Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults
| العنوان: | Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults |
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| المؤلفون: | Maximillian Mpina, Natasha Kc, Stephen L. Hoffman, Thomas L. Richie, Robert A. Seder, Elizabeth Saverino, Bakari M Bakari, Fabian Studer, Peter F. Billingsley, Anneth-Mwasi Tumbo, Sumana Chakravarty, Marcel Tanner, Eric R. James, Kamaka R Kassim, Munira Qassim, Claudia Daubenberger, Salim Abdulla, L. W. Preston Church, Omar Juma, Linda Gondwe, Phillip A. Swanson, David Styers, Tobias Schindler, Adam Ruben, Glenda Cosi, Ali Mtoro, Said Jongo, Martina Fink, Yonas Abebe, Beatus Simon, B. Kim Lee Sim, Florence A. Milando |
| المصدر: | Clin Infect Dis |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Plasmodium falciparum, 030231 tropical medicine, Parasitemia, Mali, Tanzania, Gastroenterology, Double blind, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Malaria Vaccines, parasitic diseases, medicine, Animals, Humans, Malaria, Falciparum, biology, business.industry, Vaccine efficacy, medicine.disease, biology.organism_classification, PfSPZ vaccine, Malaria, Europe, Major Articles and Commentaries, 030104 developmental biology, Infectious Diseases, Sporozoites, business |
| الوصف: | Background A vaccine would be an ideal tool for reducing malaria’s impact. PfSPZ Vaccine (radiation attenuated, aseptic, purified, cryopreserved Plasmodium falciparum [Pf] sporozoites [SPZ]) has been well tolerated and safe in >1526 malaria-naive and experienced 6-month to 65-year-olds in the United States, Europe, and Africa. When vaccine efficacy (VE) of 5 doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine was assessed in adults against controlled human malaria infection (CHMI) in the United States and Tanzania and intense field transmission of heterogeneous Pf in Mali, Tanzanians had the lowest VE (20%). Methods To increase VE in Tanzania, we increased PfSPZ/dose (9 × 105 or 1.8 × 106) and decreased numbers of doses to 3 at 8-week intervals in a double blind, placebo-controlled trial. Results All 22 CHMIs in controls resulted in parasitemia by quantitative polymerase chain reaction. For the 9 × 105 PfSPZ group, VE was 100% (5/5) at 3 or 11 weeks (P < .000l, Barnard test, 2-tailed). For 1.8 × 106 PfSPZ, VE was 33% (2/6) at 7.5 weeks (P = .028). VE of dosage groups (100% vs 33%) was significantly different (P = .022). Volunteers underwent repeat CHMI at 37–40 weeks after last dose. 6/6 and 5/6 volunteers developed parasitemia, but time to first parasitemia was significantly longer than controls in the 9 × 105 PfSPZ group (10.89 vs 7.80 days) (P = .039), indicating a significant reduction in parasites in the liver. Antibody and T-cell responses were higher in the 1.8 × 106 PfSPZ group. Conclusions In Tanzania, increasing the dose from 2.7 × 105 to 9 × 105 PfSPZ increased VE from 20% to 100%, but increasing to 1.8 × 106 PfSPZ significantly reduced VE. Clinical Trials Registration NCT02613520. |
| تدمد: | 1537-6591 1058-4838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3950b417e35a43255743108fcdf3410d https://doi.org/10.1093/cid/ciz1152 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3950b417e35a43255743108fcdf3410d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376591 10584838 |
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