PMID- 30629148
OWN - NLM
STAT- MEDLINE
DCOM- 20200914
LR  - 20200914
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Print)
IS  - 1058-4838 (Linking)
VI  - 69
IP  - 9
DP  - 2019 Oct 15
TI  - First-in-human, Randomized, Double-blind Clinical Trial of Differentially 
      Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria.
PG  - 1509-1516
LID - 10.1093/cid/ciy1140 [doi]
AB  - BACKGROUND: Malaria in pregnancy has major impacts on mother and child health. To 
      complement existing interventions, such as intermittent preventive treatment and 
      use of impregnated bed nets, we developed a malaria vaccine candidate with the 
      aim of reducing sequestration of asexual "blood-stage" parasites in the placenta, 
      the major virulence mechanism. METHODS: The vaccine candidate PAMVAC is based on 
      a recombinant fragment of VAR2CSA, the Plasmodium falciparum protein responsible 
      for binding to the placenta via chondroitin sulfate A (CSA). Healthy, adult 
      malaria-naive volunteers were immunized with 3 intramuscular injections of 20 mug 
      (n = 9) or 50 mug (n = 27) PAMVAC, adjuvanted with Alhydrogel or glucopyranosyl 
      lipid adjuvant in stable emulsion (GLA-SE) or in a liposomal formulation with 
      QS21 (GLA-LSQ). Allocation was random and double blind. The vaccine was given 
      every 4 weeks. Volunteers were observed for 6 months following last immunization. 
      RESULTS: All PAMVAC formulations were safe and well tolerated. A total of 262 
      adverse events (AEs) occurred, 94 (10 grade 2 and 2 grade 3) at least possibly 
      related to the vaccine. No serious AEs occurred. Distribution and severity of AEs 
      were similar in all arms. PAMVAC was immunogenic in all participants. 
      PAMVAC-specific antibody levels were highest with PAMVAC-GLA-SE. The antibodies 
      inhibited binding of VAR2CSA expressing P. falciparum-infected erythrocytes to 
      CSA in a standardized functional assay. CONCLUSIONS: PAMVAC formulated with 
      Alhydrogel or GLA-based adjuvants was safe, well tolerated, and induced 
      functionally active antibodies. Next, PAMVAC will be assessed in women before 
      first pregnancies in an endemic area. CLINICAL TRIALS REGISTRATION: EudraCT 
      2015-001827-21; ClinicalTrials.gov NCT02647489.
CI  - (c) The Author(s) 2019. Published by Oxford University Press for the Infectious 
      Diseases Society of America.
FAU - Mordmuller, Benjamin
AU  - Mordmuller B
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
AD  - Centre de Recherches Medicales de Lambarene, Gabon.
FAU - Sulyok, Mihaly
AU  - Sulyok M
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
FAU - Egger-Adam, Diane
AU  - Egger-Adam D
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
FAU - Resende, Mafalda
AU  - Resende M
AD  - Centre for Medical Parasitology at Department of Immunology and Microbiology, 
      University of Copenhagen and Department of Infectious Diseases, Copenhagen 
      University Hospital.
FAU - de Jongh, Willem A
AU  - de Jongh WA
AD  - ExpreS2ion Biotechnologies, Horsholm, Denmark.
FAU - Jensen, Mette H
AU  - Jensen MH
AD  - Centre for Medical Parasitology at Department of Immunology and Microbiology, 
      University of Copenhagen and Department of Infectious Diseases, Copenhagen 
      University Hospital.
FAU - Smedegaard, Helle Holm
AU  - Smedegaard HH
AD  - Centre for Medical Parasitology at Department of Immunology and Microbiology, 
      University of Copenhagen and Department of Infectious Diseases, Copenhagen 
      University Hospital.
FAU - Ditlev, Sisse B
AU  - Ditlev SB
AD  - Centre for Medical Parasitology at Department of Immunology and Microbiology, 
      University of Copenhagen and Department of Infectious Diseases, Copenhagen 
      University Hospital.
FAU - Soegaard, Max
AU  - Soegaard M
AD  - ExpreS2ion Biotechnologies, Horsholm, Denmark.
FAU - Poulsen, Lars
AU  - Poulsen L
AD  - ExpreS2ion Biotechnologies, Horsholm, Denmark.
FAU - Dyring, Charlotte
AU  - Dyring C
AD  - ExpreS2ion Biotechnologies, Horsholm, Denmark.
