Construction and evaluation of recombinant Lactobacillus plantarum NC8 delivering one single or two copies of G protein fused with a DC-targeting peptide (DCpep) as novel oral rabies vaccine

Abstract

Rabies remains an important public health threat in most developing countries. To develop a more effective and safe oral vaccine against rabies, we constructed recombinant Lactobacillus plantarum NC8 carrying one or two copies of the G gene with a dendritic cell-targeting peptide (DCpep) fused at the C-terminal designated NC8-pSIP409-sRVG or NC8-pSIP409-dRVG, respectively. The immunogenicity and protective efficacy of these recombinant Lactobacillus plantarum against RABV were evaluated by oral administration in a mouse model. The results showed that recombinant NC8-pSIP409-dRVG possessed more G protein, resulting in more functional maturation of DCs. After three cycle of oral immunization, NC8-pSIP409-dRVG induced significantly higher levels of specific IgG antibody and mixed Th1/Th2 with a strong Th1-biasd immune response in mice. Most importantly, although the titers of RABV neutralizing antibody (VNA) were below the threshold of 0.5 IU/mL, the NC8-pSIP409-dRVG could protect 60 % of inoculated mice against lethal RABV challenge. These data reveal that recombinant NC8-pSIP409-dRVG may be a novel and promising oral vaccine candidate to prevent and control of animal rabies.