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Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences.
- Source :
-
Vaccine [Vaccine] 2023 Nov 02; Vol. 41 (46), pp. 6824-6833. Date of Electronic Publication: 2023 Oct 10. - Publication Year :
- 2023
-
Abstract
- Malaria affects ∼ ¼ billion people globally and requires the development of additional tools to aid in elimination efforts. The recently approved RTS,S/AS01 vaccine represents a positive step, however, the moderate efficacy necessitates the development of more efficacious vaccines. PfCSP is a key target antigen for pre-erythrocytic vaccines aimed at preventing Plasmodium falciparum malaria infections. Epitopes within the central repeat region and at the junction of the repeat and N-terminal domain are well documented as major protective B cell epitopes. On the other hand, a majority of antibodies against the epitopes in the C-terminal domain, have been shown to be non-protective against sporozoite challenge. The C-terminal domain, however, contains CD4 <superscript>+</superscript>  and CD8 <superscript>+</superscript>  T cell epitopes previously shown to be important for regulating immune responses. The present study was designed to further explore the immunomodulatory potential of the C-terminal domain using DNA vaccines encoding PfCSP with sequential C-terminal truncations following known T cell epitopes. Five DNA vaccines encoding different truncations of PfCSP within the C-terminal domain were administered via intramuscular route and in vivo electroporation for effective immunogenicity. Protection in mice was evaluated by challenge with transgenic P. berghei expressing PfCSP. In Balb/c mice, antibody responses and protective efficacy were both affected progressively with sequential deletion of C-terminal amino acid residues. Similar studies in C57Bl/6 mice revealed that immunizations with plasmids encoding truncated PfCSP showed partial protection from sporozoite challenge with no significant differences in antibody titers observed compared to full-length PfCSP DNA immunized mice. Further analysis revealed murine strain-specific differences in the recognition of specific epitopes.<br />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.<br /> (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Mice
Female
Epitopes, B-Lymphocyte immunology
Epitopes, B-Lymphocyte genetics
Epitopes immunology
Epitopes genetics
Sporozoites immunology
Protozoan Proteins immunology
Protozoan Proteins genetics
Malaria Vaccines immunology
Malaria Vaccines administration & dosage
Malaria Vaccines genetics
Plasmodium falciparum immunology
Plasmodium falciparum genetics
Antibodies, Protozoan immunology
Vaccines, DNA immunology
Vaccines, DNA genetics
Vaccines, DNA administration & dosage
Epitopes, T-Lymphocyte immunology
Epitopes, T-Lymphocyte genetics
Malaria, Falciparum prevention & control
Malaria, Falciparum immunology
Mice, Inbred BALB C
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 41
- Issue :
- 46
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 37827967
- Full Text :
- https://doi.org/10.1016/j.vaccine.2023.10.009