Use of praziquantel as an adjuvant enhances protection and Tc-17 responses to killed H5N1 virus vaccine in mice.

Abstract

BACKGROUND:

H5N1 is a highly pathogenic influenza A virus, which can cause severe illness or even death in humans. Although the widely used killed vaccines are able to provide some protection against infection via neutralizing antibodies, cytotoxic T-lymphocyte responses that are thought to eradicate viral infections are lacking.

METHODOLOGY/PRINCIPAL FINDINGS:

Aiming to promote cytotoxic responses against H5N1 infection, we extended our previous finding that praziquantel (PZQ) can act as an adjuvant to induce IL-17-producing CD8(+) T cells (Tc17). We found that a single immunization of 57BL/6 mice with killed viral vaccine plus PZQ induced antigen-specific Tc17 cells, some of which also secreted IFN-γ. The induced Tc17 had cytolytic activities. Induction of these cells was impaired in CD8 knockout (KO) or IFN-γ KO mice, and was even lower in IL-17 KO mice. Importantly, the inoculation of killed vaccine with PZQ significantly reduced virus loads in the lung tissues and prolonged survival. Protection against H5N1 virus infection was obtained by adoptively transferring PZQ-primed wild type CD8(+) T cells and this was more effective than transfer of activated IFN-γ KO or IL-17 KO CD8(+) T cells.

CONCLUSIONS/SIGNIFICANCE:

Our results demonstrated that adding PZQ to killed H5N1 vaccine could promote broad Tc17-mediated cytotoxic T lymphocyte activity, resulting in improved control of highly pathogenic avian influenza virus infection.

• Authors: Qiang Zou, Yanxin Hu, Jia Xue, Xiaoxu Fan, Yi Jin, Xianghua Shi, Di Meng, Xianzheng Wang, Congcong Feng, Xiaoping Xie, Yizhi Zhang, Youmin Kang, Xiaoxuan Liang, Bing Wu, Ming Wang, Bin Wang
• Journal: PloS one (PLoS One) Vol. 7 Issue 4 Pg. e34865 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22529945 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Cytokines
• Influenza Vaccines
• Vaccines, Inactivated
• Praziquantel

Topics

• Adjuvants, Immunologic (therapeutic use)
• Animals
• Cytokines (biosynthesis)
• Cytotoxicity, Immunologic
• Female
• Humans
• Influenza A Virus, H5N1 Subtype (immunology)
• Influenza Vaccines (administration & dosage, immunology)
• Lymphocyte Activation
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Orthomyxoviridae Infections (immunology, mortality, prevention & control)
• Praziquantel (therapeutic use)
• T-Lymphocytes, Cytotoxic (immunology)
• Vaccines, Inactivated (administration & dosage, immunology)