Mal067- Understanding RTS,S malaria vaccine-induced protection through integrated analysis of antibody, B cell and T cell immune responses

Mal067- Understanding RTS,S malaria vaccine-induced protection through integrated analysis of antibody, B cell and T cell immune responses

Objectives

1. To define the initial protective immune responses targeting CSP upon vaccination with RTS,S/AS01E.

2. To explain duration of protection by defining RTS,S/AS01E modulation of naturally acquired humoral and cellular immunity to asexual blood stage parasites

 

PI Institution(s)

Principal Investigator (PI)

Funding source(s)

Partner(s)

Abstract

A Phase 3 trial of the RTS,S/AS01E malaria vaccine is underway in multiple African trial sites. A first interim analysis has shown a vaccine efficacy of 55.8% (95% CI 50.6-60.4) against clinical malaria and 47.3% (95% CI 22.4-64.2) against severe malaria. Previous trials have shown that in some circumstances the duration of protection afforded by the vaccine was at least 45 months while in others it waned at 3 months. Initial results of the phase 3 interim analysis have maintained opened questions regarding the duration of vaccine- induced protection, which may be affected by differing malaria transmission intensities among trial sites. The aim is 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 3 trial. RTS,S delivered in combination with the AS adjuvant system was designed to elicit strong antibody, TH1 and cytotoxic responses to the circumsporozoite protein (CSP). However, understanding of the mechanisms of protection is only partial. Based on clinical and immunogenicity data from Phase 2 studies, a model of how protection is developed has been proposed. The study hypothesis is that long term immunity against clinical malaria depends on two distinct, but related, mechanisms: 1) initial partial pre-erythrocytic protection via induction of vaccine-specific humoral and cellular immune responses, and 2) long term immunity resulting from enhancement of blood stage immunity facilitated through partial RTS,S protection. Vaccine efficacy may also be affected by parasite-driven immune modulation such as hyporesponsive populations of memory B cells. Identification of immune correlates of protection will also accelerate the evaluation of second generation vaccines against malaria.

Mal067

Key facts

  • Dates
    Jun 2012 to Jul 2017
    Funding amount
    $3,159,764
    Country
    • Gabon
    • Kenya
    • Tanzania, United Republic of
    • Mozambique
    • Burkina Faso
    • Ghana

MESA tags

  • Methodology
    Basic science
    Theme(s)
    Immune correlates of protection