Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences

Authors

Clifford T. Hayashi, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington DC 20052, USA.
Yi Cao, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington DC 20052, USA.
Fidel Zavala, Johns Hopkins Malaria Research Institute, Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21215, USA.
Hayk Simonyan, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, George Washington University, Washington DC 20052, USA.
Colin N. Young, Department of Pharmacology and Physiology, School of Medicine and Health Sciences, George Washington University, Washington DC 20052, USA.
Nirbhay Kumar, Department of Global Health, Milken Institute School of Public Health, George Washington University, Washington DC 20052, USA. Electronic address: nkumar@gwu.edu.

Document Type

Journal Article

Publication Date

10-10-2023

Journal

Vaccine

DOI

10.1016/j.vaccine.2023.10.009

Keywords

Circumsporozoite protein; Malaria; Plasmodium falciparum; Vaccine

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 and CD8 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.

APA Citation

Hayashi, Clifford T.; Cao, Yi; Zavala, Fidel; Simonyan, Hayk; Young, Colin N.; and Kumar, Nirbhay, "Antibodies elicited by Plasmodium falciparum circumsporozoite proteins lacking sequentially deleted C-terminal amino acids reveal mouse strain and epitopes specific differences" (2023). GW Authored Works. Paper 3618.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3618

Department

Global Health