دورية أكاديمية
A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection.
| العنوان: | A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection. |
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| المؤلفون: | Murphy SC; Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA.; Department of Microbiology, University of Washington, Seattle, WA 98109, USA., Vaughan AM; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA., Kublin JG; Department of Global Health, University of Washington, Seattle, WA 98195, USA.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA., Fishbauger M; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Seilie AM; Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA., Cruz KP; Department of Laboratory Medicine and Pathology and Center for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, WA 98109, USA., Mankowski T; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Firat M; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Magee S; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Betz W; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Kain H; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Camargo N; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Haile MT; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Armstrong J; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Fritzen E; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Hertoghs N; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Kumar S; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Sather DN; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA., Pinder LF; Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98195, USA., Deye GA; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health , Bethesda, MD, USA., Galbiati S; Emmes Company, Rockville, MD, USA., Geber C; Emmes Company, Rockville, MD, USA., Butts J; Emmes Company, Rockville, MD, USA., Jackson LA; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA., Kappe SHI; Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA 98109, USA.; Department of Pediatrics, University of Washington, Seattle, WA 98105, USA.; Department of Global Health, University of Washington, Seattle, WA 98195, USA. |
| المصدر: | Science translational medicine [Sci Transl Med] 2022 Aug 24; Vol. 14 (659), pp. eabn9709. Date of Electronic Publication: 2022 Aug 24. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101505086 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1946-6242 (Electronic) Linking ISSN: 19466234 NLM ISO Abbreviation: Sci Transl Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Association for the Advancement of Science |
| مواضيع طبية MeSH: | Insect Bites and Stings*/chemically induced , Malaria*/prevention & control , Malaria Vaccines* , Malaria, Falciparum*/parasitology , Malaria, Falciparum*/prevention & control , Parasites*, Animals ; Humans ; Plasmodium falciparum/genetics ; Sporozoites/genetics ; Vaccines, Attenuated |
| مستخلص: | Genetically engineered live Plasmodium falciparum sporozoites constitute a potential platform for creating consistently attenuated, genetically defined, whole-parasite vaccines against malaria through targeted gene deletions. Such genetically attenuated parasites (GAPs) do not require attenuation by irradiation or concomitant drug treatment. We previously developed a P. falciparum (Pf) GAP with deletions in P52 , P36 , and SAP1 genes (PfGAP3KO) and demonstrated its safety and immunogenicity in humans. Here, we further assessed safety, tolerability, and immunogenicity of the PfGAP3KO vaccine and tested its efficacy against controlled human malaria infection (CHMI) in malaria-naïve subjects. The vaccine was delivered by three ( n = 6) or five ( n = 8) immunizations with ~200 PfGAP3KO-infected mosquito bites per immunization. PfGAP3KO was safe and well tolerated with no breakthrough P. falciparum blood stage infections. Vaccine-related adverse events were predominately localized urticaria related to the numerous mosquito bites administered per vaccination. CHMI via bites with mosquitoes carrying fully infectious Pf NF54 parasites was carried out 1 month after the last immunization. Half of the study participants who received either three or five PfGAP3KO immunizations remained P. falciparum blood stage negative, as shown by a lack of detection of Plasmodium 18 S rRNA in the blood for 28 days after CHMI. Six protected study participants received a second CHMI 6 months later, and one remained completely protected. Thus, the PfGAP3KO vaccine was safe and immunogenic and was capable of inducing protection against sporozoite infection. These results warrant further evaluation of PfGAP3KO vaccine efficacy in dose-range finding trials with an injectable formulation. |
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| معلومات مُعتمدة: | HHSN272201300019C United States AI NIAID NIH HHS; HHSN272201300019I United States AI NIAID NIH HHS |
| المشرفين على المادة: | 0 (Malaria Vaccines) 0 (Vaccines, Attenuated) |
| تواريخ الأحداث: | Date Created: 20220824 Date Completed: 20220826 Latest Revision: 20230928 |
| رمز التحديث: | 20230928 |
| مُعرف محوري في PubMed: | PMC10423335 |
| DOI: | 10.1126/scitranslmed.abn9709 |
| PMID: | 36001680 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1946-6242 |
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| DOI: | 10.1126/scitranslmed.abn9709 |