Last Updated: 02/12/2024
Study of immune correlates of protection against malaria after vaccination with RTS,S/AS01E. A comprehensive immunological arm of a phase III double-blind, randomized, controlled multi-centre trial (MAL055-Immuno)
Objectives
This project, MAL055-Immuno or MAL067 study, is a multicenter immunology ancillary study nested within MAL055, that aims to address key gaps in the knowledge of RTS,S mode of action through the analysis of well-characterized plasma and peripheral blood mononuclear cell samples collected in the pediatric phase III trial (MAL055).
In this study is proposed to conduct a single multi-centre co-operative study which presents the required expertise, rigour and power to investigate the immunological basis of RTS,S-induced immunity. The proposal is to go beyond the current measurement of the vaccine-induced antibody response, that of acquired anti-circumsporozoite protein antibody titres, and to include assessment of the isotype (subclasses), quality (affinity/avidity) and functionality (invasion/development inhibition/sporozoite migration) of the IgG antibody responses against pre-erythrocytic antigens. In addition, the aim is to measure cellular immune responses (B and T cells) induced after vaccination with RTS,S/AS01E in a subset of study children at the screening and at cross-sectional visits. Finally, it is proposed to measure the induction of antibody and cellular immune responses against the blood stage of Plasmodium falciparum to further investigate potential mechanisms of RTS,S-induced long-term protection.
The specific objectives of the study are:
- To describe induction of antibody and cellular immune responses against pre erythrocytic and asexual erythrocytic stage P. falciparum antigens after vaccination with RTS,S/AS01E.
- To compare antibody and cellular immune responses induced by RTS,S/AS01E between age cohorts (infants 6-12 weeks of age vs. children 5-17 months of age).
- To assess the effect on antibody and cellular immune responses of a fourth “booster” dose of RTS,S/AS01E vaccine.
- To compare antibody and cellular immune responses induced by RTS,S/AS01E between geographical areas of different malaria transmission intensities.
- To describe immune correlates associated with vaccine and naturally acquired protection.
Manhiça Health Research Centre (CISM), Mozambique
Swiss Tropical and Public Health Institute (Swiss TPH), Switzerland
Ifakara Health Institute (IHI), Tanzania
London School of Hygiene and Tropical Medicine (LSHTM), United Kingdom
Joint Malaria Programme (JMP), Tanzania
Medical Research Center Lambarene (CERMEL), Gabon
Noguchi Memorial Institute for Medical Research (NMIMR), Ghana
Research Institute of Health Sciences (IRSS), Burkina Faso
KEMRI Wellcome Trust Research Programme, Kenya
GlaxoSmithKline (GSK), United Kingdom
Identifying correlates of protection to accelerate vaccine trials: systems evaluation of two models of experimentally-induced immunity to malaria (SysMalVac)
Pilot phase for the MAL067 RTS,S immunology ancillary study
Understanding RTS,S malaria vaccine-induced protection through integrated analysis of antibody, B cell and T cell immune responses
A study of the alteration of B cell functionality associated with malaria and its impact on susceptibility to co-infections and vaccination
As the defining study for RTS,S vaccine formulated in the AS01E adjuvant (RTS,S/ASO1E) licensure, and probably the last trial in which there would be an unvaccinated control group, the phase III trial MAL055 offers the best opportunity to understand the mechanisms of vaccine action and immune correlates of vaccine-induced protection.
The ancillary immunology study is being conducted in 8 of the 11 clinical trial sites participating in the RTS,S/AS01E Phase III vaccine trial and includes two age cohorts (infants 6-12 weeks of age and children 5-17 months of age).
Jan 2009 — Dec 2013
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