical malaria was high at seasonal and standard sites. Notably, efficacy after four doses of the vaccine appeared to differ by age, with protection apparently higher in younger children. Targeting younger children might therefore deliver greater health gains.
Dr Edgard Dabira (MRC Unit The Gambia at The London School of Hygiene and Tropical Medicine, The Gambia) described results from the R21/Matrix-M study, a multi-centre cluster randomised trial in The Gambia and Burkina Faso, which has been evaluating the impact of mass seasonal vaccination across all ages with R21/Matrix-M.
This study also found no safety concerns. Baseline prevalence was found to be significantly higher in Burkina Faso and good vaccine coverage was achieved in both countries. Vaccination reduced both the incidence and prevalence of malaria but vaccine efficacy was higher in The Gambia. Notably, in Burkina Faso but not The Gambia, greater efficacy was seen in the youngest age group (<5 years old).
RTS,S/AS01
The pivotal phase III study of RTS,S/AS01 identified some potential safety signals, which led WHO to recommend a pilot implementation study. Embedded in this pilot programme, organised in Ghana, Kenya and Malawi, was a study that used a case control approach to examine vaccine efficacy and key safety signals. Dr Thomas Gyan (Ghana Health Service) discussed some of the key findings to emerge from this study.
The study focused on conditions identified as possible issues in the phase III trial – meningitis, severe malaria and a ‘rebound’ effect in children who receive only three doses of vaccine. The case-control approach is based on comparing each case with closely matched controls, which can reveal whether RTS,S/AS01 vaccination is associated with the outcome of interest.
The study found that vaccination was not associated with a higher risk of meningitis but was associated with a substantially decreased risk of cerebral malaria. There were no indications of a long-term increased risk of malaria in children receiving just three doses. The findings confirm the good safety of RTS,S/AS01.
Despite the positive results from these studies, participants emphasised the importance of combining vaccination with other approaches to malaria control, including use of insecticide-impregnated bed nets.