%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Mordmuller, B.
%A Sulyok, M.
%A Egger-Adam, D.
%A Resende, M.
%A de Jongh, W. A.
%A Jensen, M. H.
%A Smedegaard, H. H.
%A Ditlev, S. B.
%A Soegaard, M.
%A Poulsen, L.
%A Dyring, C.
%A Calle, C. L.
%A Knoblich, A.
%A Ibanez, J.
%A Esen, M.
%A Deloron, Philippe
%A Ndam, N.
%A Issifou, S.
%A Houard, S.
%A Howard, R. F.
%A Reed, S. G.
%A Leroy, O.
%A Luty, Adrian
%A Theander, T. G.
%A Kremsner, P. G.
%A Salanti, A.
%A Nielsen, M. A.
%T First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria
%D 2019
%L fdi:010077138
%G ENG
%J Clinical Infectious Diseases
%@ 1058-4838
%K malaria vaccine ; VAR2CSA ; pregnancy-associated malaria ; first-in-human ; phase 1 clinical trial
%K ALLEMAGNE ; TUBINGEN ; BENIN ; COTONOU
%M ISI:000491239500007
%N 9
%P 1509-1516
%R 10.1093/cid/ciy1140
%U https://www.documentation.ird.fr/hor/fdi:010077138
%> https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers19-11/010077138.pdf
%V 69
%W Horizon (IRD)
%X 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 mu g (n = 9) or 50 mu g (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.
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