FAU - Calle, Carlos Lamsfus
AU  - Calle CL
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
FAU - Knoblich, Annette
AU  - Knoblich A
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
FAU - Ibanez, Javier
AU  - Ibanez J
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
FAU - Esen, Meral
AU  - Esen M
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
AD  - Centre de Recherches Medicales de Lambarene, Gabon.
FAU - Deloron, Philippe
AU  - Deloron P
AD  - Mere et Enfant face aux Infections Tropicales, Institut de Recherche pour le 
      Developpement, Universite Paris 5, Sorbonne Paris Cite, France.
FAU - Ndam, Nicaise
AU  - Ndam N
AD  - Mere et Enfant face aux Infections Tropicales, Institut de Recherche pour le 
      Developpement, Universite Paris 5, Sorbonne Paris Cite, France.
FAU - Issifou, Saadou
AU  - Issifou S
AD  - Fondation pour la Recherche Scientifique and Institut de Recherche Clinique du 
      Benin, Cotonou.
FAU - Houard, Sophie
AU  - Houard S
AD  - European Vaccine Initiative, Heidelberg, Germany.
FAU - Howard, Randall F
AU  - Howard RF
AD  - Infectious Disease Research Institute, Seattle, Washington.
FAU - Reed, Steven G
AU  - Reed SG
AD  - Infectious Disease Research Institute, Seattle, Washington.
FAU - Leroy, Odile
AU  - Leroy O
AD  - European Vaccine Initiative, Heidelberg, Germany.
FAU - Luty, Adrian J F
AU  - Luty AJF
AD  - Mere et Enfant face aux Infections Tropicales, Institut de Recherche pour le 
      Developpement, Universite Paris 5, Sorbonne Paris Cite, France.
FAU - Theander, Thor G
AU  - Theander TG
AD  - Centre for Medical Parasitology at Department of Immunology and Microbiology, 
      University of Copenhagen and Department of Infectious Diseases, Copenhagen 
      University Hospital.
FAU - Kremsner, Peter G
AU  - Kremsner PG
AD  - Institut fur Tropenmedizin, Universitatsklinikum Tubingen and Deutsches Zentrum 
      fur Infektionsforschung, Germany.
AD  - Centre de Recherches Medicales de Lambarene, Gabon.
FAU - Salanti, Ali
AU  - Salanti A
AD  - Centre for Medical Parasitology at Department of Immunology and Microbiology, 
      University of Copenhagen and Department of Infectious Diseases, Copenhagen 
      University Hospital.
FAU - Nielsen, Morten A
AU  - Nielsen MA
AD  - Centre for Medical Parasitology at Department of Immunology and Microbiology, 
      University of Copenhagen and Department of Infectious Diseases, Copenhagen 
      University Hospital.
LA  - eng
SI  - ClinicalTrials.gov/NCT02647489
SI  - EudraCT/2015-001827-21
PT  - Clinical Trial, Phase I
PT  - Journal Article
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 (Liposomes)
RN  - 0 (Malaria Vaccines)
RN  - 5QB0T2IUN0 (Aluminum Hydroxide)
RN  - 9007-28-7 (Chondroitin Sulfates)
SB  - IM
MH  - Adult
MH  - Aluminum Hydroxide/chemistry
MH  - Chondroitin Sulfates/metabolism
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Injections, Intramuscular
MH  - Liposomes/chemistry
MH  - Malaria Vaccines/administration & dosage/*therapeutic use
MH  - Plasmodium falciparum/immunology/pathogenicity
MH  - Pregnancy
MH  - Young Adult
PMC - PMC6792113
OTO - NOTNLM
OT  - VAR2CSA
OT  - first-in-human
OT  - malaria vaccine
OT  - phase 1 clinical trial
OT  - pregnancy-associated malaria
EDAT- 2019/01/11 06:00
MHDA- 2020/09/15 06:00
PMCR- 2019/01/10
CRDT- 2019/01/11 06:00
PHST- 2018/08/17 00:00 [received]
PHST- 2019/01/03 00:00 [accepted]
PHST- 2019/01/11 06:00 [pubmed]
PHST- 2020/09/15 06:00 [medline]
PHST- 2019/01/11 06:00 [entrez]
PHST- 2019/01/10 00:00 [pmc-release]
AID - 5281109 [pii]
AID - ciy1140 [pii]
AID - 10.1093/cid/ciy1140 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2019 Oct 15;69(9):1509-1516. doi: 10.1093/cid/ciy1140.