Safety and Immunogenicity of ChAd63/MVA Pfs25-IMX313 in a Phase I First-in-Human Trial
| Autor: | Sarah E. Silk, Arianna Marini, Iona J. Taylor, Saul N. Faust, Nathan J Brendish, Simon J. Draper, Adrian V. S. Hill, Sean C. Elias, Filipa Martins, Rachel Roberts, Hans de Graaf, Angela M. Minassian, Fergal Hill, Johan Vekemans, Marija Zaric, Eleanor Berrie, Sarah Moyle, Sumi Biswas, Nick J. Edwards, Carol A Long, Diane Gbesemete, David Mekhaiel, Alison M. Lawrie, Megan Baker, Lee Li, Ian D. Poulton, Ruth O. Payne, Kazutoyo Miura |
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| Přispěvatelé: | Marini, Arianna [0000-0003-3416-7362], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Time Factors T-Lymphocytes Immunology Plasmodium falciparum malaria Antibodies Protozoan Viral vector 03 medical and health sciences chemistry.chemical_compound Complement inhibitor 0302 clinical medicine Immunogenicity Vaccine Antigen vaccine parasitic diseases Malaria Vaccines Immunology and Allergy Medicine Humans Orthopoxvirus Malaria Falciparum Cells Cultured Original Research Vaccines Synthetic Reactogenicity biology business.industry IMX313 Immunogenicity RC581-607 biology.organism_classification Virology Healthy Volunteers 030104 developmental biology Pfs25 chemistry England Immunization Immunologic diseases. Allergy Vaccinia business 030217 neurology & neurosurgery transmission-blocking |
| Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 12 (2021) |
| ISSN: | 1664-3224 |
| Popis: | BackgroundTransmission blocking vaccines targeting the sexual-stages of the malaria parasite could play a major role to achieve elimination and eradication of malaria. The Plasmodium falciparum Pfs25 protein (Pfs25) is the most clinically advanced candidate sexual-stage antigen. IMX313, a complement inhibitor C4b-binding protein that forms heptamers with the antigen fused to it, improve antibody responses. This is the first time that viral vectors have been used to induce antibodies in humans against an antigen that is expressed only in the mosquito vector.MethodsClinical trial looking at safety and immunogenicity of two recombinant viral vectored vaccines encoding Pfs25-IMX313 in healthy malaria-naive adults. Replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding Pfs25-IMX313, were delivered by the intramuscular route in a heterologous prime-boost regimen using an 8-week interval. Safety data and samples for immunogenicity assays were taken at various time-points.ResultsThe reactogenicity of the vaccines was similar to that seen in previous trials using the same viral vectors encoding other antigens. The vaccines were immunogenic and induced both antibody and T cell responses against Pfs25, but significant transmission reducing activity (TRA) was not observed in most volunteers by standard membrane feeding assay.ConclusionBoth vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. However, the transmission reducing activity of the antibodies generated were weak, suggesting the need for an alternative vaccine formulation.Trial RegistrationClinicaltrials.gov NCT02532049. |
| Databáze: | OpenAIRE |
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