Immunization with PfGBP130 generates antibodies that inhibit RBC invasion by P. falciparum parasites.

Autor:	Johnson Y; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States., Shakri AR; Department of Internal Medicine, University of South Florida, Tampa, FL, United States., Pond-Tor S; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States.; Center for International Health Research, Rhode Island Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States., Jnawali A; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States.; Center for International Health Research, Rhode Island Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States., Najrana T; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States.; Center for International Health Research, Rhode Island Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States., Wu H; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States.; Center for International Health Research, Rhode Island Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States., Badhai J; Department of Internal Medicine, University of South Florida, Tampa, FL, United States., Alameh MG; Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Weissman D; Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States., Kabyemela E; Department of Pathology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania., Duffy P; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States., Fried M; Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States., Kurtis J; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States.; Center for International Health Research, Rhode Island Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States., Raj DK; Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, United States.; Department of Internal Medicine, University of South Florida, Tampa, FL, United States.; Center for International Health Research, Rhode Island Hospital, Warren Alpert Medical School, Brown University, Providence, RI, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 May 28; Vol. 15, pp. 1350560. Date of Electronic Publication: 2024 May 28 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1350560
Abstrakt:	Background: Despite decades of effort, Plasmodium falciparum malaria remains a leading killer of children. The absence of a highly effective vaccine and the emergence of parasites resistant to both diagnosis as well as treatment hamper effective public health interventions. Methods and Results: To discover new vaccine candidates, we used our whole proteome differential screening method and identified PfGBP130 as a parasite protein uniquely recognized by antibodies from children who had developed resistance to P. falciparum infection but not from those who remained susceptible. We formulated PfGBP130 as lipid encapsulated mRNA, DNA plasmid, and recombinant protein-based immunogens and evaluated the efficacy of murine polyclonal anti-PfGBP130 antisera to inhibit parasite growth in vitro. Immunization of mice with PfGBP130-A (aa 111-374), the region identified in our differential screen, formulated as a DNA plasmid or lipid encapsulated mRNA, but not as a recombinant protein, induced antibodies that inhibited RBC invasion in vitro . mRNA encoding the full ectodomain of PfGBP130 (aa 89-824) also generated parasite growth-inhibitory antibodies. Conclusion: We are currently advancing PfGBP130-A formulated as a lipid-encapsulated mRNA for efficacy evaluation in non-human primates. Competing Interests: Author JK is a scientific co-founder of Ocean Biomedical which seeks to develop malaria vaccines. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Johnson, Shakri, Pond-Tor, Jnawali, Najrana, Wu, Badhai, Alameh, Weissman, Kabyemela, Duffy, Fried, Kurtis and Raj.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu