Abstract
Live vector-based vaccine is a modern approach to overcome the drawbacks of inactivated foot-and-mouth disease (FMD) vaccines such as improper inactivation during manufacture. Listeria monocytogenes (LM), an intracellular microorganism with immune-stimulatory properties, is appropriate to be utilized as a live bacterial vaccine vector. FMDV-VP1 protein has the capability to induce both cellular and humoral immune responses since it is considered the most immunogenic part of FMDV capsid and has the most of antigenic sites for viral neutralization. The codon-optimized vp1 gene was ligated to the integrative pCW702 plasmid to construct the target cassette. The antigen cassette was integrated successfully into the chromosome of mutant LM strain via homologous recombination for more stability to generate a candidate vaccine strain LM△actAplcB-vp1. Safety evaluation of recombinant LM△actAplcB-vp1 revealed it could be eliminated from the internal organs within 3 days as a safe candidate vaccine. Mice groups were immunized I.V. twice with the recombinant LM△actAplcB-vp1 at an interval of 2 weeks. Antigen-specific IgG antibodies and the level of CD4+- and CD8+-specific secreted cytokines were estimated to evaluate the immunogenicity of the candidate vaccine. The rapid onset immune response was detected, strong IgG humoral immune response within 14 days post immunization and augmented again after the booster dose. Cellular immunity data after 9 days post the prime dose indicated elevation in CD4+ and CD8+ secreted cytokine level with another elevation after the booster dose. This is the first report to explain the ability of attenuated mutant LM to be a promising live vector for FMDV vaccine.
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References
Bautista EM, Ferman GS, Golde WT (2003) Induction of lymphopenia and inhibition of T cell function during acute infection of swine with Foot and mouth disease virus (FMDV). Vet Immunol Immunopathol 92(1–2):61–73
Bhunia AK (1997) Antibodies to Listeria monocytogenes. Crit Rev Microbiol 23(2):77–107
Bierne H, Milohanic E, Kortebi M (2018) To be cytosolic or vacuolar: the double life of Listeria monocytogenes. Front Cell Infect Microbiol 8:136
Cao Y, Li D, Fu Y, Bai Q, Chen Y, Bai X, Jing Z, Sun P, Bao H, Li P (2017) Rational design and efficacy of a multi-epitope recombinant protein vaccine against Foot-and-mouth disease virus serotype A in pigs. Antivir Res 140:133–141
Clavijo A, Wright P, Kitching P (2004) Developments in diagnostic techniques for differentiating infection from vaccination in Foot-and-mouth disease. Vet J 167(1):9–22
Conlan JW (1996) Early pathogenesis of Listeria monocytogenes infection in the mouse spleen. J Med Microbiol 44(4):295–302
Conlan JW (1999) Early host-pathogen interactions in the liver and spleen during systemic murine Listeriosis: an overview. Immunobiology 201(2):178–187
Cousens LP, Wing EJ (2000) Innate defenses in the liver during Listeria infection. Immunol Rev 174:150–159
Doel T (2003) FMD vaccines. Virus Res 91:81–99
Du J, Chang H, Cong G, Shao J, Lin T, Shang Y, Liu Z, Liu X, Cai X, Xie Q (2007) Complete nucleotide sequence of a Chinese serotype Asia1 vaccine strain of Foot-and-mouth disease virus. Virus Genes 35(3):635–642
Dussurget O, Pizarro-Cerda J, Cossart P (2004) Molecular determinants of Listeria monocytogenes virulence. Annu Rev Microbiol 58:587–610
Edelson BT, Cossart P, Unanue ER (1999) Cutting edge: paradigm revisited: antibody provides resistance to Listeria infection. J Immunol 163(8):4087–4090
Gerner W, Hammer SE, Wiesmüller K-H, Saalmüller A (2009) Identification of major histocompatibility complex restriction and anchor residues of Foot-and-mouth disease virus-derived bovine T-cell epitopes. J Virol 83(9):4039–4050
Goldfine H, Shen H (2007) Listeria monocytogenes: pathogenesis and host response. Springer
Gründling A, Gonzalez MD, Higgins DE (2003) Requirement of the Listeria monocytogenes broad-range phospholipase PC-PLC during infection of human epithelial cells. J Bacteriol 185(21):6295–6307
Gu P, Yang F, Su T, Wang Q, Liang Q, Qi Q (2015) A rapid and reliable strategy for chromosomal integration of gene (s) with multiple copies. Sci Rep 5:9684
Guzman E, Taylor G, Charleston B, Skinner MA, Ellis SA (2008) An MHC-restricted CD8+ T-cell response is induced in cattle by Foot-and-mouth disease virus (FMDV) infection and also following vaccination with inactivated FMDV. J Gen Virol 89(3):667–675
Heath WR, Carbone FR (2001) Cross-presentation, dendritic cells, tolerance and immunity. Annu Rev Immunol 19(1):47–64
Jamal SM, Belsham GJ (2013) Foot-and-mouth disease: past, present and future. BMC Vet Res 44(1):116
James AD, Rushton J (2002) The economics of Foot and mouth disease. Rev Sci Tech 21(3):637–641
