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

• 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
• Journal Title: BIOENGINEERING & TRANSLATIONAL MEDICINE
• Volume: Volume 8, Number 4
• Publisher: WILEY | 2023-03-28, Pages e10514-e10514
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1002/btm2.10514
• Subjects: Biology, Microbiology; Engineering, Biomedical; Engineering, Chemical; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Technology; Biotechnology & Applied Microbiology; Engineering, Biomedical; Pharmacology & Pharmacy; Engineering; circumsporozoite; junctional epitope; malaria; Plasmodium falciparum; vaccine; B-CELL EPITOPES; T-CELL; SPOROZOITE ATTACHMENT; REPETITIVE EPITOPE; HEPARAN-SULFATE; IMMUNOGENICITY; ADJUVANT; BINDING; MAP; EFFICACY

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.