@article{eb618e76713945e09271795153ed3018,
title = "Strategic variants of CSP delivered as SynDNA vaccines demonstrate heterogeneity of immunogenicity and protection from plasmodium infection in a murine model",
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.",
keywords = "DNA vaccines, Immunization, Malaria",
author = "Reeder, {Sophia M.} and Bah, {Mamadou A.} and Tursi, {Nicholas J.} and Brooks, {Rebekah C.} and Ami Patel and Rianne Esquivel and Alison Eaton and Hugo Jhun and Jacqueline Chu and Kevin Kim and Ziyang Xu and Fidel Zavala and Weiner, {David B.}",
note = "Funding Information: This research was supported by Bill and Melinda Gates Foundation grant 6789101374. H.J., A.E., and F.Z. thank the Bloomberg Philanthropies and the Bill and Melinda Gates Foundation for continued support. Funding Information: S.M.R. is supported by a University of Pennsylvania training grant (2-T32-CA-115299-11 RE). D.B.W. is supported by the W. W. Smith Charitable Trust Professorship in Cancer Research. A.P. is supported by the Caspar Wistar Fellows Program. D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board series. In the interest of disclosure, D.B.W. reports the following paid associations with commercial partners: GeneOne (Consultant), Geneos (Advisory Board), Astrazeneca (Speaker), Inovio (BOD, SRA, Stock), Sanofi (Advisory Board), BBI (Advisory Board), and Pfizer (Speaker). Funding Information: We thank the Animal Facility staff at the Wistar Institute for providing care to the animals. We also thank the Flow Cytometry Core at Wistar and the Electron Microscopy Core at the University of Pennsylvania for valuable experimental support. This research was supported by Bill and Melinda Gates Foundation grant 6789101374. H.J., A.E., and F.Z. thank the Bloomberg Philanthropies and the Bill and Melinda Gates Foundation for continued support. BioRender (Toronto, Canada) was used to create the graphics in Fig. 1 to 3 and Fig. 5 and to compile all figures. R.E., S.M.R., and D.B.W. conceptualized the project; S.M.R., M.A.B., N.J.T., R.C.B., R.E., A.E., H.J., J.C., K.K., and Z.X. performed the experiments; A.P., F.Z., and D.B.W. provided guidance; S.M.R. interpreted results and wrote the manuscript. All authors have read and agreed to the published version of the manuscript. S.M.R. is supported by a University of Pennsylvania training grant (2-T32-CA-115299-11 RE). D.B.W. is supported by the W. W. Smith Charitable Trust Professorship in Cancer Research. A.P. is supported by the Caspar Wistar Fellows Program. D.B.W. has received grant funding, participates in industry collaborations, has received speaking honoraria, and has received fees for consulting, including serving on scientific review committees and board series. In the interest of disclosure, D.B.W. reports the following paid associations with commercial partners: GeneOne (Consultant), Geneos (Advisory Board), Astrazeneca (Speaker), Inovio (BOD, SRA, Stock), Sanofi (Advisory Board), BBI (Advisory Board), and Pfizer (Speaker). Publisher Copyright: Copyright {\textcopyright} 2021 Reeder et al.",
year = "2021",
month = oct,
doi = "10.1128/IAI.00728-20",
language = "English (US)",
volume = "89",
journal = "Infection and immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "10",
}