A Diversity Covering (DiCo) Plasmodium vivax apical membrane antigen-1 vaccine adjuvanted with RFASE/RSL10 yields high levels of growth-inhibitory antibodies.

Autor: Faber BW; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, the Netherlands. Electronic address: Faber@bprc.nl., Yeoh LM; Burnet Institute, Melbourne, Victoria, Australia; Department of Medicine, The University of Melbourne, Victoria, Australia., Kurtovic L; Burnet Institute, Melbourne, Victoria, Australia; Central Clinical School and Department of Microbiology, Monash University, Victoria, Australia., Mol WEM; Immunovo BV Den Bosch, the Netherlands., Poelert M; Symeres, Groningen, the Netherlands., Smits E; Symeres, Groningen, the Netherlands., Rodriguez Garcia R; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, the Netherlands., Mandalawi-Van der Eijk M; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, the Netherlands., van der Werff N; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, the Netherlands., Voorberg-van der Wel A; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, the Netherlands., Remarque EJ; Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands., Beeson JG; Burnet Institute, Melbourne, Victoria, Australia; Central Clinical School and Department of Microbiology, Monash University, Victoria, Australia; Department of Infectious Diseases, University of Melbourne, Victoria, Australia., Kocken CHM; Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2024 Mar 07; Vol. 42 (7), pp. 1785-1792. Date of Electronic Publication: 2024 Feb 16.
DOI: 10.1016/j.vaccine.2024.02.029
Abstrakt: Plasmodium vivax malaria is increasingly recognized as a major global health problem and the socio-economic impact of P.vivax-induced burden is huge. Vaccine development against P. vivax malaria has been hampered by the lack of an in vitro culture system and poor access to P. vivax sporozoites. The recent generation of Plasmodium falciparum parasites that express a functional P. vivax AMA1 molecule has provided a platform for in vitro evaluation of PvAMA1 as a potential blood stage vaccine. Three so-called PvAMA1 Diversity Covering (DiCo) proteins were designed to assess their potential to induce a functional and broad humoral immune response to the polymorphic PvAMA1 molecule. Rabbits were immunized with the mixture of three, Pichia-produced, PvAMA1 DiCo proteins, as well as with 2 naturally occurring PvAMA1 alleles. For these three groups, the experimental adjuvant raffinose fatty acid sulfate ester (RFASE) was used, while in a fourth group the purified main mono-esterified constituent (RSL10) of this adjuvant was used. Animals immunized with the mixture of the three PvAMA1 DiCo proteins in RFASE showed high anti-PvAMA1 antibody titers against three naturally occurring PvAMA1variants while also high growth-inhibitory capacity was observed against P. falciparum parasites expressing PvAMA1. This supports further clinical development of the PvAMA1 DiCo mixture as a potential malaria vaccine. However, as the single allele PvAMA1 SalI-group showed similar characteristics in antibody titer and inhibition levels as the PvAMA1 DiCo mixture-group, this raises the question whether a mixture is really necessary to overcome the polymorphism in the vaccine candidate. RFASE induced strong humoral responses, as did the animals immunized with the purified component, RSL10. This suggests that RSL10 is the active ingredient. However, one of the RSL10-immunized animal showed a delayed response, necessitating further research into the clinical development of RSL10.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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