Abstract
Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection.
Highlights
About 3.4 billion people, nearly half of the world’s population, live in areas at risk of Plasmodium transmission[1]
We tentatively attributed the peculiar decrease in abundance of interferon-inducible transcripts observed at days 3 and 14 following administration of the third dose of the vaccine to the possible elicitation of an IgE response in a subset of individuals that failed to be protected by vaccination
Despite the pre-immune status, as was previously reported with IgGs36, we found the RTS,S vaccine to be a potent inducer of IgE responses
Summary
About 3.4 billion people, nearly half of the world’s population, live in areas at risk of Plasmodium transmission[1]. Significant advances over the past years have been made towards the development of an effective malaria vaccine[5] Most notably this includes successful testing of a live vaccine consisting of radiation-attenuated sporozoites[6], and this year licensure by regulatory authorities of the first malaria vaccine, the recombinant adjuvanted vaccine developed by global pharmaceutical GSK, called RTS,S known by its commercial name, Mosquirix®. This is a highly significant landmark but the efficacy of the vaccine for unknown reasons, and despite optimization attempts, remains suboptimal[7,8]. Downstream investigations identified a potential role for IgE responses of restricted specificity in mediating susceptibility to malaria infection
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