Journal Article

Spontaneous C-cleavage of a truncated intein as fusion tag to produce tag-free VP1 inclusion body nanoparticle vaccine against CVB3-induced viral myocarditis by the oral route

Lu, Qian, Hu, JingPing, Xiong, Sidong, Qi, Xingmei

2019

Overview

Background Oral vaccine is highly desired for infectious disease which is caused by pathogens infection through the mucosal surface. The design of suitable vaccine delivery system is ongoing for the antigen protection from the harsh gastric environment and target to the Peyer’s patches to induce sufficient mucosal immune responses. Among various potential delivery systems, bacterial inclusion bodies have been widely used as delivery systems in the field of nanobiomedicine. However, a large number of heterologous complex proteins could be difficult to propagate in E. coli and fusion partners are often used to enhance target protein expression. As a safety concern the fusion protein need to be removed from the target protein to get tag-free protein, especially for the production of protein antigen in vaccinology. Until now, there is no report on how to remove fusion tag from inclusion body particles in vitro and in vivo. Coxsackievirus B3 (CVB3) is a leading causative agent of viral myocarditis and orally protein vaccine is high desired for CVB3-induced myocarditis. In this context, we explored a tag-free VP1 inclusion body nanoparticles production protocol though a truncated Ssp DnaX mini-intein spontaneous C-cleavage in vivo and also exploited the VP1 inclusion bodies as an oral protein nanoparticle vaccine to protect mice against CVB3-induced myocarditis. Results We successfully produced the tag-free VP1 inclusion body nanoparticle antigen of CVB3 and orally administrated to mice. The results showed that the tag-free VP1 inclusion body nanoparticles as an effective antigen delivery system targeting to the Peyer’s patches had the capacity to induce mucosal immunity as well as to efficiently protect mice from CVB3 induce myocarditis without any adjuvant. Then, we proposed the use of VP1 inclusion body nanoparticles as good candidate for oral vaccine to against CVB3-induced myocarditis. Conclusions Our tag-free inclusion body nanoparticles production procedure is easy and low cost and may have universal applicability to produce a variety of tag-free inclusion body nanoparticles for oral vaccine.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Administration, Oral / Animals / Antibodies, Viral - immunology / Antigens / Applied Microbiology / Biomedical materials / Biotechnology / Capsid Proteins - administration & dosage / Capsid Proteins - chemistry / Capsid Proteins - genetics / Capsid Proteins - immunology / Chemistry / Chemistry and Materials Science / Cleavage / Communicable diseases / Complications and side effects / Coxsackievirus infections / CVB3-induced viral myocarditis / Drug delivery systems / E coli / Enterovirus B, Human - chemistry / Enterovirus B, Human - genetics / Enterovirus B, Human - immunology / Enzymology / Escherichia coli / Fusion protein / Genetic Engineering / Health aspects / Heart diseases / Humans / Immune response / Immunity / Immunity, Mucosal / Inclusion bodies / Infection / Infectious diseases / Intein cleavage / Inteins / Male / Methods / Mice / Mice, Inbred BALB C / Microbial Genetics and Genomics / Microbiological research / Microbiology / Mucosal immunity / Myocarditis / Myocarditis - immunology / Myocarditis - prevention & control / Myocarditis - virology / Nanoparticles / Nanoparticles - chemistry / Oral protein vaccine / Pathogenic microorganisms / Prevention / Protein engineering / Protein expression / Proteins / Risk factors / Tag-free inclusion body particles / Transdermal drug delivery systems / Vaccines / Viral proteins / Viral vaccines / Viral Vaccines - administration & dosage / Viral Vaccines - chemistry / Viral Vaccines - genetics / Viral Vaccines - immunology / VP1 protein