MVI is increasingly reliant on transgenic sporozoite challenge studies performed in the lab of Fidel Zavala (Johns Hopkins School of Public Health). In this model, normal mice with intact immune systems are challenged either intravenously or by mosquito bite with Pb sporozoites, in which the antigen of interest has been replaced by its P. falciparum ortholog, thereby enabling assessment of immune responses to a particular antigen/epitope. In an initial proof-of-concept study, circumsporozoite (CSP) monoclonal antibodies (mAbs) are being passively transferred to mice that are then challenged with transgenic parasites, in which the PbCSP has been replaced in its entirety by PfCSP. The mice are assessed for reduction in parasite liver burden by RT-PCR and for sterile protection. In support of the HPATIC project, a number of transgenic parasites will be generated to assess protective efficacy via passive transfer of monoclonal antibodies against the antigen of interest. In the upcoming years, the lab will perform challenge studies to evaluate these antigens and will continue to generate and characterize new transgenic parasites in support of projects as needed.
Kastenmüller K1, Espinosa DA, Trager L, Stoyanov C, Salazar AM, Pokalwar S, Singh S, Dutta S, Ockenhouse CF, Zavala F, Seder RA. Full-length Plasmodium falciparum circumsporozoite protein administered with long-chain poly(I·C) or the Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion elicits potent antibody and CD4+ T cell immunity and protection in mice. Infect Immun. 2013 Mar;81(3):789-800. doi: 10.1128/IAI.01108-12. Epub 2012 Dec 28.