Development of a neutralizing mouse-pig chimeric antibody with therapeutic potential against Haemophilus parasuis in Pichia pastoris.
Haemophilus parasuis is one of the most important bacterial diseases of pigs worldwide. The lack of a vaccine against a broad spectrum of strains and the limitation of antimicrobial susceptibility hamper the control of disease. In this study, we cloned the constant regions of gamma heavy chains and kappa light chain of pig lymphocytes in frame with the variable regions of heavy and light chains of mouse monoclonal antibody 1D8, which reacts with all 15 serotypes of H. parasuis and has neutralizing activity. The constructed mouse-pig chimeric antibody was expressed in Pichia pastoris. Results demonstrated that the expressed chimeric antibody inhibited the growth of H. parasuis in vitro. Furthermore, the experiments in mice showed that chimeric antibody increased survival rate of the mice compared with that of the control group (P < 0.05). Importantly, the chimeric antibody partially protected piglets against H. parasuis infection according to the clinical lesion scores and PCR results of H. parasuis in the tissues from piglets of the chimeric antibody-inoculated group and the PBS group. In summary, our results demonstrated that the mouse-pig chimeric antibody could be a therapeutic candidate to prevent the H. parasuis infection and control the prevalence of disease.
State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Zheng
Z
Chai
Fang
F
Fu
Fucheng
F
Jiang
Huabin
H
Tian
Zhuo
Z
Wang
Nan
N
Zheng
Xueyun
X
Zhang
Xiangling
X
Wang
Xi
X
Li
D000818:Animals; D000907:Antibodies, Bacterial / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D057134:Antibodies, Neutralizing / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D015870:Gene Expression; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology / Q000662:veterinary*; D044137:Haemophilus parasuis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010843:Pichia / Q000235:genetics* / Q000378:metabolism; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D013552:Swine; D013553:Swine Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000517:prevention & control
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D011993:Recombinant Fusion Proteins
Haemophilus parasuis; Pichia pastoris; chimeric antibody; immunotherapy