Screening of viral-vectored P. falciparum pre-erythrocytic candidate vaccine antigens using chimeric rodent parasites.

Autor: Kolli SK; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Salman AM; Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom., Ramesar J; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Chevalley-Maurel S; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Kroeze H; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Geurten FGA; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Miyazaki S; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Mukhopadhyay E; Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom., Marin-Mogollon C; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Franke-Fayard B; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands., Hill AVS; Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom., Janse CJ; Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Jul 12; Vol. 16 (7), pp. e0254498. Date of Electronic Publication: 2021 Jul 12 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0254498
Abstrakt: To screen for additional vaccine candidate antigens of Plasmodium pre-erythrocytic stages, fourteen P. falciparum proteins were selected based on expression in sporozoites or their role in establishment of hepatocyte infection. For preclinical evaluation of immunogenicity of these proteins in mice, chimeric P. berghei sporozoites were created that express the P. falciparum proteins in sporozoites as an additional copy gene under control of the uis4 gene promoter. All fourteen chimeric parasites produced sporozoites but sporozoites of eight lines failed to establish a liver infection, indicating a negative impact of these P. falciparum proteins on sporozoite infectivity. Immunogenicity of the other six proteins (SPELD, ETRAMP10.3, SIAP2, SPATR, HT, RPL3) was analyzed by immunization of inbred BALB/c and outbred CD-1 mice with viral-vectored (ChAd63 or ChAdOx1, MVA) vaccines, followed by challenge with chimeric sporozoites. Protective immunogenicity was determined by analyzing parasite liver load and prepatent period of blood stage infection after challenge. Of the six proteins only SPELD immunized mice showed partial protection. We discuss both the low protective immunogenicity of these proteins in the chimeric rodent malaria challenge model and the negative effect on P. berghei sporozoite infectivity of several P. falciparum proteins expressed in the chimeric sporozoites.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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