دورية أكاديمية
Malaria transmission-blocking vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in healthy Malian adults; a phase 1, randomised, controlled trial.
| العنوان: | Malaria transmission-blocking vaccines Pfs230D1-EPA and Pfs25-EPA in Alhydrogel in healthy Malian adults; a phase 1, randomised, controlled trial. |
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| المؤلفون: | Sagara I; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Healy SA; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Assadou MH; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Kone M; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Swihart BJ; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Kwan JL; Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Fintzi J; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Sissoko K; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Kamate B; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Samake Y; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Guindo MA; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Doucoure M; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Niaré K; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Dolo A; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Diarra B; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Rausch KM; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Narum DL; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Jones DS; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., MacDonald NJ; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Zhu D; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Gorres JP; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Imeru A; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Mohan R; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Thera I; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Zaidi I; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Salazar-Miralles F; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Duan J; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Neal J; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Morrison RD; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Muratova O; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Sylla D; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., O'Connell EM; Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Wu Y; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Hume JCC; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Coulibaly MB; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Anderson CF; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA., Traore SF; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Doumbo OK; Malaria Research and Training Center, Mali- National Institute of Allergy and Infectious Diseases International Center for Excellence in Research, University of Sciences, Techniques and Technologies of Bamako, Mali., Duffy PE; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, USA. Electronic address: patrick.duffy@nih.gov. |
| المصدر: | The Lancet. Infectious diseases [Lancet Infect Dis] 2023 Nov; Vol. 23 (11), pp. 1266-1279. Date of Electronic Publication: 2023 Jul 24. |
| نوع المنشور: | Randomized Controlled Trial; Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Intramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 101130150 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-4457 (Electronic) Linking ISSN: 14733099 NLM ISO Abbreviation: Lancet Infect Dis Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001- |
| مواضيع طبية MeSH: | Malaria, Falciparum* , Malaria Vaccines*/adverse effects , Meningococcal Vaccines*, Animals ; Adult ; Humans ; Adolescent ; Young Adult ; Middle Aged ; Aluminum Hydroxide ; Plasmodium falciparum ; Double-Blind Method ; Immunogenicity, Vaccine |
| مستخلص: | Background: Malaria transmission-blocking vaccines target mosquito-stage parasites and will support elimination programmes. Gamete vaccine Pfs230D1-EPA/Alhydrogel induced superior activity to zygote vaccine Pfs25-EPA/Alhydrogel in malaria-naive US adults. Here, we compared these vaccines in malaria-experienced Malians. Methods: We did a pilot safety study then double-blind, block-randomised, comparator-controlled main-phase trial in malaria-intense Bancoumana, Mali. 18-50-year-old healthy non-pregnant, non-breastfeeding consenting adult residents were randomly assigned (1:1:1:1) to receive four doses at months 0, 1, 4·5, and 16·5 of either 47 μg Pfs25, 40 μg Pfs230D1 or comparator (Twinrix or Menactra)-all co-administered with normal saline for blinding-or 47 μg Pfs25 plus 40 μg Pfs230D1 co-administered. We documented safety and tolerability (primary endpoint in the as-treated populations) and immunogenicity (secondary endpoint in the as-treated populations: ELISA, standard-membrane-feeding assay, and mosquito direct skin feed assay). This trial is registered at ClinicalTrials.gov, NCT02334462. Findings: Between March 19, and June 2, 2015, we screened 471 individuals. Of 225 enrolled for the pilot and main cohorts, we randomly assigned 25 participants to pilot safety cohort groups of five (20%) to receive a two-dose series of Pfs25-EPA/Alhydrogel (16 μg), Pfs230D1-EPA/Alhydrogel (15 μg) or comparator, followed by Pfs25-EPA/Alhydrogel (16 μg) plus Pfs230D1-EPA/Alhydrogel (15 μg) or comparator plus saline. For the main cohort, we enrolled 200 participants between May 11 and June 2, 2015, to receive a four-dose series of 47 μg Pfs25-EPA/Alhydrogel plus saline (n=50 [25%]; Pfs25), 40 μg Pfs230D1-EPA/Alhydrogel plus saline (n=49 [25%]; Pfs230D1), 47 μg Pfs25-EPA/Alhydrogel plus 40 μg Pfs230D1-EPA/Alhydrogel (n=50 [25%]; Pfs25 plus Pfs230D1), or comparator (Twinrix or Menactra) plus saline (n=51 [25%]). Vaccinations were well tolerated in the pilot safety and main phases. Most vaccinees became seropositive after two Pfs230D1 or three Pfs25 doses; peak titres increased with each dose thereafter (Pfs230D1 geometric mean: 77·8 [95% CI 56·9-106·3], 146·4 [108·3-198·0], and 410·2 [301·6-558·0]; Pfs25 geometric mean 177·7 [130·3-242·4] and 315·7 [209·9-474·6]). Functional activity (mean peak transmission-reducing activity) appeared for Pfs230D1 (74·5% [66·6-82·5]) and Pfs25 plus Pfs230D1 (68·6% [57·3-79·8]), after the third dose and after the fourth dose (88·9% [81·7-96·2] for Pfs230D1 and 85·0% [78·4-91·5] Pfs25 plus Pfs230D1) but not for Pfs25 (58·2% [49·1-67·3] after the third dose and 58·2% [48·5-67·9] after the fourth dose). Pfs230D1 transmission-reducing activity (73·7% [64·1-83·3]) persisted 10 weeks after the fourth dose. Transmission-reducing activity of 80% was estimated at 1659 ELISA units for Pfs25, 218 for Pfs230D1, and 223 for Pfs230D1 plus Pfs25. After 3850 direct skin feed assays, 35 participants (12 Pfs25, eight Pfs230D1, five Pfs25 plus Pfs230D1, and ten comparator) had transmitted parasites at least once. The proportion of positive assays in vaccine groups (Pfs25 33 [3%] of 982 [-0·013 to 0·014], Pfs230D1 22 [2%] of 954 [-0·005 to 0·027], and combination 11 [1%] of 940 [-0·024 to 0·002]) did not differ from that of the comparator (22 [2%] of 974), nor did Pfs230D1 and combination groups differ (-0·024 to 0·001). Interpretation: Pfs230D1 but not Pfs25 vaccine induces durable serum functional activity in Malian adults. Direct skin feed assays detect parasite transmission to mosquitoes but increased event rates are needed to assess vaccine effectiveness. Funding: Intramural Research Program of the National Institute of Allergy and Infectious Diseases and US National Institutes of Health. Competing Interests: Declaration of interests We declare no competing interests. (Copyright © 2023 Elsevier Ltd. All rights reserved.) |
| التعليقات: | Comment in: Lancet Infect Dis. 2023 Nov;23(11):1210-1212. (PMID: 37499677) |
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| معلومات مُعتمدة: | ZIA AI001009 United States ImNIH Intramural NIH HHS; ZIA AI001010 United States ImNIH Intramural NIH HHS; ZIA AI001056 United States ImNIH Intramural NIH HHS; ZIA AI001177 United States ImNIH Intramural NIH HHS |
| سلسلة جزيئية: | ClinicalTrials.gov NCT02334462 |
| المشرفين على المادة: | 5QB0T2IUN0 (Aluminum Hydroxide) 0 (Malaria Vaccines) 0 (Meningococcal Vaccines) |
| تواريخ الأحداث: | Date Created: 20230727 Date Completed: 20231030 Latest Revision: 20231112 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC10615700 |
| DOI: | 10.1016/S1473-3099(23)00276-1 |
| PMID: | 37499679 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1474-4457 |
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| DOI: | 10.1016/S1473-3099(23)00276-1 |