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- Title
First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria.
- Authors
Mordmüller, Benjamin; Sulyok, Mihály; Egger-Adam, Diane; Resende, Mafalda; Jongh, Willem A de; 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
- Abstract
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.
- Subjects
MALARIA prevention; VACCINES; ERYTHROCYTES; EMULSIONS; IMMUNIZATION; IMMUNOGLOBULINS; INTRAMUSCULAR injections; PARASITIC diseases in pregnancy; PLACENTA; PROTOZOA; RANDOMIZED controlled trials; CHONDROITIN sulfates; SEVERITY of illness index
- Publication
Clinical Infectious Diseases, 2019, Vol 69, Issue 9, p1509
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciy1140