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

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 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.


Related in: MedlinePlus

Pigs vaccinated with KNB-E2 were protected from CSFV-induced leukopenia. Blood cell counts including WBC (a), lymphocytes (b), neutrophils (c), and monocytes (d) were monitored on 0, 3, 6, 9, 12, and 15 DPC. A slight decrease but not statistically different in the numbers of WBC, lymphocytes, and neutrophils of all vaccinated pigs were observed at 3 DPC and 6 DPC, these numbers were recovered by 9 DPC. Data are mean ± SEM for five pigs per group. *p < 0.05
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Fig3: Pigs vaccinated with KNB-E2 were protected from CSFV-induced leukopenia. Blood cell counts including WBC (a), lymphocytes (b), neutrophils (c), and monocytes (d) were monitored on 0, 3, 6, 9, 12, and 15 DPC. A slight decrease but not statistically different in the numbers of WBC, lymphocytes, and neutrophils of all vaccinated pigs were observed at 3 DPC and 6 DPC, these numbers were recovered by 9 DPC. Data are mean ± SEM for five pigs per group. *p < 0.05

Mentions: To test the efficacy of CSFV E2 subunit vaccine, pigs in both vaccinated groups and the (−/+) group were challenged with CSFV isolate Honduras/1997. After CSFV inoculation, pigs in the (−/+) group displayed clinical signs of CSF, including high fever (Fig. 2a), loss of body weight (Fig. 2b), severe leukopenia (Fig. 3), convulsion, diarrhea, and one of the five pigs, #59, had to be euthanized due to severe clinical symptoms at 9 DPC. In contrast, pigs vaccinated with KNB-E2 - the E2 subunit vaccine (One-dose and Two-dose groups) did not show elevated body temperature after CSFV challenge (Fig. 2a). More importantly, body weight gains in the two vaccinated groups were almost identical to that in healthy control pigs (−/−) before and after CSFV challenge (Fig. 2b).Fig. 2


Pigs immunized with a novel E2 subunit vaccine are protected from subgenotype heterologous classical swine fever virus challenge
Pigs vaccinated with KNB-E2 were protected from CSFV-induced leukopenia. Blood cell counts including WBC (a), lymphocytes (b), neutrophils (c), and monocytes (d) were monitored on 0, 3, 6, 9, 12, and 15 DPC. A slight decrease but not statistically different in the numbers of WBC, lymphocytes, and neutrophils of all vaccinated pigs were observed at 3 DPC and 6 DPC, these numbers were recovered by 9 DPC. Data are mean ± SEM for five pigs per group. *p < 0.05
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getmorefigures.php?uid=PMC5016919&req=5

Fig3: Pigs vaccinated with KNB-E2 were protected from CSFV-induced leukopenia. Blood cell counts including WBC (a), lymphocytes (b), neutrophils (c), and monocytes (d) were monitored on 0, 3, 6, 9, 12, and 15 DPC. A slight decrease but not statistically different in the numbers of WBC, lymphocytes, and neutrophils of all vaccinated pigs were observed at 3 DPC and 6 DPC, these numbers were recovered by 9 DPC. Data are mean ± SEM for five pigs per group. *p < 0.05
Mentions: To test the efficacy of CSFV E2 subunit vaccine, pigs in both vaccinated groups and the (−/+) group were challenged with CSFV isolate Honduras/1997. After CSFV inoculation, pigs in the (−/+) group displayed clinical signs of CSF, including high fever (Fig. 2a), loss of body weight (Fig. 2b), severe leukopenia (Fig. 3), convulsion, diarrhea, and one of the five pigs, #59, had to be euthanized due to severe clinical symptoms at 9 DPC. In contrast, pigs vaccinated with KNB-E2 - the E2 subunit vaccine (One-dose and Two-dose groups) did not show elevated body temperature after CSFV challenge (Fig. 2a). More importantly, body weight gains in the two vaccinated groups were almost identical to that in healthy control pigs (−/−) before and after CSFV challenge (Fig. 2b).Fig. 2

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.


Related in: MedlinePlus