title: Rational design of thermostable vaccines by engineered peptide-induced virus self-biomineralization under physiological conditions.
abstract: The development of vaccines against infectious diseases represents one of the most important contributions to medical science. However, vaccine-preventable diseases still cause millions of deaths each year due to the thermal instability and poor efficacy of vaccines. Using the human enterovirus type 71 vaccine strain as a model, we suggest a combined, rational design approach to improve the thermostability and immunogenicity of live vaccines by self-biomineralization. The biomimetic nucleating peptides are rationally integrated onto the capsid of enterovirus type 71 by reverse genetics so that calcium phosphate mineralization can be biologically induced onto vaccine surfaces under physiological conditions, generating a mineral exterior. This engineered self-biomineralized virus was characterized in detail for its unique structural, virological, and chemical properties. Analogous to many exteriors, the mineral coating confers some new properties on enclosed vaccines. The self-biomineralized vaccine can be stored at 26 °C for more than 9 d and at 37 °C for approximately 1 wk. Both in vitro and in vivo experiments demonstrate that this engineered vaccine can be used efficiently after heat treatment or ambient temperature storage, which reduces the dependence on a cold chain. Such a combination of genetic technology and biomineralization provides an economic solution for current vaccination programs, especially in developing countries that lack expensive refrigeration infrastructures.
authors.affiliation: Center for Biomaterials and Biopathways, Zhejiang University, Hangzhou 310027, China.
authors.forename: Guangchuan
authors.initials: G
authors.lastname: Wang
authors.forename: Rui-Yuan
authors.initials: RY
authors.lastname: Cao
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.forename: Lijuan
authors.initials: L
authors.lastname: Mo
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Han
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.forename: Xurong
authors.initials: X
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Deng
authors.forename: Ke
authors.initials: K
authors.lastname: Lyu
authors.forename: Shun-Ya
authors.initials: SY
authors.lastname: Zhu
authors.forename: E-De
authors.initials: ED
authors.lastname: Qin
authors.forename: Ruikang
authors.initials: R
authors.lastname: Tang
authors.forename: Cheng-Feng
authors.initials: CF
authors.lastname: Qin
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D029821:Enterovirus A, Human / Q000235:genetics* / Q000276:immunology; D005818:Genetic Engineering / Q000379:methods*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000737:chemistry*; D015202:Protein Engineering / Q000379:methods*; D013696:Temperature; D014709:Vero Cells; D014765:Viral Vaccines / Q000737:chemistry* / Q000276:immunology
chemical_list: D010455:Peptides; D014765:Viral Vaccines
keywords: genetic engineering; shell; vaccine design