Sustained exposure to multivalent antigen-decorated nanoparticles generates broad anti-coronavirus responses

Abstract

The threat of future coronavirus pandemics requires developing effective vaccine technologies that provide broad and long-lasting protection against circulating and emerging strains. Here, we report a multivalent liposomal hydrogel depot vaccine technology comprising the receptor binding domain (RBD) of up to four relevant coronavirus strains from severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) non-covalently displayed on the surface of the liposomes within the hydrogel structure. The multivalent presentation and sustained exposure of RBD antigens improved the potency, neutralizing activity, durability, and consistency of antibody responses across homologous and heterologous coronavirus strains in a naive murine model. When administrated in animals pre-exposed to wild-type SARS-CoV-2 antigens, liposomal hydrogels elicited durable antibody responses against the homologous SARS and MERS strains for more than 6 months and elicited neutralizing activity against the immune-evasive SARS-CoV-2 variant Omicron BA.4/BA.5. Overall, the tunable liposomal hydrogel platform we report here generates robust responses against diverse coronaviruses, supporting global efforts to respond to future viral outbreaks.