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

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ABSTRACT

Background: Classical swine fever (CSF) or hog cholera is a highly contagious swine viral disease. 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. We hypothesize that a vaccine consisting of a suitable adjuvant and recombinant E2 with natural conformation may induce a similar level of protection as the MLV vaccine.

Results: Our 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. 10 pigs (3 weeks old, 5 pigs/group) were immunized intramuscularly with one dose or two doses (3 weeks apart) KNB-E2, and 10 more control pigs were administered normal saline solution only. Two weeks after the second vaccination, all KNB-E2 vaccinated pigs and 5 control pigs were challenged with 5 × 105 TCID50 CSFV Honduras/1997 (Genotype 1.3, 1 ml intramuscular, 1 ml intranasal). It was found that while control pigs infected with CSFV stopped growing and developed high fever (>40 °C), high level CSFV load in blood and nasal fluid, and severe leukopenia 3–14 days post challenge, all KNB-E2 vaccinated pigs continued to grow as control pigs without CSFV exposure, did not show any fever, had low or undetectable 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 and anti-CSFV neutralizing antibodies.

Conclusions: Our studies provide direct evidence that pigs immunized with one dose KNB-E2 can be protected clinically from CSFV challenge. This protection is likely mediated by high levels of E2-specific and anti-CSFV neutralizing antibodies.

No MeSH data available.


E2-specific antibodies were detected by ELISA only in pigs vaccinated with KNB-E2 before and after challenge. E2- and Erns-specific antibodies were measured by ELISA as we described in Materials and Methods. a E2-specific antibody in serum samples collected after vaccination and challenge. b Erns-specific antibody in serum samples collected at 0 DPC and 15 DPC. Data are shown as mean ± SEM for five pigs per group. * p < 0.05
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Fig4: E2-specific antibodies were detected by ELISA only in pigs vaccinated with KNB-E2 before and after challenge. E2- and Erns-specific antibodies were measured by ELISA as we described in Materials and Methods. a E2-specific antibody in serum samples collected after vaccination and challenge. b Erns-specific antibody in serum samples collected at 0 DPC and 15 DPC. Data are shown as mean ± SEM for five pigs per group. * p < 0.05

Mentions: As shown in Fig. 4a, all vaccinated pigs developed E2-specific antibody after immunization. E2-specific antibody level in the One-dose group increased dramatically after challenge and was even higher than that in the Two-dose group at 9 DPC. The level of E2-specific antibody in the Two-dose group increased dramatically after the boost vaccination, but decreased significantly in the first 9 days post challenge. E2-specific antibody was not detected in control pigs before or after the challenge (Fig. 4a). In contrast to E2-spepcific antibody response, Erns-specific antibody was only detected in the (−/+) pigs at 15 DPC (Fig. 4b).Fig. 4


Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype heterologous classical swine fever virus challenge
E2-specific antibodies were detected by ELISA only in pigs vaccinated with KNB-E2 before and after challenge. E2- and Erns-specific antibodies were measured by ELISA as we described in Materials and Methods. a E2-specific antibody in serum samples collected after vaccination and challenge. b Erns-specific antibody in serum samples collected at 0 DPC and 15 DPC. Data are shown as mean ± SEM for five pigs per group. * p < 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5016919&req=5

Fig4: E2-specific antibodies were detected by ELISA only in pigs vaccinated with KNB-E2 before and after challenge. E2- and Erns-specific antibodies were measured by ELISA as we described in Materials and Methods. a E2-specific antibody in serum samples collected after vaccination and challenge. b Erns-specific antibody in serum samples collected at 0 DPC and 15 DPC. Data are shown as mean ± SEM for five pigs per group. * p < 0.05
Mentions: As shown in Fig. 4a, all vaccinated pigs developed E2-specific antibody after immunization. E2-specific antibody level in the One-dose group increased dramatically after challenge and was even higher than that in the Two-dose group at 9 DPC. The level of E2-specific antibody in the Two-dose group increased dramatically after the boost vaccination, but decreased significantly in the first 9 days post challenge. E2-specific antibody was not detected in control pigs before or after the challenge (Fig. 4a). In contrast to E2-spepcific antibody response, Erns-specific antibody was only detected in the (−/+) pigs at 15 DPC (Fig. 4b).Fig. 4

View Article: PubMed Central - PubMed

ABSTRACT

Background: Classical swine fever (CSF) or hog cholera is a highly contagious swine viral disease. 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. We hypothesize that a vaccine consisting of a suitable adjuvant and recombinant E2 with natural conformation may induce a similar level of protection as the MLV vaccine.

Results: Our 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. 10 pigs (3&nbsp;weeks old, 5 pigs/group) were immunized intramuscularly with one dose or two doses (3&nbsp;weeks apart) KNB-E2, and 10 more control pigs were administered normal saline solution only. Two weeks after the second vaccination, all KNB-E2 vaccinated pigs and 5 control pigs were challenged with 5&thinsp;&times;&thinsp;105 TCID50 CSFV Honduras/1997 (Genotype 1.3, 1&nbsp;ml intramuscular, 1&nbsp;ml intranasal). It was found that while control pigs infected with CSFV stopped growing and developed high fever (&gt;40&nbsp;&deg;C), high level CSFV load in blood and nasal fluid, and severe leukopenia 3&ndash;14&nbsp;days post challenge, all KNB-E2 vaccinated pigs continued to grow as control pigs without CSFV exposure, did not show any fever, had low or undetectable 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 and anti-CSFV neutralizing antibodies.

Conclusions: Our studies provide direct evidence that pigs immunized with one dose KNB-E2 can be protected clinically from CSFV challenge. This protection is likely mediated by high levels of E2-specific and anti-CSFV neutralizing antibodies.

No MeSH data available.