A virus-like particle vaccine for coxsackievirus A16 potently elicits neutralizing antibodies that protect mice against lethal challenge

Coxsackievirus A16 (CVA16) is one of the main causative agents of hand, foot and mouth disease (HFMD), which has been prevalent in the Asia-Pacific region over the last several years. However, no vaccine is yet available to prevent HFMD. Here we report the development of a virus-like particle (VLP) based experimental CVA16 vaccine. CVA16 VLPs were produced in insect cells by co-expression of the P1 and 3CD proteins of CVA16 using recombinant baculoviruses. Biochemical and biophysical analyses showed that CVA16 VLPs consisted of processed VP0, VP1 and VP3, and were present as ≈ 30 nm spherical particles. Immunization with VLPs potently elicited CVA16-specific serum antibody responses in mice. Anti-VLP sera strongly neutralized in vitro both the homologous and heterologous strains of CVA16. More importantly, passive immunization with anti-VLP sera conferred protection against lethal CVA16 challenge in neonate mice, indicating a humoral mechanism of protection. Collectively, our results represent a successful first step toward the development of a safe and effective vaccine against CVA16 infection.