A stabilized MERS-CoV spike ferritin nanoparticle vaccine elicits robust and protective neutralizing antibody responses
- Abigail E. Powell
- Hannah Caruso
- Soyoon Park
- Jui-Lin Chen
- Jessica O’Rear
- Brian J. Ferrer
- Daniel J. Stieh
- Adam M. Weiss
- David M. Belnap
- Audrey Walker
- Anneliese Bruening
- Airn Hartwig
- Kaitlin R. Sprouse
- Amin Addetia
- Abeer N. Alshukairi
- Vida Ahyong
- Cristy S. Dougherty
- David Veesler
- Richard Bowen
- Julie E. Ledgerwood
- Michael S. Kay
- Payton A.-B. Weidenbacher
- Brad A. Palanski
2026-02-05
Middle East respiratory syndrome coronavirus (MERS-CoV) was identified as a human pathogen in 2012 and causes ongoing sporadic infections and outbreak clusters. Despite case fatality rates (CFRs) of over 30% and considerable pandemic potential, a safe and efficacious vaccine has not been developed. Here we report the design, characterization, and preclinical evaluation of MERS-CoV antigens. Our lead candidate comprises a stabilized spike displayed on a self-assembling ferritin nanoparticle that can be produced from a high-expressing, stable cell pool. This vaccine elicits robust MERS-CoV pseudovirus and authentic virus neutralizing antibody titers in BALB/c mice. Immunization of male non-human primates (NHPs) with one dose of Alhydrogel-adjuvanted vaccine elicited a > 10 3 geometric mean titer of pseudovirus neutralizing antibodies that was boosted with a second dose. Sera from these NHPs exhibited cross-reactivity against spike-pseudotyped lentiviruses from MERS-CoV clades A, B, and C as well as a distant pangolin merbecovirus. In human DPP4 transgenic mice, immunization provided dose-dependent protection against MERS-CoV lethal challenge, and in an established alpaca challenge model using female alpacas, immunization fully protected against MERS-CoV infection. This MERS-CoV nanoparticle vaccine is a promising candidate for clinical advancement to protect at-risk individuals and for future use in a potential outbreak setting.