Induction of Plasmodium falciparum-Specific CD4+ T Cells and Memory B Cells in Gabonese Children Vaccinated with RTS,S/AS01E and RTS,S/AS02D

Agnandji, Selidji Todagbé; Fendel, Rolf; Mestre, M. P. Diaz; Janssens, Michel; Vekemans, Johan; Held, Jana; Gnansounou, Ferdinand; Haertle, Sonja; Glasenapp, Isabel von; Oyakhirome, Sunny; Mewono, Ludovic; Moris, Philippe; Lievens, Marc; Demoitié, Marie-Ange; Dubois, Patrice; Villafana, Tonya; Jongert, Erik; Olivier, Aurélie; Cohen, Joe; Esen, Meral; Kremsner, Peter G.; Lell, Bertrand; Mordmüller, Benjamin

doi:10.1371/journal.pone.0018559

Cited by 44 publications

(35 citation statements)

References 51 publications

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“…Induction of CD4 + T cells directed against P. falciparum CS protein by RTS,S adjuvanted formulations has been shown in clinical field trials in adults and children. 6,8,9,[21][22][23] No systematic vaccine-induced CD8 + T cell response was detected in PBMCs in our study, which was consistent with other studies that showed RTS,S/AS induces little or no detectable CD8 + T cell response. 6,11,21,24,25 The anti-CS humoral immune responses in this study tended to be lower than those observed following administration of 3 doses of RTS,S/AS01 or RTS,S/AS02 to malaria-experienced children in Africa 13,14 but higher than those in African adults in a high malaria transmission area.…”

Section: Discussionsupporting

confidence: 91%

“…[5][6][7] CS-specific CD4 + T cells induced by RTS,S produce a mixture of cytokines, such as interleukin (IL)-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. [7][8][9][10][11] In phase 2 clinical trials of adults and children, the RTS,S/AS01 formulation had an improved immunogenicity profile, in terms of humoral and cell-mediated immune (CMI) responses, and an equally favorable safety profile as compared with RTS,S/AS02. [11][12][13][14] The RTS,S/AS01 formulation was…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines

Leroux‐Roels

Leroux-Roels

Clement

et al. 2014

Human Vaccines & Immunotherapeutics

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines

Leroux‐Roels

Leroux-Roels

Clement

et al. 2014

Human Vaccines & Immunotherapeutics

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“…In the human host this protein is mainly expressed in the late plasmodial stages, i.e. in late trophozoites and schizonts232425. Initially, the 83-kDa precursor of AMA1 (AMA1 83 ) is localized in the micronemes2627.…”

mentioning

confidence: 99%

Characterization of a novel inhibitory human monoclonal antibody directed against Plasmodium falciparum Apical Membrane Antigen 1

Maskus

Królik

Bethke

et al. 2016

Sci Rep

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Malaria remains a major challenge to global health causing extensive morbidity and mortality. Yet, there is no efficient vaccine and the immune response remains incompletely understood. Apical Membrane Antigen 1 (AMA1), a leading vaccine candidate, plays a key role during merozoite invasion into erythrocytes by interacting with Rhoptry Neck Protein 2 (RON2). We generated a human anti-AMA1-antibody (humAbAMA1) by EBV-transformation of sorted B-lymphocytes from a Ghanaian donor and subsequent rescue of antibody variable regions. The antibody was expressed in Nicotiana benthamiana and in HEK239-6E, characterized for binding specificity and epitope, and analyzed for its inhibitory effect on Plasmodium falciparum. The generated humAbAMA1 shows an affinity of 106–135 pM. It inhibits the parasite strain 3D7A growth in vitro with an expression system-independent IC50-value of 35 μg/ml (95% confidence interval: 33 μg/ml–37 μg/ml), which is three to eight times lower than the IC50-values of inhibitory antibodies 4G2 and 1F9. The epitope was mapped to the close proximity of the RON2-peptide binding groove. Competition for binding between the RON2-peptide and humAbAMA1 was confirmed by surface plasmon resonance spectroscopy measurements. The particularly advantageous inhibitory activity of this fully human antibody might provide a basis for future therapeutic applications.

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“…The ICS assay on whole blood was previously developed and used in several clinical trials (Agnandji et al, 2011;Day et al, 2013;Harenberg et al, 2013). An advantage of using whole blood instead of PBMCs is the smaller sample volumes needed when blood is used without preliminary PBMC purification, making this type of assay particularly attractive in children, in settings where testing at frequent time intervals is planned or for trials conducted in areas with high HIV endemicity, where access to liquid nitrogen might be problematic (Agnandji et al, 2011;Mallone et al, 2011;Day et al, 2013;Harenberg et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naïve HIV-1-infected patients

Bourguignon¹,

Clement²,

Renaud³

et al. 2014

Journal of Immunological Methods

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Intracellular cytokine staining (ICS) assay is increasingly used in vaccine clinical trials to measure antigen-specific T-cell mediated immune (CMI) responses in cryopreserved peripheral blood mononuclear cells (PBMCs) and whole blood. However, recent observations indicate that several parameters involved in blood processing can impact PBMC viability and CMI responses, especially in antiretroviral therapy (ART)-naïve HIV-1-infected individuals. In this phase I study (NCT01610427), we collected blood samples from 22 ART-naïve HIV-1-infected adults. PBMCs were isolated and processed for ICS assay. The individual and combined effects of the following parameters were investigated: time between blood collection and PBMC processing (time-to-process: 2, 7 or 24 h); time between PBMC thawing and initiation of in vitro stimulation with HIV-1 antigens (resting-time: 0, 2, 6 and 18 h); and duration of antigen-stimulation in PBMC cultures (stimulation-time: 6h or overnight). The cell recovery after thawing, cell viability after ICS and magnitude of HIV-specific CD8(+) T-cell responses were considered to determine the optimal combination of process conditions. The impact of time-to-process (2 or 4 h) on HIV-specific CD8(+) T-cell responses was also assessed in a whole blood ICS assay. A higher quality of cells in terms of recovery and viability (up to 81% and >80% respectively) was obtained with shorter time-to-process (less than 7 h) and resting-time (less than 2 h) intervals. Longer (overnight) rather than shorter (6 h) stimulation-time intervals increased the frequency of CD8(+)-specific T-cell responses using ICS in PBMCs without change of the functionality. The CD8(+) specific T-cell responses detected using fresh whole blood showed a good correlation with the responses detected using frozen PBMCs. Our results support the need of standardized procedures for the evaluation of CMI responses, especially in HIV-1-infected, ART-naïve patients.

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Induction of Plasmodium falciparum-Specific CD4+ T Cells and Memory B Cells in Gabonese Children Vaccinated with RTS,S/AS01E and RTS,S/AS02D

Cited by 44 publications

References 51 publications

Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines

Evaluation of the immune response to RTS,S/AS01 and RTS,S/AS02 adjuvanted vaccines

Characterization of a novel inhibitory human monoclonal antibody directed against Plasmodium falciparum Apical Membrane Antigen 1

Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naïve HIV-1-infected patients

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