Immunogenicity and protective efficacy of a novel bacterium-like particle-based vaccine displaying canine distemper virus antigens in mice and dogs.

Canine distemper virus (CDV) poses a severe threat to both domesticated and wild animals, including multiple carnivores. With the continued expansion of its host range, there is an urgent need for the development of a safer and more effective vaccine. In this study, we developed subunit vaccines based on a bacterium-like particle (BLP) delivery platform containing BLPs-F and BLPs-H, which display the CDV F and H glycoprotein antigens, respectively, using the antigen-protein anchor fusions produced by a recombinant baculovirus insect cell expression system. The combination of BLPs-F and BLPs-H (CDV-BLPs), formulated with colloidal manganese salt [Mn jelly (MnJ)] adjuvant, triggered robust CDV-specific antibody responses and a substantial increase in the number of interferon gamma (IFN-γ)-secreting CD4+ and CD8+ T cells in mice. Dogs immunized intramuscularly with this vaccine not only produced CDV-specific IgG but also displayed elevated concentrations of IFN-γ and interleukin 6 in their serum, along with an increase of the CD3+CD4+ and CD3+CD8+ T cell subsets. Consequently, this heightened immune response provided effective protection against disease development and reduced viral shedding levels following challenge with a virulent strain. These findings suggest that this BLP-based subunit vaccine has the potential to become a novel canine distemper vaccine. IMPORTANCE: Many sensitive species require a safe and effective distemper vaccine. Non-replicating vaccines are preferred. We constructed subunit particles displaying canine distemper virus (CDV) antigens based on a bacterium-like particle (BLP) delivery platform. The CDV-BLPs formulated with theMn jelly adjuvant induced robust humoral and cell-mediated immune responses to CDV in mice and dogs, thereby providing effective protection against a virulent virus challenge. This work is an important step in developing a CDV subunit vaccine.

Protection against genotype VII Newcastle disease virus by a mucosal subunit vaccination based on bacterium-like particles bearing the F or HN antigen.

Genotype VII Newcastle disease viruses (NDV) are still epidemic in many countries in chicken and waterfowl despite intensive vaccination with conventional live and inactivated vaccines. Here, we developed an effective mucosal subunit vaccine based on a bacterium-like particles (BLPs) delivery platform derived from Lactococcus lactis. The NDV protective antigen F or HN fused protein anchor (PA) was expressed by recombinant baculovirus and loaded on the surface of BLPs, resulting in BLPs-F and BLPs-HN, respectively. Efficient uptake of BLPs-F/HN by antigen-presenting cells activated the innate immune system depending mainly on the combination of chicken TLR2 type 1 (chTLR2t1) and chicken TLR1 type 1 (chTLR1t1) was observed. Delivered intranasally, BLPs-F, BLPs-HN, or BLPs-F/HN (a mixture containing equal amounts of BLPs-F and BLPs-HN) elicited robust local NDV-specific SIgA in the trachea as well as systemic neutralizing antibody and a mixed Th1/Th2 immune response in chickens. Notably, BLPs-F/HN provided as high as 90 % protection rate against intranasal challenge with a lethal dose of virulent genotype VII NDV NA-1 strain. These data indicate that this BLP-based subunit vaccine has the potential to be a novel mucosal vaccine against genotype VII NDV infection.