Immunological mechanisms underlying protection mediated by RTS,S: a review of the available data

Abstract

The RTS,S/AS candidate malaria vaccine has demonstrated efficacy against a variety of endpoints in Phase IIa and Phase IIb trials over more than a decade. A multi-country phase III trial of RTS,S/AS01 is now underway with submission as early as 2012, if vaccine safety and efficacy are confirmed. The immunologic basis for how the vaccine protects against both infection and disease remains uncertain. It is, therefore, timely to review the information currently available about the vaccine with regard to how it impacts the human-Plasmodium falciparum host-pathogen relationship. In this article, what is known about mechanisms involved in partial protection against malaria induced by RTS,S is reviewed.

Figure 1

The relationship between a protective immune response and reduction in risk of a defined malaria endpoint. If the risk of a defined malaria endpoint (infection or disease) is inversely related to a vaccine-induced immune response, it may be possible to describe this relationship graphically. Three hypothetical relationships are shown above. The blue dashed line represents a relationship for which a clear threshold could be calculated using efficacy trial data, but in a biological system such a relationship is perhaps less likely than the dotted green and solid red lines.