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Volume 9
Issue 2
10.3390/vaccines9020122
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Article

Optimized Detoxification of a Live Attenuated Vaccine Strain (SG9R) to Improve Vaccine Strategy against Fowl Typhoid

by
Nam-Hyung Kim
1,2,
Dae-Sung Ko
1,2,
Eun-Jin Ha
1,2,
Sunmin Ahn
1,2,
Kang-Seuk Choi
2,3,* and
Hyuk-Joon Kwon
1,2,4,*
1
Laboratory of Poultry Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
2
Research Institute for Veterinary Science, College of Veterinary Medicine, BK21 for Veterinary Science, Seoul 08826, Korea
3
Laboratory of Avian Diseases, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
4
Farm Animal Clinical Training and Research Center (FACTRC), GBST, Seoul National University, Seoul 08826, Korea
*
Authors to whom correspondence should be addressed.
Vaccines 2021, 9(2), 122; https://doi.org/10.3390/vaccines9020122
Submission received: 14 January 2021 / Revised: 29 January 2021 / Accepted: 1 February 2021 / Published: 3 February 2021
(This article belongs to the Special Issue Analysis and Modification of Existing Vaccines for the Development of Next-Generation Vaccines)
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Abstract

The live attenuated vaccine strain, SG9R, has been used against fowl typhoid worldwide, but it can revert to the pathogenic smooth strain owing to single nucleotide changes such as nonsense mutations in the rfaJ gene. As SG9R possesses an intact Salmonella plasmid with virulence genes, it exhibits dormant pathogenicity and can cause fowl typhoid in young chicks and stressed or immunocompromised brown egg-laying hens. To tackle these issues, we knocked out the rfaJ gene of SG9R (named Safe-9R) to eliminate the reversion risk and generated detoxified strains of Safe-9R by knocking out lpxL, lpxM, pagP, and phoP/phoQ genes to attenuate the virulence. Among the knockout strains, live ΔlpxL- (Dtx-9RL) and ΔlpxM-9R (Dtx-9RM) strains induced remarkably less expression of inflammatory cytokines in chicken macrophage cells, and oil emulsion (OE) Dtx-9RL did not cause body weight loss in chicks. Live Dtx-9RM exhibited efficacy against field strain challenge in one week without any bacterial re-isolation, while the un-detoxified strains showed the development of severe liver lesions and re-isolation of challenged strains. Thus, SG9R was optimally detoxified by knockout of lpxL and lpxM, and Dtx-9RL and Dtx-9RM might be applicable as OE and live vaccines, respectively, to prevent fowl typhoid irrespective of the age of chickens.
Keywords: Salmonella enterica serovar Gallinarum biovar Gallinarum; SG9R; detoxification; lipid A; vaccines; pro-inflammatory cytokines Salmonella enterica serovar Gallinarum biovar Gallinarum; SG9R; detoxification; lipid A; vaccines; pro-inflammatory cytokines

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MDPI and ACS Style

Kim, N.-H.; Ko, D.-S.; Ha, E.-J.; Ahn, S.; Choi, K.-S.; Kwon, H.-J. Optimized Detoxification of a Live Attenuated Vaccine Strain (SG9R) to Improve Vaccine Strategy against Fowl Typhoid. Vaccines 2021, 9, 122. https://doi.org/10.3390/vaccines9020122

AMA Style

Kim N-H, Ko D-S, Ha E-J, Ahn S, Choi K-S, Kwon H-J. Optimized Detoxification of a Live Attenuated Vaccine Strain (SG9R) to Improve Vaccine Strategy against Fowl Typhoid. Vaccines. 2021; 9(2):122. https://doi.org/10.3390/vaccines9020122

Chicago/Turabian Style

Kim, Nam-Hyung, Dae-Sung Ko, Eun-Jin Ha, Sunmin Ahn, Kang-Seuk Choi, and Hyuk-Joon Kwon. 2021. "Optimized Detoxification of a Live Attenuated Vaccine Strain (SG9R) to Improve Vaccine Strategy against Fowl Typhoid" Vaccines 9, no. 2: 122. https://doi.org/10.3390/vaccines9020122

APA Style

Kim, N.-H., Ko, D.-S., Ha, E.-J., Ahn, S., Choi, K.-S., & Kwon, H.-J. (2021). Optimized Detoxification of a Live Attenuated Vaccine Strain (SG9R) to Improve Vaccine Strategy against Fowl Typhoid. Vaccines, 9(2), 122. https://doi.org/10.3390/vaccines9020122

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