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

Abstract

BackgroundClassical 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.ResultsOur 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.ConclusionsOur 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.

Plant‐made E2 glycoprotein single‐dose vaccine protects pigs against classical swine fever

“…In this work, we demonstrated that a N. benthamiana ‐derived CSFV E2 vaccine protected pigs from a lethal CSFV challenge, even after a single‐dose vaccination as recently demonstrated in pigs vaccinated with insect‐derived E2 formulated with KNB adjuvant (Madera et al ., , ) Robust anti‐E2 IgG and CSFV‐neutralizing antibody responses were generated in vaccinated pigs. Pig groups receiving two doses of E2 vaccine showed no clinical signs, low or no viremia in serum and nasal swabs and continuous weight gain post challenge.…”

“…We formulated pE2 with one of two adjuvants: (i) TS6 and (ii) KNB (Kansas State University, Manhattan, KS). In addition, efficacy was determined with these pE2 adjuvant formulations and an insect cell-derived E2 (iE2) KNB-adjuvanted vaccine, KNB-E2 (Madera et al, 2016). The six treatment groups are summarized in Table 1.…”

“…Towards development of an improved CSFV subunit vaccine, Madera et al . recently demonstrated protection against CSFV infection in pigs receiving a single dose of a baculoviral/insect cell‐based E2 histidine‐tagged subunit vaccine when formulated in the new KNB adjuvant (Galliher‐Beckley et al ., ; Madera et al ., ). Unfortunately, antigen production using the baculovirus/insect cell expression system remains expensive at manufacturing scale and thus limits wide‐spread deployment of this particular subunit vaccine.…”

“…However, several product profile limitations have been recognized for the baculovirus-derived CSFV vaccine including: (i) a slow protective response, (ii) limited protection against vertical transmission and (iii) viral shedding from vaccinates Zaabel et al, 2012). Towards development of an improved CSFV subunit vaccine, Madera et al recently demonstrated protection against CSFV infection in pigs receiving a single dose of a baculoviral/insect cell-based E2 histidine-tagged subunit vaccine when formulated in the new KNB adjuvant (Galliher-Beckley et al, 2015;Madera et al, 2016). Unfortunately, antigen production using the baculovirus/insect cell expression system remains expensive at manufacturing scale and thus limits widespread deployment of this particular subunit vaccine.…”

Virus-Like Particles as an Instrument of Vaccine Production

“…Another example is classical swine fever virus (CSFV). It has been demonstrated that the E2 viral protein produced in the baculovirus expression system induces the synthesis of CSFV-neutralizing antibodies in pigs [23].…”