Publications des scientifiques de l'IRD

Mordmuller B., Sulyok M., Egger-Adam D., Resende M., de Jongh W. A., Jensen M. H., Smedegaard H. H., Ditlev S. B., Soegaard M., Poulsen L., Dyring C., Calle C. L., Knoblich A., Ibanez J., Esen M., Deloron Philippe, Ndam N., Issifou S., Houard S., Howard R. F., Reed S. G., Leroy O., Luty Adrian, Theander T. G., Kremsner P. G., Salanti A., Nielsen M. A. (2019). First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria. Clinical Infectious Diseases, 69 (9), p. 1509-1516. ISSN 1058-4838.

Titre du document
First-in-human, randomized, double-blind clinical trial of differentially adjuvanted PAMVAC, a vaccine candidate to prevent pregnancy-associated malaria
Année de publication
2019
Type de document
Article référencé dans le Web of Science WOS:000491239500007
Auteurs
Mordmuller B., Sulyok M., Egger-Adam D., Resende M., de Jongh W. A., Jensen M. H., Smedegaard H. H., Ditlev S. B., Soegaard M., Poulsen L., Dyring C., Calle C. L., Knoblich A., Ibanez J., Esen M., Deloron Philippe, Ndam N., Issifou S., Houard S., Howard R. F., Reed S. G., Leroy O., Luty Adrian, Theander T. G., Kremsner P. G., Salanti A., Nielsen M. A.
Source
Clinical Infectious Diseases, 2019, 69 (9), p. 1509-1516 ISSN 1058-4838
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.
Plan de classement
Santé : généralités [050] ; Entomologie médicale / Parasitologie / Virologie [052]
Description Géographique
ALLEMAGNE ; TUBINGEN ; BENIN ; COTONOU
Localisation
Fonds IRD [F B010077138]
Identifiant IRD
fdi:010077138
Contact