Recombinant canine distemper virus expressing virus-like particle VP2 protein of mink enteritis virus protects minks against lethal challenges of both viruses

Abstract

Canine distemper virus (CDV) and mink enteritis virus (MEV) are among the most devastating viruses in minks (Mustela vison). They often cause two fatal diseases-canine distemper (CD) and mink viral enteritis (MVE)-resulting in severe respiratory symptoms and acute enteritis in breeding minks, respectively. Here, using the attenuated CDV vaccine strain CDV3-CL (currently employed in breeding mink in China) as a backbone, we constructed a recombinant strain, rCDV3-mVP2, expressing the wild-type MEV capsid protein VP2. Notably, the VP2 protein expressed by this recombinant virus assembles into virus-like particles (VLPs) in Vero cells and exhibits hemagglutination activity. rCDV3-mVP2 exhibits genetic stability through at least 30 serial passages and replicates to titers comparable to the parental CDV3-CL strain in Vero cells. To evaluate its protective efficacy as a bivalent vaccine candidate, twenty weaned minks were immunized with rCDV3-mVP2 (10^4.0 TCID₅₀) and challenged with a highly virulent CDV strain (SD (14)7; n = 5 minks) or lethal MEV wild-type strain (LN-10; n = 5 minks) 3 weeks post-immunization. A single vaccination with rCDV3-mVP2 induced neutralizing antibodies (mean value = 43) against CDV and hemagglutination-inhibiting antibodies (mean value = 128) against MEV, conferring 100 % protection against lethal challenges of both viruses. Moreover, vaccination effectively alleviated lymphopenia, reduced virus shedding, and minimized tissue viral loads and pathological changes. These results suggest that rCDV-mVP2 is a suitable bivalent live vaccine against CDV and MEV for minks. IMPORTANCE: Canine distemper (CD) and mink viral enteritis (MVE), caused by canine distemper virus (CDV) and mink enteritis virus (MEV), respectively, are fatal diseases in minks, with significant impacts on the mink product industry. In this study, we employed reverse genetics to construct a recombinant CDV vaccine strain, rCDV3-mVP2, that expresses stably the MEV VP2 protein. Vaccination of weaned minks with rCDV3-mVP2 safely induced neutralizing antibody responses to both viruses, protecting minks from challenges with lethal CDV and MEV. This is the first study to demonstrate that recombinant CDV can be serve as a bivalent live vaccine for MVE and CD in animals.

Keywords: Bivalent live vaccine; Canine distemper virus; Capsid protein 2; Mink; Mink enteritis virus; Virus-like particles.