First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria
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First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria. / Mordmüller, Benjamin; Sulyok, Mihály; Egger-Adam, Diane; Resende, Mafalda; de Jongh, Willem A; Jensen, Mette H.; Smedegaard, Helle Holm; Ditlev, Sisse B; Soegaard, Max; Poulsen, Lars; Dyring, Charlotte; Calle, Carlos Lamsfus; Knoblich, Annette; Ibáñez, Javier; Esen, Meral; Deloron, Philippe; Ndam, Nicaise; Issifou, Saadou; Houard, Sophie; Howard, Randall F; Reed, Steven G; Leroy, Odile; Luty, Adrian J F; Theander, Thor G; Kremsner, Peter G; Salanti, Ali; Nielsen, Morten A.
I: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Bind 69, Nr. 9, 2019, s. 1509-1516.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria
AU - Mordmüller, Benjamin
AU - Sulyok, Mihály
AU - Egger-Adam, Diane
AU - Resende, Mafalda
AU - de Jongh, Willem A
AU - Jensen, Mette H.
AU - Smedegaard, Helle Holm
AU - Ditlev, Sisse B
AU - Soegaard, Max
AU - Poulsen, Lars
AU - Dyring, Charlotte
AU - Calle, Carlos Lamsfus
AU - Knoblich, Annette
AU - Ibáñez, Javier
AU - Esen, Meral
AU - Deloron, Philippe
AU - Ndam, Nicaise
AU - Issifou, Saadou
AU - Houard, Sophie
AU - Howard, Randall F
AU - Reed, Steven G
AU - Leroy, Odile
AU - Luty, Adrian J F
AU - Theander, Thor G
AU - Kremsner, Peter G
AU - Salanti, Ali
AU - Nielsen, Morten A
N1 - © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.
PY - 2019
Y1 - 2019
N2 - 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 μg (n = 9) or 50 μg (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.
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 μg (n = 9) or 50 μg (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.
U2 - 10.1093/cid/ciy1140
DO - 10.1093/cid/ciy1140
M3 - Journal article
C2 - 30629148
VL - 69
SP - 1509
EP - 1516
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
SN - 1058-4838
IS - 9
ER -
ID: 228814489