PMID- 29945169
OWN - NLM
STAT- MEDLINE
DCOM- 20200305
LR  - 20200305
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 68
IP  - 3
DP  - 2019 Jan 18
TI  - 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.
PG  - 466-474
LID - 10.1093/cid/ciy514 [doi]
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 mug), 
      adjuvanted with Alhydrogel or glucopyranosil lipid adjuvant stable emulsion 
      (GLA-SE; 2.5 or 5 mug), 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. 
      CLINICAL TRIALS REGISTRATION: NCT01949909, PACTR201310000683408.
FAU - Steiner-Monard, Viviane
AU  - Steiner-Monard V
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Kamaka, Kassim
AU  - Kamaka K
AD  - Ifakara Health Institute, Bagamoyo, Tanzania.
FAU - Karoui, Olfa
AU  - Karoui O
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Roethlisberger, Samuel
AU  - Roethlisberger S
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Audran, Regine
AU  - Audran R
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Daubenberger, Claudia
AU  - Daubenberger C
AD  - Swiss Tropical and Public Health Institute, Basel.
FAU - Fayet-Mello, Aurelie
AU  - Fayet-Mello A
AD  - Clinical Trial Unit, CHUV, Lausanne.
FAU - Erdmann-Voisin, Aude
AU  - Erdmann-Voisin A
AD  - Clinical Trial Unit, CHUV, Lausanne.
FAU - Felger, Ingrid
AU  - Felger I
AD  - Swiss Tropical and Public Health Institute, Basel.
FAU - Geiger, Kristina
AU  - Geiger K
AD  - Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
FAU - Govender, Lerisa
AU  - Govender L
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Houard, Sophie
AU  - Houard S
AD  - European Vaccine Initiative, Heidelberg, Germany.
FAU - Huber, Eric
AU  - Huber E
AD  - Swiss Tropical and Public Health Institute, Basel.
FAU - Mayor, Carole
AU  - Mayor C
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Mkindi, Catherine
AU  - Mkindi C
AD  - Swiss Tropical and Public Health Institute, Basel.
FAU - Portevin, Damien
AU  - Portevin D
AD  - Swiss Tropical and Public Health Institute, Basel.
FAU - Rusch, Sebastian
AU  - Rusch S
AD  - Swiss Tropical and Public Health Institute, Basel.
FAU - Schmidlin, Sandro
AU  - Schmidlin S
AD  - Swiss Tropical and Public Health Institute, Basel.
FAU - Tiendrebeogo, Regis W
AU  - Tiendrebeogo RW
AD  - Department for Congenital Disorders, Statens Serum Institut, Denmark.
AD  - Centre for Medical Parasitology, University of Copenhagen, Denmark.
AD  - Department of Infectious Diseases, Copenhagen University Hospital, 
      Rigshospitalet, Denmark.
FAU - Theisen, Michael
AU  - Theisen M
AD  - Department for Congenital Disorders, Statens Serum Institut, Denmark.
AD  - Centre for Medical Parasitology, University of Copenhagen, Denmark.
AD  - Department of Infectious Diseases, Copenhagen University Hospital, 
      Rigshospitalet, Denmark.
FAU - Thierry, Anne-Christine
AU  - Thierry AC
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Vallotton, Laure
AU  - Vallotton L
AD  - Clinical Trial Unit, CHUV, Lausanne.
FAU - Corradin, Giampietro
AU  - Corradin G
AD  - Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
FAU - Leroy, Odile
AU  - Leroy O
AD  - European Vaccine Initiative, Heidelberg, Germany.
FAU - Abdulla, Salim
AU  - Abdulla S
AD  - Ifakara Health Institute, Bagamoyo, Tanzania.
FAU - Shekalaghe, Seif
AU  - Shekalaghe S
AD  - Ifakara Health Institute, Bagamoyo, Tanzania.
FAU - Genton, Blaise
AU  - Genton B
AD  - Swiss Tropical and Public Health Institute, Basel.
AD  - Policlinique medicale universitaire, Lausanne, Switzerland.
AD  - Infectious Disease Service, CHUV, Lausanne, Switzerland.
FAU - Spertini, Francois
AU  - Spertini F
AD  - Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois 
      (CHUV), Lausanne, Switzerland.
FAU - Jongo, Said A
AU  - Jongo SA
AD  - Ifakara Health Institute, Bagamoyo, Tanzania.
LA  - eng
SI  - ClinicalTrials.gov/NCT01949909
SI  - PACTR/PACTR201310000683408
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Protozoan)
RN  - 0 (Glucosides)
RN  - 0 (Lipid A)
RN  - 0 (Malaria Vaccines)
RN  - 0 (Vaccines, Synthetic)
RN  - 0 (glucopyranosyl lipid-A)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Adolescent
MH  - Adult
MH  - Aluminum Hydroxide/administration & dosage
MH  - Antibodies, Protozoan/*blood
MH  - Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology
MH  - Female
MH  - Glucosides/administration & dosage
MH  - Healthy Volunteers
MH  - Humans
MH  - Injections, Intramuscular
MH  - Lipid A/administration & dosage
MH  - Malaria Vaccines/administration & dosage/adverse effects/*immunology
MH  - Malaria, Falciparum/*prevention & control
MH  - Male
MH  - Middle Aged
MH  - Plasmodium falciparum
MH  - Switzerland
MH  - Tanzania
MH  - Vaccines, Synthetic/administration & dosage/adverse effects/immunology
MH  - Young Adult
EDAT- 2018/06/27 06:00
MHDA- 2020/03/07 06:00
CRDT- 2018/06/27 06:00
PHST- 2018/01/19 00:00 [received]
PHST- 2018/06/25 00:00 [accepted]
PHST- 2018/06/27 06:00 [pubmed]
PHST- 2020/03/07 06:00 [medline]
PHST- 2018/06/27 06:00 [entrez]
AID - 5045203 [pii]
AID - 10.1093/cid/ciy514 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2019 Jan 18;68(3):466-474. doi: 10.1093/cid/ciy514.