A multivalent Plasmodium falciparum circumsporozoite protein-based nanoparticle malaria vaccine elicits a robust and durable antibody response against the junctional epitope and the major repeats

• Type of Material: Article
• Authors: Geetanjali Pendyala, Georgia Institute of Technology; J. Mauricio Calvo-Calle, University of Massachusetts; Alberto Moreno, Emory University; Ravi S Kane, Georgia Institute of Technology
• Language: English
• Date: 2023-03-28
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Authors. Bioengineering & Translational Medicine
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1002/btm2.10514
• Title of Journal or Parent Work: BIOENGINEERING & TRANSLATIONAL MEDICINE
• Volume: 8
• Issue: 4
• Start Page: e10514
• End Page: e10514
• Keywords: vaccine; MAP; Plasmodium falciparum; malaria; REPETITIVE EPITOPE; IMMUNOGENICITY; BINDING; Pharmacology & Pharmacy; B-CELL EPITOPES; circumsporozoite; SPOROZOITE ATTACHMENT; Engineering; junctional epitope; Life Sciences & Biomedicine; ADJUVANT; Technology; EFFICACY; Biotechnology & Applied Microbiology; HEPARAN-SULFATE; T-CELL; Engineering, Biomedical; Science & Technology
• Research Categories: Engineering, Biomedical; Health Sciences, Pathology; Biology, Microbiology; Engineering, Chemical

Abstract

Plasmodium falciparum (Pf) malaria continues to cause considerable morbidity and mortality worldwide. The circumsporozoite protein (CSP) is a particularly attractive candidate for designing vaccines that target sporozoites—the first vertebrate stage in a malaria infection. Current PfCSP-based vaccines, however, do not include epitopes that have recently been shown to be the target of potent neutralizing antibodies. We report the design of a SpyCatcher-mi3-nanoparticle-based vaccine presenting multiple copies of a chimeric PfCSP (cPfCSP) antigen that incorporates these important “T1/junctional” epitopes as well as a reduced number of (NANP)n repeats. cPfCSP-SpyCatcher-mi3 was immunogenic in mice eliciting high and durable IgG antibody levels as well as a balanced antibody response against the T1/junctional region and the (NANP)n repeats. Notably, the antibody concentration elicited by immunization was significantly greater than the reported protective threshold defined in a murine challenge model. Refocusing the immune response toward functionally relevant subdominant epitopes to induce a more balanced and durable immune response may enable the design of a more effective second generation PfCSP-based vaccine.