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First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria
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” par...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792113/ https://www.ncbi.nlm.nih.gov/pubmed/30629148 http://dx.doi.org/10.1093/cid/ciy1140 |
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author | 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 |
author_facet | 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 |
author_sort | Mordmüller, Benjamin |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6792113 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67921132019-10-18 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 Clin Infect Dis Articles and Commentaries 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. Oxford University Press 2019-11-01 2019-01-10 /pmc/articles/PMC6792113/ /pubmed/30629148 http://dx.doi.org/10.1093/cid/ciy1140 Text en © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles and Commentaries 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 First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria |
title | First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria |
title_full | First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria |
title_fullStr | First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria |
title_full_unstemmed | First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria |
title_short | First-in-human, Randomized, Double-blind Clinical Trial of Differentially Adjuvanted PAMVAC, A Vaccine Candidate to Prevent Pregnancy-associated Malaria |
title_sort | first-in-human, randomized, double-blind clinical trial of differentially adjuvanted pamvac, a vaccine candidate to prevent pregnancy-associated malaria |
topic | Articles and Commentaries |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6792113/ https://www.ncbi.nlm.nih.gov/pubmed/30629148 http://dx.doi.org/10.1093/cid/ciy1140 |
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