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

Q1 · MEDICINE

Article

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

BackgroundP27A is an unstructured 104mer synthetic peptide from Plasmodium falciparum trophozoite exported protein 1 (TEX1), the target of human antibodies inhibiting parasite growth. The present project aimed at evaluating the safety and immunogenicity of P27A peptide vaccine in malaria-nonexposed European and malaria-exposed African adults.MethodsThis study was designed as a staggered, fast-track, randomized, antigen and adjuvant dose-finding, multicenter phase 1a/1b trial, conducted in Switzerland and Tanzania. P27A antigen (10 or 50 μg), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 μg), or control rabies vaccine (Verorab) were administered intramuscularly to 16 malaria-nonexposed and 40 malaria-exposed subjects on days 0, 28, and 56. Local and systemic adverse events (AEs) as well as humoral and cellular immune responses were assessed after each injection and during the 34-week follow-up.ResultsMost AEs were mild to moderate and resolved completely within 48 hours. Systemic AEs were more frequent in the formulation with alum as compared to GLA-SE, whereas local AEs were more frequent after GLA-SE. No serious AEs occurred. Supported by a mixed Th1/Th2 cell-mediated immunity, P27A induced a marked specific antibody response able to recognize TEX1 in infected erythrocytes and to inhibit parasite growth through an antibody-dependent cellular inhibition mechanism. Incidence of AEs and antibody responses were significantly lower in malaria-exposed Tanzanian subjects than in nonexposed European subjects.ConclusionsThe candidate vaccine P27A was safe and induced a particularly robust immunogenic response in combination with GLA-SE. This formulation should be considered for future efficacy trials.Clinical Trials RegistrationNCT01949909, PACTR201310000683408.

Frontiers in ImmunologyQ2 · MEDICINE

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

Q2 · MEDICINE

ArticleOA

Author: Correia, Bruno E ; Mkindi, Catherine ; Geiger, Kristina M ; Corradin, Giampietro ; Spertini, François ; Bikorimana, Jean-Pierre ; Yang, Che ; Guignard, Daniel ; Audran, Régine ; Daubenberger, Claudia A ; Houard, Sophie

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.

100 Deals associated with Antigenic polypeptide vaccine pf27(University of Lausanne)

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Indication	Highest Phase	Country/Location	Organization	Date
Malaria, Falciparum	Phase 1	-	University of Lausanne	-

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Antigenic polypeptide vaccine pf27(University of Lausanne)

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