Construction and evaluation of an adenovirus/alphavirus replicon chimeric vectored vaccine against classical swine fever (#82)
Classical swine fever (CSF), which is caused by classical swine fever virus (CSFV), is one of the most devastating epizootic diseases of pigs worldwide. Efficacious and safe attenuated vaccines have played a key role in CSF control, but they have some disadvantages, for example, they are often contaminated with bovine viral diarrhea virus (BVDV) and do not allow differentiation of infected from vaccinated animals (DIVA principle).
Previously, we showed that prime-boost immunization using an adenovirus-vectored vaccine rAdV-E2 and an alphavirus replicon-vectored DNA vaccine pSFV1CS-E2, but none of the two vaccines alone, induced complete protection from virulent challenge [1-3]. In this study, we used the adenoviral vector to deliver the alphavirus replicon vector and constructed an adenovirus/alphavirus replicon chimeric virus expressing the E2 protein of CSFV. Pigs immunized with rAdV-SFV-E2 (n = 5) developed robust humoral and cell-mediated responses to CSFV and were completely protected from subsequent lethal CSFV infection clinically and virologically. The level of immunity and protection induced by rAdV-SFV-E2 was comparable to that provided by the currently used live attenuated vaccine, C-strain. By contrast, both the conventional alphavirus replicon-vectored vaccine pSFV1CS-E2 and conventional adenovirus-vectored vaccine rAdV-E2 provided incomplete protection.
We further evaluated the safety and efficacy of the chimeric virus with respect to different immunization times and doses, pre-existing antibodies to the adenovirus vector, maternal antibody interference and combination immunization with PRV vaccine. The results showed that the minimal immunization dose is 6.25×105 TCID50 in pigs. A single immunization provided complete protection against lethal CSFV challenge, though specific neutralizing antibodies were undetectable before challenge. The chimeric virus can overcome CSF maternal antibody interference and immunization with the chimeric virus did not affect re-immunization of adenovirus-vectored vaccines. When the chimeric virus was co-administered with pseudorabies vaccine, all immunized pigs developed high-level specific antibodies against CSFV and PRV comparable to either vaccine administered alone.
The chimeric vector-based vaccine represents the first gene-based vaccine that is able to confer sterile immunity and complete protection against CSFV.
- Li N, Qiu HJ*, Zhao JJ, Li Y, Wang MJ, Lu BW, Han CG, Hou Q, Wang ZH, Gao H, Peng WP, Li GX, Zhu QH, Tong GZ. A Semliki Forest virus replicon vectored DNA vaccine expressing the E2 glycoprotein of classical swine fever virus protects pigs from lethal challenge. Vaccine. 2007 Apr 12;25(15):2907-12.
- Sun Y, Liu DF, Wang YF, Liang BB, Cheng D, Li N, Qi QF, Zhu QH, Qiu HJ*. Generation and efficacy evaluation of a recombinant adenovirus expressing the E2 protein of classical swine fever virus. Res Vet Sci. 2010 Feb;88(1):77-82.
- Sun Y, Li N, Li HY, Li M, Qiu HJ*. Enhanced immunity against classical swine fever in pigs induced by prime-boost immunization using an alphavirus replicon-vectored DNA vaccine and a recombinant adenovirus. Vet Immunol Immunopathol. 2010;137(1-2):20-7.