Decrease in circulating CD25hiFoxp3+ regulatory T cells following vaccination with the candidate malaria vaccine RTS, S. Issue 38 (31st August 2016)

• Record Type: Journal Article
• Authors: Parsons, Emily; Epstein, Judith; Sedegah, Martha; Villasante, Eileen; Stewart, Ann
• Is Part Of: Vaccine. Volume 34:Issue 38(2016)
• Page Start: 4618
• Page End: 4625
• Publication Date: 2016-08-31
• Subjects: Malaria vaccine -- RTS, S -- Heterologous prime-boost -- Plasmodium falciparum -- Circumsporozoite protein -- Regulatory T cell; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2016.07.008
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Decrease in CD25 hi Foxp3 + regulatory T cells with RTS, S vaccination. Decrease in markers of regulation and exhaustion with RTS, S vaccination. HBsAg vaccine backbone-specific IL-10 inversely correlates with malaria-specific IFN-γ. Heterologous prime-boost regimen does not change vaccine effect on Treg cells. Diversity in timing of peak vaccine response. Abstract: Regulatory T (Treg) cells have been shown in some cases to limit vaccine-specific immune responses and impact efficacy. Very little is known about the regulatory responses to the leading malaria vaccine candidate, RTS, S. The goal of this study was to begin to characterize the regulatory responses to the RTS, S vaccine. Using multi-parameter flow cytometry, we examined responses in 13 malaria naïve adult volunteers who received 2 doses of RTS, S given eight weeks apart. Five of these volunteers had previously received 3 doses of a candidate DNA-CSP vaccine, with the final dose given approximately one year prior to the first dose of the RTS, S vaccine. We found that the frequency of CD25 hi Foxp3 + Treg cells decreased following administration of RTS, S ( p = 0.0195), with no differences based on vaccine regimen. There was a concomitant decrease in CTLA-4 expression on CD25 hi Foxp3 + Treg cells ( p = 0.0093) and PD-1 levels on CD8 + T cells ( p = 0.0002). Additionally, the frequency of anergic CTLA-4 + CCR7 + T cells decreased following vaccination. An inverse correlation was observed between the frequency of Plasmodium falciparum circumsporozoite protein (PfCSP)-specific IFN-γ and PfCSP-specific IL-10, as well as an inverse correlation between IL-10 induced by Hepatitis B surface antigen, the carrier of RTS, S, and PfCSP-specific IFN-γ, suggesting that immunity against the vaccine backbone could impact vaccine immunogenicity. These results have implications for future malaria vaccine design.