The Candidate Blood-stage Malaria Vaccine P27A Induces a Robust Humoral Response in a Fast Track to the Field Phase 1 Trial in Exposed and Nonexposed Volunteers

Steiner-Monard, Viviane; Kamaka, Kassim; Karoui, Olfa; Roethlisberger, Samuel; Audran, R; Daubenberger, Claudia; Fayet-Mello, Aurélie; Erdmann-Voisin, Aude; Felger, Ingrid; Geiger, Kristina; Govender, Lerisa; Houard, Sophie; Huber, Eric; Mayor, Claire; Mkindi, Catherine; Portevin, Damien; Rusch, Sebastian; Schmidlin, Sandro; Tiendrebeogo, Régis Wendpayangde; Theisen, Michael; Thierry, Anne‐Christine; Vallotton, Laurent; Corradin, Giampietro; Leroy, Odile; Abdulla, Salim; Shekalaghe, Seif; Genton, Blaise; Spertini, François; Jongo, Said

doi:10.1093/cid/ciy514

Cited by 28 publications

(29 citation statements)

References 20 publications

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“…We previously reported that GLA-SE formulation induced higher anti-P27A titers than Alum, and that pre-exposed subjects exhibited lower humoral responses as compared to unexposed subjects. Furthermore, an increase in the dose of GLA-SE in the vaccine formulation was associated with an increase in antibody titers (5,15). We observed that the antibody responses directed to the 20-mer peptides had the same intensity profile as anti-P27A.…”

Section: Antibody Response and Fine-specificitymentioning

confidence: 70%

“…P27A formulated in Alum or in GLA-SE was studied in parallel in a phase 1a clinical trial in Lausanne, Switzerland (CH) and in a 1b clinical trial in Bagamoyo, Tanzania (TZ) (15). Trials were registered in clinicaltrials.gov (NCT01949909) and www.…”

Section: Human Samplesmentioning

confidence: 99%

“…The immunoglobulin G (IgG) immune response against the synthetic P27A and overlapping 20-mers was measured using an enzyme-linked immunosorbent assay (ELISA) (5,15). Microtiter plates (Nunc TM Maxisorp, Denmark) were coated at a concentration of 2 and 5 µg/mL, respectively, at RT for 1 h then blocked with PBS-3% milk for 1 h. Samples and controls were serially diluted in PBS-1.5% milk-0-05% Tween and added at 50 µL per well.…”

Section: Humoral Responsementioning

confidence: 99%

“…Peptide vaccines induce a direct, strong immune response, and are cost-effective and easy to produce and store (12)(13)(14). Due to the promising properties of P27A as an anti-malaria vaccine candidate, phase 1a and 1b clinical trials were performed in malaria unexposed subjects from Switzerland (CH) and in malaria pre-exposed healthy adults from Tanzania (TZ) to evaluate its safety and immunogenic properties in combination with adjuvants Alhydrogel or glucopyranosyl lipid A in a stable emulsion (GLA-SE) (15). The vaccine was safe and induced a strong humoral response, particularly in combination with GLA-SE, and was active in inhibiting in vitro parasite growth (15).…”

Section: Introductionmentioning

confidence: 99%

“…Due to the promising properties of P27A as an anti-malaria vaccine candidate, phase 1a and 1b clinical trials were performed in malaria unexposed subjects from Switzerland (CH) and in malaria pre-exposed healthy adults from Tanzania (TZ) to evaluate its safety and immunogenic properties in combination with adjuvants Alhydrogel or glucopyranosyl lipid A in a stable emulsion (GLA-SE) (15). The vaccine was safe and induced a strong humoral response, particularly in combination with GLA-SE, and was active in inhibiting in vitro parasite growth (15). In this report, we characterized the anti-P27A cellular and humoral responses generated in vaccinated subjects, particularly the fine specificity and IgG affinities.…”

Section: Introductionmentioning

confidence: 99%

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Epitope Mapping and Fine Specificity of Human T and B Cell Responses for Novel Candidate Blood-Stage Malaria Vaccine P27A

et al. 2020

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P27A is a novel synthetic malaria vaccine candidate derived from the blood stage Plasmodium falciparum protein Trophozoite Exported Protein 1 (TEX1/PFF0165c). In phase 1a/1b clinical trials in malaria unexposed adults in Switzerland and in malaria pre-exposed adults in Tanzania, P27A formulated with Alhydrogel and GLA-SE adjuvants induced antigen-specific antibodies and T-cell activity. The GLA-SE adjuvant induced significantly stronger humoral responses than the Alhydrogel adjuvant. Groups of pre-exposed and unexposed subjects received identical vaccine formulations, which supported the comparison of the cellular and humoral response to P27A in terms of fine specificity and affinity for populations and adjuvants. Globally, fine specificity of the T and B cell responses exhibited preferred recognized sequences and did not highlight major differences between adjuvants or populations. Affinity of anti-P27A antibodies was around 10 −8 M in all groups. Pre-exposed volunteers presented anti-P27A with higher affinity than unexposed volunteers. Increasing the dose of GLA-SE from 2.5 to 5 µg in pre-exposed volunteers improved anti-P27A affinity and decreased the number of recognized epitopes. These results indicate a higher maturation of the humoral response in pre-exposed volunteers, particularly when immunized with P27A formulated with 5 µg GLA-SE.

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Section: Antibody Response and Fine-specificitymentioning

confidence: 70%

Section: Human Samplesmentioning

confidence: 99%

Section: Humoral Responsementioning

confidence: 99%