Powell, A. E.; Caruso, H.; Park, S.; Chen, J.-L.; O'Rear, J.; Ferrer, B. J.; Walker, A.; Bruenig, A.; Hartwig, A.; Ahyong, V.; Dougherty, C. S.; Bowen, R. A.; Ledgerwood, J. E.; Kay, M. S.; Weidenbacher, P. A.- B.; Palanski, B. A.

Middle East respiratory syndrome coronavirus (MERS-CoV) was first identified as a human pathogenic virus in 2012 and is causing ongoing sporadic infections as well as outbreak clusters. Despite case fatality rates (CFRs) of over 30% and the pandemic potential associated with betacoronaviruses, a safe and efficacious vaccine has not been developed for prevention of MERS in at-risk individuals. Here we report the design, in vitro characterization, and preclinical evaluation of MERS-CoV antigens. Our lead candidate comprises a stabilized spike ectodomain displayed on a self-assembling ferritin nanoparticle that can be produced from a high-expressing, stable cell pool. This vaccine elicits robust antibody titers in BALB/c mice as measured by MERS-CoV pseudovirus and live-virus neutralization assays. Immunization of non-human primates (NHPs) with a single dose of Alhydrogel-adjuvanted vaccine elicits >103 geometric mean titer (GMT) of pseudovirus neutralizing antibodies that can be boosted with a second dose. These antibody levels are durable, with GMTs that surpass the post-prime levels for more than 5 months post-boost. Importantly, sera from these NHPs exhibits broad cross-reactivity against lentiviruses pseudotyped with spike proteins from MERS-CoV clades A, B, and C as well as a more distant pangolin merbecovirus. In an established alpaca challenge model, immunization fully protects against viral infection. This protein-based MERS-CoV nanoparticle vaccine is a promising candidate for advancement to clinical development to protect at-risk individuals and for future use in a potential outbreak setting.