Merbecovirus S2 subunit vaccines elicit cross reactive antibodies and provide partial protection against MERS coronavirus.

Since the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV), a virus that has caused a high case fatality rate of 36%, other merbecoviruses have been reported to also be capable of infecting human cells. Given the threat of Merbecovirus spillover to humans, we developed virus-like particle vaccines presenting the S2 subunit proteins of MERS-CoV, NeoCoV, HKU4, or HKU25. Mice were vaccinated with the homotypic vaccines, and IgG endpoint titers were measured against S2 proteins of the same panel of viruses, confirming high cross-reactivity across all four viruses. Based on characterization by antigenic cartography, MERS-CoV and HKU4 S2 proteins were selected as optimal components for a cocktail vaccine. MERS-CoV and NeoCoV homotypic vaccines, along with the mixture vaccine, provided partial protection in transgenic mice against a MERS-CoV challenge. These findings could serve as an important step toward designing pan-Merbecovirus vaccines in preparation for future outbreaks.