Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Rational Design and Generation of the ShigETEC Vaccine
3.2. Phenotypic Characterization of ShigETEC
3.2.1. ShigETEC Expresses Rough Lipopolysaccharide
3.2.2. ShigETEC Is Non-Invasive and Avirulent
3.2.3. ShigETEC Expresses Detoxified ETEC Toxin Antigens
3.3. ShigETEC Vaccination Provides Serotype-Independent Protection against Shigella Challenge
3.4. ShigETEC Vaccination Induces Systemic and Mucosal Antibody Responses against Shigellae and ETEC Toxins
3.5. ShigETEC Vaccination Induces Neutralizing Anti-ETEC Toxin Antibodies
4. Discussion
5. Conclusions
6. Patents
Author Contributions
Funding
Conflicts of Interest
References
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Genetic Manipulation | Location of wt Gene | Phenotypic Change |
---|---|---|
Deletions: | ||
rfbF | chromosome | Rough, lacking LPS O-antigen |
ipaBC | invasion plasmid | Non-invasive |
setBA | chromosome | ShET-1 and Pic defective |
infA | chromosome | Trans-positioned to the invasion plasmid for plasmid stabilization |
Insertions: | ||
infA-3xLTB-STN12S | n.a. | Stable invasion plasmid, expression of ETEC toxoid antigens |
Experiment #1 | Experiment #2 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Wild-Type | ShigETEC | Wild-Type | ShigETEC | |||||||||||||
106 | 107 | 108 | 109 | 106 | 107 | 108 | 109 | 106 | 107 | 108 | 109 | 106 | 107 | 108 | 109 | |
Day 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
Day 2 | 0 | 1 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
Day 3 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
Day 4 | 0 | 2 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 |
Day 5 | 0 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 |
Day 6 | 0 | 4 | 4 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 4 | 0 | 0 | 0 | 0 |
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Harutyunyan, S.; Neuhauser, I.; Mayer, A.; Aichinger, M.; Szijártó, V.; Nagy, G.; Nagy, E.; Girardi, P.; Malinoski, F.J.; Henics, T. Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC. Vaccines 2020, 8, 689. https://doi.org/10.3390/vaccines8040689
Harutyunyan S, Neuhauser I, Mayer A, Aichinger M, Szijártó V, Nagy G, Nagy E, Girardi P, Malinoski FJ, Henics T. Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC. Vaccines. 2020; 8(4):689. https://doi.org/10.3390/vaccines8040689
Chicago/Turabian StyleHarutyunyan, Shushan, Irene Neuhauser, Alexandra Mayer, Michael Aichinger, Valéria Szijártó, Gábor Nagy, Eszter Nagy, Petra Girardi, Frank J. Malinoski, and Tamás Henics. 2020. "Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC" Vaccines 8, no. 4: 689. https://doi.org/10.3390/vaccines8040689
APA StyleHarutyunyan, S., Neuhauser, I., Mayer, A., Aichinger, M., Szijártó, V., Nagy, G., Nagy, E., Girardi, P., Malinoski, F. J., & Henics, T. (2020). Characterization of ShigETEC, a Novel Live Attenuated Combined Vaccine against Shigellae and ETEC. Vaccines, 8(4), 689. https://doi.org/10.3390/vaccines8040689