Novel malaria antigen Plasmodium yoelii E140 induces antibody-mediated sterile protection in mice against malaria challenge.

Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P. yoelii challenge of mice. Vaccines targeting PyE140 reproducibly induced up to 100% sterile protection in both inbred and outbred murine challenge models. Although PyE140 immunization induced high frequency and multifunctional CD8+ T cell responses, as well as CD4+ T cell responses, protection was mediated by PyE140 antibodies acting against blood stage parasites. Protection in mice was long-lasting with up to 100% sterile protection at twelve weeks post-immunization and durable high titer anti-PyE140 antibodies. The E140 antigen is expressed in all Plasmodium species, is highly conserved in both P. falciparum lab-adapted strains and endemic circulating parasites, and is thus a promising lead vaccine candidate for future evaluation against human malaria parasite species.
Competing Interests: The authors have read the journal’s policy and have the following conflicts: ECS, KJL, and JCA are named inventors on a patent application US PCT/US18/25510 covering methods and compositions for vaccinating against malaria. JCA is a named inventor on US patent number 10, 195, 260, US Patent Application No. 16/230,512, and related foreign applications covering the PfE140 antigen. NR, KO, JW, and JCA are/were employed by CAMRIS International, which is a commercial company that owns the rights to the PfE140 antigen under patent number 10, 195, 260. This does not alter our adherence to PLOS ONE policies on sharing data and materials. ERPi Inc., Meso Scale Diagnostics, Sanaria, and General Dynamics Information Technology Inc. are current affiliations for some authors who previously contributed to the study. Neither ERPi Inc., Meso Scale Diagnostics, Sanaria, nor General Dynamics Information Technology Inc. made any contribution to the study.