First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria
| العنوان: | First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria |
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| المؤلفون: | Max Soegaard, Annette Knoblich, Willem A. de Jongh, Peter G. Kremsner, Nicaise Tuikue Ndam, Steven G. Reed, Lars Poulsen, Mihály Sulyok, Morten Nielsen, Odile Leroy, Mafalda Resende, Carlos Lamsfus Calle, Javier Ibáñez, Meral Esen, Ali Salanti, Thor G. Theander, Saadou Issifou, Randall F. Howard, Helle Holm Smedegaard, Benjamin Mordmüller, Mette H Jensen, Philippe Deloron, Sophie Houard, Charlotte Dyring, Adrian J. F. Luty, Diane Egger-Adam, Sisse B. Ditlev |
| المصدر: | Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America Mordmüller, 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, Ibáñez, J, Esen, M, Deloron, P, Ndam, N, Issifou, S, Houard, S, Howard, R F, Reed, S G, Leroy, O, Luty, A J F, 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 : an official publication of the Infectious Diseases Society of America, vol. 69, no. 9, pp. 1509-1516 . https://doi.org/10.1093/cid/ciy1140Test |
| بيانات النشر: | Oxford University Press, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Microbiology (medical), malaria vaccine, Adult, medicine.medical_treatment, phase 1 clinical trial, Plasmodium falciparum, Aluminum Hydroxide, VAR2CSA, Injections, Intramuscular, 03 medical and health sciences, Young Adult, 0302 clinical medicine, first-in-human, Double-Blind Method, Pregnancy, parasitic diseases, Malaria Vaccines, medicine, pregnancy-associated malaria, Humans, 030212 general & internal medicine, Adverse effect, Articles and Commentaries, Pregnancy-associated malaria, biology, business.industry, Malaria vaccine, Chondroitin Sulfates, medicine.disease, biology.organism_classification, QS21, 3. Good health, 030104 developmental biology, Infectious Diseases, Immunology, Liposomes, Female, business, Adjuvant, Malaria |
| الوصف: | 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. The pregnancy-associated malaria-vaccine candidate PAMVAC is safe and well tolerated with all three tested formulations and induces functional binding-inhibitory antibodies. The vaccine with glucopyranosyl lipid adjuvant (GLA) in stable emulsion is superior to Alhydrogel and a GLA/QS21 liposomal formulation. |
| وصف الملف: | text/pdf; application/pdf |
| اللغة: | English |
| تدمد: | 1537-6591 1058-4838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c2527dce75d8d760dee04c009fb0a7b0Test http://europepmc.org/articles/PMC6792113Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c2527dce75d8d760dee04c009fb0a7b0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376591 10584838 |
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