Controlled human malaria infection to evaluate the efficacy of the asexual blood-stage malaria vaccine candidate GMZ2- CAF01

DSpace Repositorium (Manakin basiert)


Dateien:

Zitierfähiger Link (URI): http://hdl.handle.net/10900/153331
http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-1533316
http://dx.doi.org/10.15496/publikation-94670
Dokumentart: Dissertation
Erscheinungsdatum: 2024-05-14
Sprache: Englisch
Fakultät: 4 Medizinische Fakultät
Fachbereich: Medizin
Gutachter: Kremsner, Peter (Prof. Dr.)
Tag der mündl. Prüfung: 2023-07-04
DDC-Klassifikation: 610 - Medizin, Gesundheit
Lizenz: http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de
Zur Langanzeige

Abstract:

Malaria is a life-threatening protozoan parasite disease transmitted by mosquitoes, which infected approximately 228 million people worldwide in 2018, of which 405,000 people died. Even with existing control methods, such as mosquito nets and insecticides, as well as various therapies, resistances to these methods are increasing as well. It would, therefore, be desirable if a vaccine against this dis- ease were developed to tackle this problem sustainably. So far, there is only one vaccine that has been positively evaluated by scientists and is being tested in larger implementation studies in Africa, called RTS,S. Nevertheless, the e↵ective- ness of this pre-erythrocytic vaccine is not yet satisfactory, which is why research continues to be carried out on various alternatives. One of these projects is the blood-stage vaccine candidate Recombinant Lactococcus lactis Hybrid GLURP and MSP3 (GMZ2), which was tested in this study. Previous studies in both animals and humans showed that this candidate proved to be well-tolerated and produced a convincing antibody profile. Since these studies used aluminum hydroxide as the adjuvant, a further boost was expected by using the novel Cationic Adjuvant Formulation 01 (CAF01), which could further increase the immunity and, ulti- mately, the e↵ectiveness. GMZ2CAF01 tries to induce the semi-immunity that occurs in people who permanently live in endemic malaria regions, thereby con- trolling the multiplication of the pathogen in the blood. Based on a Controlled Human Malaria Infection (CHMI), this study tried to test the e cacy of the vac- cine candidate GMZ2CAF01, as well as to make a statement about the safety of the methodology of the CHMI. 50 healthy Gabonese male participants with life- long exposure to malaria were randomly placed into five groups: Group A received a rabies vaccine as placebo, Group B received 100 μg GMZ2-Alhydrogel, Group C received 30 μg GMZ2-CAF01, and Group D and E received 100 μg GMZ2-CAF01. All but Group E received subsequent CHMI via direct venous inoculation (DVI) with 3,200 P. falciparum sporozoites (PfSPZ). This methodology was previously developed at the Institute of Tropical Medicine, University of Tu ̈bingen, to guaran- tee a 100% infection with malaria. Subsequently, the subjects were questioned and observed for any adverse event (AE)s of the CHMI, and regular blood tests were carried out to determine parasitemia through microscopy, which was confirmed by means of Polymerase Chain Reaction (PCR). As soon as either a parasitemia of over 1,000 or a lower parasitemia accompanied by malaria symptoms was de- tected, the volunteers were treated with artemether-lumefantrine. The remaining participants were treated with artemether-lumefantrine after day 35 post CHMI. It could be confirmed that CHMI proved to be safe and that there were no serious adverse events (SAE)s that occurred. However, almost all subjects experienced at least one AE, of which Grade 1 headache was the most common AE. There was no significant di↵erence between the groups in terms of both the occurrence of malaria and the time until malaria occurred. In conclusion, it can be said that the GMZ2CAF01 vaccine candidate did not induce the semi-immunity that was desired. However, CHMI proved to be a safe and promising method for studying malaria immunization and therapies.

Das Dokument erscheint in: