Oronasal vaccination with classical swine fever virus (CSFV) replicon particles with either partial or complete deletion of the E2 gene induces partial protection against lethal challenge with highly virulent CSFV

• Published in: Vaccine 2005-05, Vol.23 (25), p.3318-3328
• Main Authors: Maurer, Roland, Stettler, Peter, Ruggli, Nicolas, Hofmann, Martin A., Tratschin, Jon-Duri
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Administration, Oral; Amino acids; Animals; Applied microbiology; Atoms & subatomic particles; Biological and medical sciences; Cells, Cultured; Classical Swine Fever - immunology; Classical Swine Fever - prevention & control; Classical swine fever virus; Classical swine fever virus - immunology; Fundamental and applied biological sciences. Psychology; Gene Deletion; Genes; Hogs; Immune response; Injections, Intradermal; Microbiology; Miscellaneous; Oral vaccination; Pestivirus; Proteins; RNA, Viral - analysis; RNA, Viral - biosynthesis; Swine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Synthetic - immunology; Viral Envelope Proteins - genetics; Viral Vaccines - immunology; Virology; Virus replicon particles; Viruses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.01.076

A cDNA clone of the classical swine fever virus (CSFV) strain Alfort/187 [Ruggli N, Tratschin JD, Mittelholzer C, Hofmann MA. Nucleotide sequence of classical swine fever virus strain Alfort/187 and transcription of infectious RNA from stably cloned full-length cDNA. J Virol 1996;70(6):3478–87] was used to construct two E2 deletion mutants lacking either the complete E2 gene or, alternatively, a stretch of 204 nucleotides encoding 68 amino acids located in the C-terminal region of the E2 glycoprotein. The respective in vitro synthesized mutant RNAs replicated in SK-6 cells but no infectious virus was generated. Both replicons could be packaged into virus particles in SK-6 cells constitutively expressing E2 of CSFV. For the resulting CSF virus replicon particles (CSF-VRP) A187-E2del373 and A187-E2del68 titers of 10 6 and 10 7 TCID 50/ml, respectively, were obtained. Oronasal vaccination with 10 7 TCID 50 of either of the two CSF-VRP protected pigs against a challenge with a lethal dose of CSFV strain Eystrup. In contrast, after intradermal vaccination VRP A187-E2del68 but not VRP A187-E2del373 lacking the complete E2 gene induced a protective immune response. We conclude that E2-complemented CSF-VRP have the potential to be used as live-attenuated non-transmissible oral vaccines for pigs. In addition, our data suggest that E2 of CSFV is dispensable for the induction of mucosal but not of parenteral immunity.