AUTHOR=Yan Lina , Zhao Zhongxin , Xue Xianghong , Zheng Wenwen , Xu Tong , Liu Lele , Tian Li , Wang Xianwei , He Hongbin , Zheng Xuexing 

TITLE=A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.01070

DOI=10.3389/fmicb.2020.01070

ISSN=1664-302X

ABSTRACT=Rabies virus (RABV) and canine distemper virus (CDV) both are contagious antigens in global canine populations and cause server even lethal diseases in many mammals. In this study, a replication-deficient human adenovirus 5 (Ad5)-vectored vaccine stain, rAd5-G-H, co-expressing RABV glycoprotein (G) and CDV hemagglutinin (H) were constructed. The expression of RABV G and CDV H in Vero cells infected with rAd5-G-H was confirmed by indirect immunofluorescence assay (IFA). The rAd5-G-H demonstrated homogeneous icosahedral morphology similar to rAd5-GFP in electron microscope. A single dose of rAd5-G-H 108 GFU in mice or 109 GFU in foxes elicited rapid and robust neutralizing antibody responses against both RABV and CDV by intramuscular injection. Compared to the mock and rAd5-GFP inoculation group, dendritic cells and B cells were significantly recruited in inguinal lymph nodes in mice immunized rAd5-G-H by flow cytometry assays. Also, rAd5-G-H elicited both the Th1 and Th2 mediated cell immune responses to RABV and CDV in immunized mice, and all the mice survived of a lethal dose challenge of RABV with no clinical signs. In foxes, a single dose of rAd5-G-H 109 GFU also induced significant neutralizing antibody response against RABV and CDV in comparison of rAd5-GFP and mock groups. All foxes in rAd5-GFP and mock groups died, but all the foxes inoculated with rAd5-G-H were survived with no symptoms of disease after a lethal challenge of wild type CDV. These results suggested that rAd5-G-H served as a bivalent vaccine candidate with great potential against rabies and canine distemper in fur animals.