Superior antibody immunogenicity of a RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults
Superior antibody immunogenicity of a RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults
Abstract BackgroundRH5 is the leading blood-stage candidate antigen for inclusion in a Plasmodium falciparum malaria vaccine, however, its safety profile and ability to induce functional immune responses in a malaria-endemic population are unknown. Characterising safety and immunogenicity is key to refine and progress next-generation RH5-based blood-stage malaria vaccines to field efficacy assessment. MethodsA Phase 1b, single-center, dose-escalation, age de-escalation, double-blind, randomized, controlled trial was conducted in Bagamoyo, Tanzania. Healthy adults (18-35 years), young children (1-6 years) and infants (6-11 months) were recruited to receive a priming dose of viral-vectored ChAd63 RH5 (or rabies control vaccine) followed by a booster dose of MVA RH5 (or rabies control vaccine) 8 weeks later. The primary outcomes were the number of solicited and unsolicited adverse events following vaccination and the number of serious adverse events over the whole study period. Secondary outcomes included quantitative and qualitative measures of the anti-RH5 immune response. All participants receiving at least one dose of vaccine were included in the primary analyses. FindingsBetween 12th April and 25th October 2018 a total of 63 adults, children and infants were recruited and primed and 60 of these were boosted, all completing six months of follow-up post-priming vaccination. Vaccinations were well-tolerated with participants reporting predominantly mild reactogenicity, with profiles comparable between ChAd63 RH5, MVA RH5 and rabies vaccine groups, and across the age groups. No serious adverse events were reported during the study period. RH5-specific T cell, B cell and serum antibody responses were induced by vaccination. Higher anti-RH5 serum IgG responses were observed post-boost in the 1-6 year old children (median 93 μg/mL; range: 31-508 μg/mL) and infants (median 149 μg/mL; range: 29-352 μg/mL) as compared to adults (median 14 μg/mL; range: 9-15 μg/mL). These contracted over time post-boost, but the same hierarchy of responses across the age groups was maintained to end of follow-up at 16 weeks post-boost (day 168). Vaccine-induced anti-RH5 antibodies were functional showing growth inhibition activity (GIA) in vitro against P. falciparum blood-stage parasites. The highest levels were observed in the 6-11 month old infants, with 6/11 showing >60% GIA following dilution of total IgG to 2.5 mg/mL (median 61%; range: 41-78%). InterpretationThe ChAd63-MVA RH5 vaccine regimen shows an acceptable safety and reactogenicity profile and encouraging immunogenicity in children and infants residing in a malaria-endemic area. The levels of functional GIA observed in the RH5 vaccinated 6-11 month old infants are the highest levels reported to-date following human vaccination. These data support onward clinical development of RH5-based blood-stage vaccines that aim to protect against clinical malaria in young African infants. FundingMedical Research Council, London, United Kingdom. Trial RegistrationISRCTN registry: 47448832 and ClinicalTrials.gov: NCT03435874.
Minassian Angela M.、Milando Florence、Silk Sarah E.、Mtaka Ivanny M.、Mpina Maximillian、Simon Beatus、Athumani Thabit、Mswata Sarah、Wang Lawrence T.、Rashid Mohammed、Lweno Omary、Cho Jee-Sun、Nyaulingo Gloria、Long Carole A.、Nugent Fay L.、Ahmed Saumu、Mohammed Latipha、Nielsen Carolyn M.、Draper Simon J.、Lilolime Nasoro S.、Hodgson Susanne H.、King Lloyd D. W.、Barrett Jordan R.、Diouf Ababacar、Ali Ali M.、Payne Ruth O.、Olotu Ally I.、Mwamlima Tunu G.、Kalinga Wilmina F.、Mkwepu Fatuma、Mwalimu Bakari、Miura Kazutoyo、Themistocleous Yrene、Lawrie Alison M.
Department of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordInterventions and Clinical Trials Department, Ifakara Health InstituteDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteDepartment of Biochemistry, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordInterventions and Clinical Trials Department, Ifakara Health InstituteLaboratory of Malaria and Vector ResearchDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of OxfordInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordInterventions and Clinical Trials Department, Ifakara Health InstituteDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordDepartment of Biochemistry, University of Oxford||Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford||Kavli Institute for Nanoscience Discovery University of OxfordLaboratory of Malaria and Vector ResearchInterventions and Clinical Trials Department, Ifakara Health InstituteCentre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of OxfordInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteInterventions and Clinical Trials Department, Ifakara Health InstituteLaboratory of Malaria and Vector ResearchCentre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of OxfordCentre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford
医学研究方法预防医学基础医学
Minassian Angela M.,Milando Florence,Silk Sarah E.,Mtaka Ivanny M.,Mpina Maximillian,Simon Beatus,Athumani Thabit,Mswata Sarah,Wang Lawrence T.,Rashid Mohammed,Lweno Omary,Cho Jee-Sun,Nyaulingo Gloria,Long Carole A.,Nugent Fay L.,Ahmed Saumu,Mohammed Latipha,Nielsen Carolyn M.,Draper Simon J.,Lilolime Nasoro S.,Hodgson Susanne H.,King Lloyd D. W.,Barrett Jordan R.,Diouf Ababacar,Ali Ali M.,Payne Ruth O.,Olotu Ally I.,Mwamlima Tunu G.,Kalinga Wilmina F.,Mkwepu Fatuma,Mwalimu Bakari,Miura Kazutoyo,Themistocleous Yrene,Lawrie Alison M..Superior antibody immunogenicity of a RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults[EB/OL].(2025-03-28)[2025-05-17].https://www.medrxiv.org/content/10.1101/2023.04.17.23288686.点此复制
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