Pigs immunized with a novel E2 subunit vaccine are protected from heterologous classical swine fever virus challenge

Authors: MADERA, RACHEL - Kansas State University; GONG, WENJIE - Kansas State University; WANG, LIHUA - Kansas State University; BURAKOVA, YULIA - Kansas State University; LLEELLISH, KAREN - Kansas State University; GALLIHER-BECKLEY, AMY - Kansas State University; NIETFELD, JEROME - Kansas State University; HENNINGSON, JAIME - Kansas State University; JIA, KAIMIN - Kansas State University; LI, PING - Kansas State University; BAI, JIANFA - Kansas State University; SCHLUP, JOHN - Kansas State University; McVey, David; TU, CHANGCHUN - Kansas State University; SHI, JISHU - Kansas State University

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/9/2016
Publication Date: 9/9/2016
Citation: Madera, R., Gong, W., Wang, L., Burakova, Y., Lleellish, K., Galliher-Beckley, A., Nietfeld, J., Henningson, J., Jia, K., Li, P., Bai, J., Schlup, J., Mcvey, D.S., Tu, C., Shi, J. 2016. Pigs immunized with a novel E2 subunit vaccine are protected from heterologous classical swine fever virus challenge. Virology. 10/1186.

Interpretive Summary: Classical swine fever (CSF) or hog cholera is a highly contagious swine viral disease that has been eradicated from the United States. But many CSF endemic countries have to use routine vaccination with modified live virus (MLV) vaccines to prevent and control CSF. However, it is impossible to serologically differentiate MLV vaccinated pigs from those infected with CSF virus (CSFV). The aim of this study is to develop a one-dose E2-subunit vaccine that can provide protection against CSFV challenge. The experimental vaccine KNB-E2 was formulated with the recombinant E2 protein (Genotype 1.1) expressed by insect cells and an oil-in-water emulsion based adjuvant. All KNB-E2 vaccinated pigs continued to gain weight, did not have clinical signs or fever typical of CSF and did not have evidence of viral infection with CSFV. The vaccinated pigs developed a strong antibody responses to the CSFV. These studies provide the first evidence that pigs immunized with one dose KNB-E2 vaccine can be protected clinically from CSFV challenge infection. This protection is likely mediated by a strong, virus-neutralizing antibody response in the vaccinated pigs.

Technical Abstract: Background: Classical swine fever (CSF) or hog cholera is a highly contagious swineviral disease. CSF endemic countries have to use routine vaccination with modifiedlive virus (MLV) vaccines to prevent and control CSF. However, it is impossible toserologically differentiate MLV vaccinated pigs from those infected with CSF virus(CSFV). The aim of this study is to develop a one-dose E2-subunit vaccine that canprovide protection against CSFV challenge. We hypothesize that a vaccine consistingof a suitable adjuvant and recombinant E2 with natural conformation may induce asimilar level of protection as the MLV vaccine. Methods: Our experimental vaccine KNB-E2 was formulated with the recombinant E2protein (Genotype 1.1) expressed by insect cells and an oil-in-water emulsion basedadjuvant. 10 pigs (3 weeks old, 5 pigs/group) were immunized intramuscularly with onedose or two doses (3 weeks apart) KNB-E2, and 10 more control pigs wereadministered normal saline solution only. Two weeks after the second vaccination, allKNB-E2 vaccinated pigs and 5 control pigs were challenged with 5x105 TCID50 CSFVHonduras/1997 (Genotype 1.3, 1 ml intramuscular, 1 ml intranasal). Results: It was found that while control pigs infected with CSFV stopped growing anddeveloped high fever (>40oC), high level CSFV load in blood and nasal fluid, andsevere leukopenia 3 - 14 days post challenge, all KNB-E2 vaccinated pigs continued togrow as control pigs without CSFV exposure, did not show any fever, had low orundetectable level of CSFV in blood and nasal fluid. At the time of CSFV challenge,only pigs immunized with KNB-E2 developed high levels of E2-specific antibodies andanti-CSFV neutralizing antibodies. Conclusions: Our studies provide the first evidence that pigs immunized with one doseKNB-E2 can be protected clinically from CSFV challenge. This protection is likelymediated by high levels of E2-specific and anti-CSFV neutralizing antibodies.