Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
Vaccine. 2012 Oct 19;30(47):6642-8. doi: 10.1016/j.vaccine.2012.08.071. Epub 2012 Sep 7.
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.
柯萨奇病毒 A16（CVA16）是手足口病（HFMD）的主要病原体之一，近年来在亚太地区流行。然而，目前尚无预防 HFMD 的疫苗。在这里，我们报告了一种基于病毒样颗粒（VLP）的实验性 CVA16 疫苗的开发。使用重组杆状病毒，通过共表达 CVA16 的 P1 和 3CD 蛋白，在昆虫细胞中产生 CVA16 VLP。生化和生物物理分析表明，CVA16 VLP 由加工的 VP0、VP1 和 VP3 组成，呈约 30nm 球形颗粒。VLPs 免疫可在小鼠中引发强烈的 CVA16 特异性血清抗体反应。抗-VLP 血清在体外强烈中和同源和异源 CVA16 株。更重要的是，用抗-VLP 血清进行被动免疫可赋予新生小鼠免受致死性 CVA16 攻击的保护，表明存在体液保护机制。总之，我们的研究结果代表了开发针对 CVA16 感染的安全有效的疫苗的成功的第一步。