Juleff N, Windsor M, Lefevre EA, Gubbins S, Hamblin P, Reid E, McLaughlin K, Beverley PC, Morrison IW, Charleston B (2009) Foot-and-mouth disease virus can induce a specific and rapid CD4+ T-cell-independent neutralizing and isotype class-switched antibody response in naive cattle. J Virol 83(8):3626–3636
Lauer P, Chow MYN, Loessner MJ, Portnoy DA, Calendar R (2002) Construction, characterization, and use of two Listeria monocytogenes site-specific phage integration vectors. J Bacteriol 184(15):4177–4186
Li W, Joshi MD, Singhania S, Ramsey KH, Murthy AK (2014) Peptide vaccine: progress and challenges. Vaccine 2(3):515–536
Li Y-G, Tian F-L, Gao F-S, Tang X-S, Xia C (2007) Immune responses generated by Lactobacillus as a carrier in DNA immunization against Foot-and-mouth disease virus. Vaccine 25(5):902–911
Nascimento I, Leite L (2012) Recombinant vaccines and the development of new vaccine strategies. Braz J Med Biol Res 45(12):1102–1111
Peralta A, Maroniche GA, Alfonso V, Molinari P, Taboga O (2013) VP1 protein of Foot-and-mouth disease virus (FMDV) impairs baculovirus surface display. Virus Res 175(1):87–90
Perry B, Rich K (2007) Poverty impacts of Foot-and-mouth disease and the poverty reduction implications of its control. View point Vet Rec Open (UK)
Ramakrishnan MA (2016) Determination of 50% endpoint titer using a simple formula. World J Virol 5(2):85–86
Saklani-Jusforgues H, Fontan E, Soussi N, Milon G, Goossens PL (2003) Enteral immunization with attenuated recombinant Listeria monocytogenes as a live vaccine vector: organ-dependent dynamics of CD4 T lymphocytes reactive to a Leishmania major tracer epitope. Infect Immun 71(3):1083–1090
Sanz-Parra A, Jimenez-Clavero M, Garcıa-Briones M, Blanco E, Sobrino F, Ley V (1999) Recombinant viruses expressing the Foot-and-mouth disease virus capsid precursor polypeptide (P1) induce cellular but not humoral antiviral immunity and partial protection in pigs. Virology 259(1):129–134
Scortti M, Monzó HJ, Lacharme-Lora L, Lewis DA, Vázquez-Boland JA (2007) The PrfA virulence regulon. Microbes Infect 9(10):1196–1207
Shetron-Rama LM, Marquis H, Bouwer HA, Freitag NE (2002) Intracellular induction of Listeria monocytogenes actA expression. Infect Immun 70(3):1087–1096
Szalay G, Hess J, Kaufmann SH (1994) Presentation of Listeria monocytogenes antigens by major histocompatibility complex class I molecules to CD8 cytotoxic T lymphocytes independent of listeriolysin secretion and virulence. Eur J Immunol 24(7):1471–1477
Toledo-Arana A, Dussurget O, Nikitas G, Sesto N, Guet-Revillet H, Balestrino D, Loh E, Gripenland J, Tiensuu T, Vaitkevicius K (2009) The Listeria transcriptional landscape from saprophytism to virulence. Nature 459(7249):950–956
Wang C, Zhang F, Yang J, Khanniche A, Shen H (2014) Expression of Porcine respiratory and reproductive syndrome virus membrane-associated proteins in Listeria ivanovii via a genome site-specific integration and expression system. J Mol Microbiol 24(3):191–195
Wong HT, Cheng SCS, Chan EWC, Sheng ZT, Yan WY, Zheng ZX, Xie Y (2000) Plasmids encoding Foot-andmouth disease virus VP1 epitopes elicited immune responses in mice and swine and protected swine against viral infection. Virology 278(1):27–35
Acknowledgments
Thanks for the research platform provided by the Research Centre for Public Health and Preventive Medicine, West China School of Public Health, West China Teaching Hospital, Sichuan University.
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This study was financially supported by the National Natural Science Foundation of China under Scientific Research Project (No. 31570924).
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Chuan Wang, Mahdy S.E, and Xiaofang Pei designed the study, conceptualized and drafted the manuscript, designed and conducted the data collection, planned the data analysis, wrote the manuscript, and revised the manuscript; Sijing Liu, Lin Su, Xiang Zhang, and Hao-tai Chen analyzed the data collection.
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All Female C57BL/6J mice of 6–8 weeks old were purchased from the Institute of Laboratory Animals of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital. Mice were kept under restricted hygienic conditions during the experiments at the Animal Centre of School of Public Health at Sichuan University. Mouse experiments were performed according to the guidelines of the Animal Care and Use Committee of Sichuan University.
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Mahdy, S.E., Liu, S., Su, L. et al. Expression of the VP1 protein of FMDV integrated chromosomally with mutant Listeria monocytogenes strain induced both humoral and cellular immune responses. Appl Microbiol Biotechnol 103, 1919–1929 (2019). https://doi.org/10.1007/s00253-018-09605-x
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DOI: https://doi.org/10.1007/s00253-018-09605-x