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.