The immune response to a recombinant Lactococcus lactis oral vaccine against foot-and-mouth disease virus in mice

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ORIGINAL RESEARCH PAPER

The immune response to a recombinant Lactococcus lactis oral vaccine against foot-and-mouth disease virus in mice Xinsheng Liu . Linlin Qi . Jianliang Lv . Zhongwang Zhang . Peng Zhou . Zhongyuan Ma . Yonglu Wang . Yongguang Zhang . Li Pan

Received: 12 November 2019 / Accepted: 24 April 2020 Ó Springer Nature B.V. 2020

Abstract Objective Development of an effective mucosal vaccine to induce specific immune responses against Foot-and-mouth disease virus (FMDV). Results For this purpose, the FMDV VP1 gene (SPVP1) was optimized and synthesized based on the codon bias of Lactococcus lactis (L. lactis), and then incorporated in the plasmid pNZ8148. L. lactis NZ9000 containing the pNZ8148-SPVP1 recombinant plasmid was used as an oral delivery vehicle to induce anti-FMDV mucosal and systemic immune responses in mice. After confirmation that the SPVP1 protein was expressed successfully in the recombinant L. latic, the mice were orally challenged with NZ9000pNZ8148, NZ9000-pNZ8148-SPVP1, phosphate-buffered saline as a mock infection group, or with

Xinsheng Liu and Linlin Qi have contributed equally to this study. X. Liu  L. Qi  J. Lv  Z. Zhang (&)  P. Zhou  Z. Ma  Y. Wang  Y. Zhang  L. Pan State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China e-mail: [email protected] Y. Zhang  L. Pan (&) Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, China e-mail: [email protected]

inactivated vaccine as a positive group. Mice immunized with NZ9000-pNZ8148-SPVP1 produced high levels of mucosal secretory IgA (sIgA), antigenspecific serum IgG, IgA, and neutralizing antibodies, and developed stronger cell-mediated immune reactions and significant T spleen lymphocyte proliferation. Furthermore, the recombinant group generated much higher levels of IFN-c, IL-2, IL-4, IL-5, and IL10 than the other groups. Conclusions Potent immune responses were successfully elicited in mice with FMDV VP1 delivered through L. lactis. Keywords Lactococcus lactis  Oral vaccine  Mucosal immunity  Foot-and-mouth disease virus  VP1 protein

Introduction Foot-and-mouth disease (FMD) is highly contagious and results in severe financial losses to the farming of cloven-hoofed animals. FMD virus (FMDV), grouped into the genus Aphthovirus of the family Picornaviridae, has seven different serologically distinct serotypes (O, A, C, Asia 1, SAT1, SAT2, and SAT3) with many antigenic variants of each. No cross-protective antibodies (Abs) can be detected in animals following infection or vaccination with other FMDV serotypes

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or subtypes, which has adversely affected the vaccination programs for the prevention of FMD (Jamal and Belsham 2013). FMDV is small non-enveloped virus with an icosahedral capsid symmetry including 60 copies,