title: Decrease in circulating CD25(hi)Foxp3(+) regulatory T cells following vaccination with the candidate malaria vaccine RTS,S.
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.
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Parsons
authors.affiliation: Naval Medical Research Center, Silver Spring, MD, United States.
authors.forename: Judith
authors.initials: J
authors.lastname: Epstein
authors.affiliation: Naval Medical Research Center, Silver Spring, MD, United States.
authors.forename: Martha
authors.initials: M
authors.lastname: Sedegah
authors.affiliation: Naval Medical Research Center, Silver Spring, MD, United States.
authors.forename: Eileen
authors.initials: E
authors.lastname: Villasante
authors.affiliation: Uniformed Services University of the Health Sciences, Bethesda, MD, United States. Electronic address: ann.stewart@usuhs.edu.
authors.forename: Ann
authors.initials: A
authors.lastname: Stewart
mesh_terms: D000328:Adult; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D010865:Pilot Projects; D015800:Protozoan Proteins / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D006514:Hepatitis B Surface Antigens; C573415:IFNG protein, human; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: Circumsporozoite protein; Heterologous prime-boost; Malaria vaccine; Plasmodium falciparum; RTS,S; Regulatory T cell