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

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

doi:10.1093/cid/ciy514

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

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

14 Citations (Scopus)

Abstract

Background. P27A 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. Methods. This 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 ?g), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 ?g), 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. Results. Most 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. Conclusions. The 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.

Original language	English
Journal	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume	68
Issue number	3
Pages (from-to)	466-474
Number of pages	9
ISSN	1058-4838
DOIs	https://doi.org/10.1093/cid/ciy514
Publication status	Published - 18 Jan 2019

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Steiner-Monard, V., Kamaka, K., Karoui, O., Roethlisberger, S., Audran, R., Daubenberger, C., Fayet-Mello, A., Erdmann-Voisin, A., Felger, I., Geiger, K., Govender, L., Houard, S., Huber, E., Mayor, C., Mkindi, C., Portevin, D., Rusch, S., Schmidlin, S., Tiendrebeogo, R. W., ... Jongo, S. A. (2019). 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. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 68(3), 466-474. https://doi.org/10.1093/cid/ciy514

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 et al.
In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 68, No. 3, 18.01.2019, p. 466-474.

Research output: Contribution to journal › Journal article › Research › peer-review

Steiner-Monard, V, Kamaka, K, Karoui, O, Roethlisberger, S, Audran, R, Daubenberger, C, Fayet-Mello, A, Erdmann-Voisin, A, Felger, I, Geiger, K, Govender, L, Houard, S, Huber, E, Mayor, C, Mkindi, C, Portevin, D, Rusch, S, Schmidlin, S, Tiendrebeogo, RW , Theisen, M, Thierry, A-C, Vallotton, L, Corradin, G, Leroy, O, Abdulla, S, Shekalaghe, S, Genton, B, Spertini, F & Jongo, SA 2019, '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', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 68, no. 3, pp. 466-474. https://doi.org/10.1093/cid/ciy514

Steiner-Monard V, Kamaka K, Karoui O, Roethlisberger S, Audran R, Daubenberger C et al. 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. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2019 Jan 18;68(3):466-474. doi: 10.1093/cid/ciy514

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abstract = "Background. P27A 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. Methods. This 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 ?g), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 ?g), 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. Results. Most 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. Conclusions. The 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.",

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T1 - 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

AU - Steiner-Monard, Viviane

AU - Kamaka, Kassim

AU - Karoui, Olfa

AU - Roethlisberger, Samuel

AU - Audran, Régine

AU - Daubenberger, Claudia

AU - Fayet-Mello, Aurélie

AU - Erdmann-Voisin, Aude

AU - Felger, Ingrid

AU - Geiger, Kristina

AU - Govender, Lerisa

AU - Houard, Sophie

AU - Huber, Eric

AU - Mayor, Carole

AU - Mkindi, Catherine

AU - Portevin, Damien

AU - Rusch, Sebastian

AU - Schmidlin, Sandro

AU - Tiendrebeogo, Regis W

AU - Theisen, Michael

AU - Thierry, Anne-Christine

AU - Vallotton, Laure

AU - Corradin, Giampietro

AU - Leroy, Odile

AU - Abdulla, Salim

AU - Shekalaghe, Seif

AU - Genton, Blaise

AU - Spertini, François

AU - Jongo, Said A

PY - 2019/1/18

Y1 - 2019/1/18

N2 - Background. P27A 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. Methods. This 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 ?g), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 ?g), 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. Results. Most 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. Conclusions. The 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.

AB - Background. P27A 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. Methods. This 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 ?g), adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion (GLA-SE; 2.5 or 5 ?g), 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. Results. Most 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. Conclusions. The 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.

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DO - 10.1093/cid/ciy514

M3 - Journal article

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SN - 1058-4838

VL - 68

SP - 466

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JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

IS - 3

ER -

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

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