Highly efficient expression of interleukin-2 under the control of rabbit β-globin intron II gene enhances protective immune responses of porcine reproductive and respiratory syndrome (PRRS) DNA vaccine in pigs

Yijun Du; Yu Lu; Xinglong Wang; Jing Qi; Jiyu Liu; Yue Hu; Feng Li; Jiaqiang Wu; Lihui Guo; Junzhen Liu; Haiying Tao; Wenbo Sun; Lei Chen; Xiaoyan Cong; Sufang Ren; Jianli Shi; Jun Li; Jinbao Wang; Baohua Huang; Renzhong Wan

doi:10.1371/journal.pone.0090326

Highly efficient expression of interleukin-2 under the control of rabbit β-globin intron II gene enhances protective immune responses of porcine reproductive and respiratory syndrome (PRRS) DNA vaccine in pigs

PLoS One. 2014 Mar 6;9(3):e90326. doi: 10.1371/journal.pone.0090326. eCollection 2014.

Authors

Yijun Du¹, Yu Lu², Xinglong Wang³, Jing Qi¹, Jiyu Liu⁴, Yue Hu⁵, Feng Li⁶, Jiaqiang Wu⁴, Lihui Guo⁴, Junzhen Liu⁴, Haiying Tao⁴, Wenbo Sun⁴, Lei Chen¹, Xiaoyan Cong¹, Sufang Ren⁴, Jianli Shi⁴, Jun Li⁴, Jinbao Wang⁷, Baohua Huang⁴, Renzhong Wan⁵

Affiliations

¹ School of Life Sciences, Shandong University, Jinan, China; Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China.
² National Research Center of Veterinary Biologicals Engineering and Technology, Jiangsu Academy of Agricultural Sciences, Nanjing, China.
³ College of Veterinary Medicine, Northwest A&F University, Yangling, China.
⁴ Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China.
⁵ College of Animal Science & Veterinary Medicine, Shandong Agricultural University, Tai'an, China.
⁶ Department of Biology and Microbiology, Department of Veterinary and Biomedical Sciences, South Dakota State University, Brookings, South Dakota, United States of America.
⁷ School of Life Sciences, Shandong University, Jinan, China; Shandong Key Laboratory of Animal Disease Control and Breeding, Institute of Animal Science and Veterinary Medicine, Shandong Academy of Agricultural Sciences, Jinan, China; College of Animal Science & Veterinary Medicine, Shandong Agricultural University, Tai'an, China.

Abstract

Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) had caused catastrophic losses in swine industry in China. The current inactivated vaccine provided only limited protection, and the attenuated live vaccine could protect piglets against the HP-PRRSV but there was a possibility that the attenuated virus returned to high virulence. In this study, the eukaryotic expression vector pVAX1© was modified under the control of rabbit β-globin intron II gene and the modified vector pMVAX1© was constructed. Porcine interleukin-2 (IL-2) and GP3-GP5 fusion protein of HP-PRRSV strain SD-JN were highly expressed by pMVAX1©. Mice inoculated with pMVAX1©-GP35 developed significantly higher PRRSV-specific antibody responses and T cell proliferation than those vaccinated with pVAX1©-GP35. pMVAX1©-GP35 was selected as PRRS DNA vaccine candidate and co-administrated with pVAX1©-IL-2 or pMVAX1©-IL-2 in pigs. pMVAX1©-IL-2+pMVAX1©-GP35 could provide enhanced PRRSV-specific antibody responses, T cell proliferation, Th1-type and Th2-type cytokine responses and CTL responses than pMVAX1©-GP35 and pVAX1©-IL-2+pMVAX1©-GP35. Following homologous challenge with HP-PRRSV strain SD-JN, similar with attenuated PRRS vaccine group, pigs inoculated with pMVAX1©-IL-2+pMVAX1©-GP35 showed no clinical signs, almost no lung lesions and no viremia, as compared to those in pMVAX1©-GP35 and pVAX1©-IL-2+pMVAX1©-GP35 groups. It indicated that pMVAX1©-IL-2 effectively increases humoral and cell mediated immune responses of pMVAX1©-GP35. Co-administration of pMVAX1©-IL-2 and pMVAX1©-GP35 might be attractive candidate vaccines for preventing HP-PRRSV infections.

Publication types

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

MeSH terms

Animals
Antibodies, Viral / blood
Antibodies, Viral / immunology
Blotting, Western
Cell Proliferation
Cytokines / immunology
Cytokines / metabolism
Female
Gene Expression / immunology
Genetic Vectors / genetics
Glycoproteins / genetics
Glycoproteins / immunology
Glycoproteins / metabolism
HEK293 Cells
Humans
Immunity, Cellular / immunology
Immunity, Humoral / immunology
Interleukin-2 / genetics
Interleukin-2 / immunology*
Interleukin-2 / metabolism
Introns / genetics
Lymphocytes / immunology
Lymphocytes / metabolism
Mice, Inbred BALB C
Porcine Reproductive and Respiratory Syndrome / immunology*
Porcine Reproductive and Respiratory Syndrome / prevention & control
Porcine Reproductive and Respiratory Syndrome / virology
Porcine respiratory and reproductive syndrome virus / genetics
Porcine respiratory and reproductive syndrome virus / immunology*
Porcine respiratory and reproductive syndrome virus / metabolism
Rabbits
Reverse Transcriptase Polymerase Chain Reaction
Swine
Vaccines, DNA / administration & dosage
Vaccines, DNA / genetics
Vaccines, DNA / immunology*
Viral Proteins / genetics
Viral Proteins / immunology
Viral Proteins / metabolism
beta-Globins / genetics

Substances

Antibodies, Viral
Cytokines
Glycoproteins
Interleukin-2
Vaccines, DNA
Viral Proteins
beta-Globins

Grants and funding

This work was supported by the National Natural Science Foundation (31170146, 31100119 and 31370189), Special Fund for Agro-scientific Research in the Public Interest (201303046), Research Award Fund for Outstanding Young Scientist of Shandong Province (BS2012NY012), a grant from the China Postdoctoral Science Foundation (2012M521341), and Shandong Province Postdoctoral Special Fund for Innovative Projects (201203036). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.