Regulated delayed attenuation improves vaccine efficacy in preventing infection from avian pathogenic Escherichia coli O(78) and Salmonella typhimurium.

Affiliation

Han Y(1), Luo P(1), Chen Y(1), Xu J(1), Sun J(1), Guan C(1), Wang P(1), Chen M(1), Zhang X(1), Zhu Y(1), Zhu T(1), Zhai R(1), Cheng C(2), Song H(3).
Author information:
(1)China-Australian Joint Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology, College of Veterinary Medicine of Zhejiang A&F University, Lin'an, China.
(2)China-Australian Joint Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology, College of Veterinary Medicine of Zhejiang A&F University, Lin'an, China. Electronic address: [Email]
(3)China-Australian Joint Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology, College of Veterinary Medicine of Zhejiang A&F University, Lin'an, China. Electronic address: [Email]

Abstract

Avian pathogenic Escherichia coli (APEC) O78 and Salmonella typhimurium (S. Typhimurium) are two leading bacterial pathogens that cause significant economic loss in the poultry industry. O-antigen is an important immunogen of these two bacteria to induce host protective immune responses during infection. To develop a bivalent vaccine against APEC O78 and S. Typhimurium, the attenuated Salmonella ST01 (Δasd ΔrfbP Δcrp) was genetically constructed to deliver APEC O78 O-antigen polysaccharide (OPS), which stably expresses OPS with asd+ balanced-lethal system in vitro and in vivo. After oral immunization, the recombinant attenuated Salmonella vaccine (RASV) strain ST01 (pSS26-O78) provided insufficient protection against the APEC O78 challenge. Therefore, the regulated delayed attenuation strain ST02 (Δasd ΔrfbP ΔPcrp::TTaraC PBADcrp) was further constructed by regulating cyclic AMP receptor protein (crp) with araC PBAD cassette to better present the heterologous O-antigen to the host immune system. The innovative recombinant strain ST02 (pSS26-O78) stimulated robust antibody responses against APEC O78 and S. Typhimurium OPS, with serum titers over 1:800 for both IgG and IgA, thereby providing the complement-mediated bactericidal activity and stronger protection against APEC O78 and S. Typhimurium infection. Collectively, this study demonstrates a biologically-conjugated polysaccharide vaccine candidate that can enhance homologous protection against APEC O78 and S. Typhimurium.