Sanipa Suradhat1, Piya Wongyanin2, Sawang Kesdangsakonwut3, Komkrich Teankum3, Mongkol Lumyai4, Sittikorn Triyarach4, Roongroje Thanawongnuwech5. 1. Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Pathumwan, Bangkok 10330, Thailand. Electronic address: Sanipa.S@chula.ac.th. 2. Inter-department of Medical Microbiology, Graduate School, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand. 3. Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand. 4. Thai-Denmark Swine Breeder Public Company Limited, Bang-na, Bangkok 10260, Thailand. 5. Faculty of Veterinary Science, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand; Center of Excellence in Emerging Infectious Diseases in Animals, Chulalongkorn University (CU-EIDAs), Pathumwan, Bangkok 10330, Thailand.
Abstract
BACKGROUND: Viral-induced interleukin (IL)-10 and regulatory T lymphocytes (Tregs) are believed to play a major role in shaping the immunological and clinical outcomes following Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection. Recently, it has been shown that PRRSV nucleocapsid (N) protein can induce IL-10 production which is essential for induction of PRRSV-specific Tregs. We hypothesized that immunity to N protein should reduce PRRSV-induced negative immunomodulatory effects which will be essential for establishing proper anti-PRRSV immunity in infected pigs. OBJECTIVES: To investigate the immunomodulatory effects of DNA vaccine encoding a linearized, truncated form of PRRSV-N protein (pORF7t) which was designed to preferentially induce cell-mediated immunity against PRRSV N protein. METHOD: Immunomodulatory effects of the novel DNA vaccine were investigated in an experimental vaccinated-challenged model. In addition, long-term immunomodulatory effects of the DNA vaccine were investigated in vaccinated pigs kept at the PRRSV-positive environment until the end of the fattening period. Pigs were vaccinated either prior to or following natural PRRSV infection. RESULT: The results indicated that pORF7t could modulate the anti-PRRSV immune responses and promote the control of viral replication in the vaccinated-challenged pigs. Immunized pigs exhibited increased numbers of PRRSV-specific activated CD4(+)CD25(+) lymphocytes, reduced numbers of PRRSV-specific Tregs, and rapid viral clearance following infection. In a long-term study, regardless of the time of vaccination, DNA vaccine could modulate the host immune responses, resulted in enhanced PRRSV-specific IFN-γ producing cells, and reduced numbers of PRRSV-specific Tregs, without evidence of enhanced antibody responses. No vaccine adverse reaction was observed throughout the study. CONCLUSION: This study revealed the novel concept that PRRSV-specific immunity can be modulated by induction of cell-mediated immunity against the nucleocapsid protein. This concept could potentially benefit the development of PRRSV management and control strategies.
BACKGROUND: Viral-induced interleukin (IL)-10 and regulatory T lymphocytes (Tregs) are believed to play a major role in shaping the immunological and clinical outcomes following Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection. Recently, it has been shown that PRRSV nucleocapsid (N) protein can induce IL-10 production which is essential for induction of PRRSV-specific Tregs. We hypothesized that immunity to N protein should reduce PRRSV-induced negative immunomodulatory effects which will be essential for establishing proper anti-PRRSV immunity in infected pigs. OBJECTIVES: To investigate the immunomodulatory effects of DNA vaccine encoding a linearized, truncated form of PRRSV-N protein (pORF7t) which was designed to preferentially induce cell-mediated immunity against PRRSV N protein. METHOD: Immunomodulatory effects of the novel DNA vaccine were investigated in an experimental vaccinated-challenged model. In addition, long-term immunomodulatory effects of the DNA vaccine were investigated in vaccinated pigs kept at the PRRSV-positive environment until the end of the fattening period. Pigs were vaccinated either prior to or following natural PRRSVinfection. RESULT: The results indicated that pORF7t could modulate the anti-PRRSV immune responses and promote the control of viral replication in the vaccinated-challenged pigs. Immunized pigs exhibited increased numbers of PRRSV-specific activated CD4(+)CD25(+) lymphocytes, reduced numbers of PRRSV-specific Tregs, and rapid viral clearance following infection. In a long-term study, regardless of the time of vaccination, DNA vaccine could modulate the host immune responses, resulted in enhanced PRRSV-specific IFN-γ producing cells, and reduced numbers of PRRSV-specific Tregs, without evidence of enhanced antibody responses. No vaccine adverse reaction was observed throughout the study. CONCLUSION: This study revealed the novel concept that PRRSV-specific immunity can be modulated by induction of cell-mediated immunity against the nucleocapsid protein. This concept could potentially benefit the development of PRRSV management and control strategies.
Authors: Tatjana Sattler; Jutta Pikalo; Eveline Wodak; Sandra Revilla-Fernández; Adi Steinrigl; Zoltán Bagó; Ferdinand Entenfellner; Jean-Baptiste Claude; Floriane Pez; Maela Francillette; Friedrich Schmoll Journal: BMC Vet Res Date: 2018-04-19 Impact factor: 2.741