Strategic variants of CSP delivered as SynDNA vaccines demonstrate heterogeneity of immunogenicity and protection from plasmodium infection in a murine model

Sophia M. Reeder, Mamadou A. Bah, Nicholas J. Tursi, Rebekah C. Brooks, Ami Patel, Rianne Esquivel, Alison Eaton, Hugo Jhun, Jacqueline Chu, Kevin Kim, Ziyang Xu, Fidel Zavala, David B. Weiner

Research output: Contribution to journalArticlepeer-review

Abstract

Malaria infects millions of people every year, and despite recent advances in controlling disease spread, such as vaccination, it remains a global health concern. The circumsporozoite protein (CSP) has long been acknowledged as a key target in antimalarial immunity. Leveraging the DNA vaccine platform against this formidable pathogen, the following five synthetic DNA vaccines encoding variations of CSP were designed and studied: 3D7, GPI1, DGPI, TM, and DD2. Among the single CSP antigen constructs, a range of immunogenicity was observed with DGPI generating the most robust immunity. In an intravenous (i.v.) sporozoite challenge, the best protection among vaccinated mice was achieved by DGPI, which performed almost as well as the monoclonal antibody 311 (MAb 311) antibody control. Further analyses revealed that DGPI develops high-molecular-weight multimers in addition to monomeric CSP. We then compared the immunity generated by DGPI versus synDNA mimics for the antimalaria vaccines RTS,S and R21. The anti-CSP antibody responses induced were similar among these three immunogens. T cell responses demonstrated that DGPI induced a more focused anti-CSP response. In an infectious mosquito challenge, all three of these constructs generated inhibition of liver-stage infection as well as immunity from blood-stage parasitemia. This study demonstrates that synDNA mimics of complex malaria immunogens can provide substantial protection as can a novel synDNA vaccine DGPI.

Original languageEnglish (US)
Article numbere00728-20
JournalInfection and immunity
Volume89
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • DNA vaccines
  • Immunization
  • Malaria

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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