Effective Mucosal Adjuvantation of the Intranasal Enterovirus A71 Vaccine With Zymosan

ABSTRACT Enterovirus A71 (EV‐A71) has caused hand, foot, and mouth disease with an increased prevalence of neurological complications and acute mortality, threatening young children around the globe. By provoking mucosal immunity, intranasal vaccination has been suggested to prevent EV‐A71 infection. However, antigens delivered via the nasal route usually fail to induce a protective memory response. Zymosan has been identified to activate multiple pattern recognition receptors to orchestrate innate and adaptive immunity. Herein, we aimed to investigate the capacity of zymosan to strengthen the vaccine response induced by an intranasal EV‐A71 vaccine. First, we confirmed its remarkable capacity to ignite innate signaling by upregulating cytokine production in primary DCs in vitro. Second, we verified its capacity to promote the vaccine immunogenicity in vivo after triple vaccination with EV‐A71, especially with the notable induction of virus‐specific IgA at multiple mucosae and the IL‐17‐producing splenic population after antigen reencounter. Lastly, we validated its capacity to improve vaccine efficacy in vivo after dual vaccination by furnishing neonatal protection against lethal infection. Our findings show that zymosan, at a preferable dosage, could augment the benefits of the intranasal vaccination to tackle EV‐A71 infection. This research provides a feasible strategy for preventing EV‐A71 infection with severe complications and contributes to the development of nasal spray vaccination.