Effective improvements to the live-attenuated Newcastle disease virus vaccine by polyethylenimine-based biomimetic silicification

Jinjin Zhang; Yanhong Ji; Zhengxiang Wang; Yane Jia; Qiyun Zhu

doi:10.1016/j.vaccine.2021.12.054

Effective improvements to the live-attenuated Newcastle disease virus vaccine by polyethylenimine-based biomimetic silicification

Vaccine. 2022 Feb 7;40(6):886-896. doi: 10.1016/j.vaccine.2021.12.054. Epub 2022 Jan 3.

Authors

Jinjin Zhang¹, Yanhong Ji¹, Zhengxiang Wang¹, Yane Jia¹, Qiyun Zhu²

Affiliations

¹ State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, PR China.
² State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, PR China. Electronic address: zhuqiyun@caas.cn.

PMID: 34991927
DOI: 10.1016/j.vaccine.2021.12.054

Abstract

Live and killed vaccines impart a significant role in preventing of Newcastle disease (ND) in China. Vaccine efficacy could be ameliorated by improving vaccine-induced cellular immunity and antibody persistency. Previous studies substantiated the potency of silicon dioxide (SiO₂) in the control-release of drugs and as a vaccine adjuvant, and polyethylenimine (PEI) merits as a mucosal adjuvanticity with electro-positivity. The present study employed SiO₂ and PEI to prepare biomimetic silicon mineralized nanoparticle G7M@SiO₂-PEI and microparticle (SiO₂ + PEI)@G7M vaccines of G7M, a candidate for live attenuated vaccine of genotype VII Newcastle disease virus (NDV). The zeta potential experiment confirmed the significant increase in the average zeta potential of the nanoparticle G7M@SiO₂-PEI and microparticle (SiO₂ + PEI)@G7M relative to G7M before mineralization. The results of RT-qPCR revealed more than 99% mineralization efficiency of the G7M@SiO₂-PEI and (SiO₂ + PEI)@G7M. The morphology detected by transmission electron microscopy reported that the diameters of G7M@SiO₂-PEI were similar to those of G7M, while for (SiO₂ + PEI)@G7M, it was about five times larger than that of G7M. Silicon was detected on the surface of both mineralization particles, except for G7M, as observed from the elemental distribution detected by elemental mapping and energy dispersive X-ray spectrogram. Indirect immunofluorescence assays validated that mineralization virus have replicated ability in BHK-21F cells. In vivo experiments revealed higher than 5.50 log₂ of antibody in nanoparticles G7M@SiO₂-PEI group until 10-week post-vaccination, and significant proliferation of antigen-specific CD3⁺CD4⁺ in nanoparticles G7M@SiO₂-PEI immunized group corroborated improved cellular immune responses. Vaccines provided full protection to the immunized chickens, whereas all the chickens receiving mock immunizations succumbed to the disease. Overall, our study concluded the efficacy of biomimetic mineralization of live attenuated vaccine in nanoparticles to improve humoral and cellular immune responses.

Keywords: Biomimetic mineralization; Newcastle disease virus; Polyethylenimine; Silicon dioxide; Vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Viral
Biomimetics
Chickens
Newcastle Disease*
Newcastle disease virus
Polyethyleneimine
Poultry Diseases* / prevention & control
Silicon Dioxide
Vaccines, Attenuated
Viral Vaccines*

Substances

Antibodies, Viral
Vaccines, Attenuated
Viral Vaccines
Silicon Dioxide
Polyethyleneimine