Short-Fragment DNA Residue from Vaccine Purification Processes Promotes Immune Response to the New Inactivated EV71 Vaccine by Upregulating TLR9 mRNA

Jie Shao; Fan Gao; Hui-Juan Lin; Qun-Ying Mao; Pan Chen; Xing Wu; Xin Yao; Wei Kong; Zheng-Lun Liang

doi:10.1371/journal.pone.0153867

Short-Fragment DNA Residue from Vaccine Purification Processes Promotes Immune Response to the New Inactivated EV71 Vaccine by Upregulating TLR9 mRNA

PLoS One. 2016 Apr 15;11(4):e0153867. doi: 10.1371/journal.pone.0153867. eCollection 2016.

Authors

Jie Shao^{1

2}, Fan Gao², Hui-Juan Lin², Qun-Ying Mao², Pan Chen², Xing Wu², Xin Yao², Wei Kong¹, Zheng-Lun Liang²

Affiliations

¹ School of Life Sciences, Jilin University, Changchun, P.R. China.
² National Institutes for Food and Drug Control, Beijing, P.R. China.

Abstract

To reduce potential oncogenic long genomic DNA in vaccines, nuclease treatment has been applied in the purification processes. However, this action increased the residue of short-fragment DNA and its effect on vaccine potency was still elusive. In this study, we found residual sf-DNA in an inactivated EV71 vaccine could enhance humoral immune response in mice. Ag stimulation in vitro and vaccine injection in vivo revealed that TLR9 transcription level was elevated, indicating that sf-DNA could activate TLR9. These new findings will help us to understand the molecular mechanism induced by vero-cell culture-derived vaccines.

Publication types

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

MeSH terms

Animals
Antibodies, Neutralizing / immunology
Chlorocebus aethiops
CpG Islands
DNA / chemistry*
Enterovirus A, Human
Enterovirus Infections / immunology*
Female
Immunity, Humoral*
Injections, Intraperitoneal
Lymphocytes / cytology
Mice
Mice, Inbred C57BL
Mice, Knockout
RNA, Messenger / metabolism
Real-Time Polymerase Chain Reaction
Spleen / metabolism
Toll-Like Receptor 9 / metabolism*
Up-Regulation*
Vaccines, Inactivated / immunology
Vero Cells
Viral Vaccines / immunology*

Substances

Antibodies, Neutralizing
RNA, Messenger
Toll-Like Receptor 9
Vaccines, Inactivated
Viral Vaccines
DNA

Grants and funding

This work was supported by the National 12th Five Major Special Projects Funding Program (No. 2012ZX10004701) from the Ministry of Science and Technology of the People’s Republic of China, URL: http://www.nmp.gov.cn/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.