Posted in Malaria, Resource

Expression of genes associated with immunoproteasome processing of major histocompatibility complex peptides is indicative of protection with adjuvanted RTS,S malaria vaccine

Figure highlighting that subjects with increased expression of genes involved in formation of the immunoproteasome complex after RTS,S vaccination are associated with increased protection from malaria challenge. Specific genes involved highlighted in red. Source from MT Vahey, JID, 2010.

The RTS,S is a subunit recombinant vaccine expressed in yeast that represents the central repeat and C-terminal portion of the Plasmodium falciparum circumsporozoite protein (CSP) covalently linked with the S antigen of hepatitis B virus. The overall protective efficacy of RTS,S/ASO1B in malaria-naive adults is ∼50%.

The differences in the spectrum of the protective responses to adjuvanted RTS,S, and the ability to do an experimental challenge with the mosquito-borne falciparum malaria, offers an opportunity to decipher the host genomic mechanisms involved in vaccine efficacy against malaria.

In this study by MT Vahey et al., 2010, 39 vaccine recipients were assessed at study entry, on the day of the third vaccination, at 24 h, 72 h, and 2 weeks after vaccination, and on day 5 after challenge. Of 39 vaccine recipients, 13 were protected and 26 were not.

Most DEGs were detected at day 1 post vaccination, with the majority of these transcripts associated with proinflammatory responses. Most of these responses resolve at day 3 post-vaccination.

After day 5 of malaria challenge, prediction analysis of microarray (PAMR) identified 393 genes that are differentially expressed in subjects who are protected and unprotected. Most of these genes are related to apoptosis and cell cycle.

At 2 weeks after the third vaccination but before malaria challenge, 32 genes belonging to the proteasome degradation pathway separated protected vs unprotected subjects. Examples include PSME2 (a component of the 11S regulator), and PSMA4, PSMB6, and PSMB9 which forms the immunoproteasome involved in processesing of peptides for presentation to the MHC complex.

This study may highlight the critical role of T-cells as correlate of protection against malaria. Data deposited at Gene Expression Omnibus, with accession number GSE18323.

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