We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
A double-blind, placebo-controlled phase 1/2a trial of the genetically attenuated malaria vaccine PfSPZ-GA1.
- Authors
Roestenberg, Meta; Walk, Jona; van der Boor, Saskia C.; Langenberg, Marijke C. C.; Hoogerwerf, Marie-Astrid; Janse, Jacqueline J.; Manurung, Mikhael; Yap, X. Zen; García, Amanda Fabra; Koopman, Jan Pieter R.; Meij, Pauline; Wessels, Els; Teelen, Karina; van Waardenburg, Youri M.; van de Vegte-Bolmer, Marga; van Gemert, Geert Jan; Visser, Leo G.; van der Ven, André J. A. M.; de Mast, Quirijn; Natasha, K. C.
- Abstract
GMOs for good: Despite decades of progress and a multitude of approaches, a durable malaria vaccine remains elusive. Two new clinical studies in this issue report initial testing of genetically engineered malaria vaccines in malaria-naïve adults. Roestenberg et al. studied PfSPZ-GA1, a Plasmodium falciparum SPZ vaccine attenuated by deletion of b9 and slarp. Reuling et al. examined PbVac, SPZ of the rodent-specific parasite P. berghei modified to express the circumsporozoite protein from P. falciparum. Both vaccines were well tolerated and immunogenic. Controlled malaria challenge also indicated some evidence of protection. These genetically engineered vaccines are part of the new wave of malaria vaccines and warrant further clinical testing. Immunization with attenuated Plasmodium sporozoites can induce protection against malaria infection, as shown by Plasmodium falciparum (Pf) sporozoites attenuated by radiation in multiple clinical trials. As alternative attenuation strategy with a more homogeneous population of Pf sporozoites (PfSPZ), genetically engineered Plasmodium berghei sporozoites (SPZ) lacking the genes b9 and slarp induced sterile protection against malaria in mice. Consequently, PfSPZ-GA1 Vaccine, a Pf identical double knockout (Pf∆b9∆slarp), was generated as a genetically attenuated malaria parasite vaccine and tested for safety, immunogenicity, and preliminary efficacy in malaria-naïve Dutch volunteers. Dose-escalation immunizations up to 9.0 × 105 PfSPZ of PfSPZ-GA1 Vaccine were well tolerated without breakthrough blood-stage infection. Subsequently, groups of volunteers were immunized three times by direct venous inoculation with cryopreserved PfSPZ-GA1 Vaccine (9.0 × 105 or 4.5 × 105 PfSPZ, N = 13 each), PfSPZ Vaccine (radiation-attenuated PfSPZ, 4.5 × 105 PfSPZ, N = 13), or normal saline placebo at 8-week intervals, followed by exposure to mosquito bite controlled human malaria infection (CHMI). After CHMI, 3 of 25 volunteers from both PfSPZ-GA1 groups were sterilely protected, and the remaining 17 of 22 showed a patency ≥9 days (median patency in controls, 7 days; range, 7 to 9). All volunteers in the PfSPZ Vaccine control group developed parasitemia (median patency, 9 days; range, 7 to 12). Immunized groups exhibited a significant, dose-related increase in anti-Pf circumsporozoite protein (CSP) antibodies and Pf-specific interferon-γ (IFN-γ)–producing T cells. Although no definite conclusion can be drawn on the potential strength of protective efficacy of PfSPZ-GA1 Vaccine, the favorable safety profile and induced immune responses by PfSPZ-GA1 Vaccine warrant further clinical evaluation.
- Subjects
MALARIA vaccines; VACCINE safety; PLASMODIUM berghei; CIRCUMSPOROZOITE protein; PLASMODIUM falciparum; MALARIA; INTERLEUKIN-22
- Publication
Science Translational Medicine, 2020, Vol 12, Issue 544, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.aaz5629