An E2 glycoprotein-based recombinant subunit vaccine confers protective immunity against classical swine fever virus...

CSFV is a highly contagious disease threatening global pig production. Conventional live vaccines protect effectively but prevent serological differentiation between infected and vaccinated animals-undermining surveillance and eradication efforts. Therefore, it is crucial to develop a new generation of safe and effective vaccines. This study targeted the CSFV E2 glycoprotein, rationally optimized its amino acid sequence, expressed the recombinant protein at high yield in CHO cells, and demonstrated its immunogenicity and complete protection against virulent CSFV challenge. The E2 subunit vaccine was safe in piglets, with no inflammation, fever, or mortality during immunization. The E2 subunit vaccine induces high titers of CSFV-specific and neutralizing antibodies, and its immune protection efficacy is no less than that of commercially available vaccines. In the piglet challenge test, no CSFV was detected in oral, nasal, or rectal swabs or peripheral blood from immunized piglets. No CSFV was detected in the spleen, lymph nodes, or tonsils at autopsy. No CSFV-specific lesions were found on histopathology. All immunized piglets survived. These results demonstrate that piglets vaccinated with the E2 subunit vaccine were completely protected against lethal CSFV challenge. The successful development of a recombinant E2 subunit vaccine against CSFV represents a strategic advance toward sustainable control and eventual eradication of the disease.