Journal article icon

Journal article

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

Abstract:

To screen for additional vaccine candidate antigens of Plasmodium pre-erythrocytic stages, fourteen Pfalciparum 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 Pberghei sporozoites were created that express the Pfalciparum 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 Pfalciparum 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 Pberghei sporozoite infectivity of several Pfalciparum proteins expressed in the chimeric sporozoites.

Publication status:
Published
Peer review status:
Peer reviewed

Actions


Access Document


Files:
Publisher copy:
10.1371/journal.pone.0254498

Authors


More by this author
Role:
Author
ORCID:
0000-0001-6125-0036
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Jenner Institute
Role:
Author
ORCID:
0000-0002-9259-7339


Publisher:
Public Library of Science
Journal:
PLoS ONE More from this journal
Volume:
16
Issue:
7
Article number:
e0254498
Publication date:
2021-07-12
Acceptance date:
2021-06-28
DOI:
EISSN:
1932-6203
Pmid:
34252120


Terms of use



Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP