For vaccination against classical swine fever virus (CSFV), it is strongly desirable to induce a rapid and long lasting protection. At present, only live attenuated CSFV vaccines have shown early onset of protection, differing with the recombinant subunit-based vaccines reported so far. Recently, a new vaccine formulation based on E2 envelope viral glycoprotein produced in the milk of goats (E2his) has been shown to induce a highly protective response in pigs against CSFV infection. Pigs immunized with a single dose of this vaccine candidate, formulated as a water-in oil emulsion, elicited an effective response against CSF as early as 7 days post-vaccination. No severe CSF clinical signs were observed and no animals died although the challenge dose was 10(5)PDL(50) of a highly pathogenic CSFV strain. Noticeably, this response completely prevented CSFV infection in pigs when they were challenged under the same conditions 2 weeks after a single dose of the recombinant E2his vaccine formulation. A schedule consisting of a primary immunization with the same vaccine candidate, followed by a booster dose 2 weeks later induced a highly protective response against CSFV infection for as long as 9 months post-vaccination. These promising results demonstrate by far the feasibility of using the E2his-based vaccine in regional programs for preventing and controlling CSF.