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Efficient Expression of an Alzheimer’s Disease Vaccine Candidate in the Microalga Schizochytrium sp. Using the Algevir System

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Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disease, where β-amyloid (Aβ) plays a key role in forming conglomerated senile plaques. The receptor of advanced glycation end products (RAGE) is considered a therapeutic target since it transports Aβ into the central nervous system, favoring the pathology progression. Due to the lack of effective therapies for AD, several therapeutic approaches are under development, being vaccines considered a promising alternative. Herein, the use of the Algevir system was explored to produce in the Schizochytrium sp. microalga the LTB:RAGE vaccine candidate. Algevir relies in an inducible geminiviral vector and led to yields of up to 380 µg LTB:RAGE/g fresh weight biomass at 48-h post-induction. The Schizochytrium-produced LTB:RAGE vaccine retained its antigenic activity and was highly stable up to temperatures of 60 °C. These data demonstrate the potential of Schizochytrium sp. as a platform for high production of thermostable recombinant antigens useful for vaccination against AD.

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References

  1. Martí, M. J., Tolosa, E., & Campdelacreu, J. (2003). Clinical overview of the synucleinopathies. Movement Disorders, 18(S6), 21–27.

    Article  Google Scholar 

  2. Youm, J. W., Jeon, J. H., Kim, H., Kim, Y. H., Ko, K., Joung, H., et al. (2008). Transgenic tomatoes expressing human beta-amyloid for use as a vaccine against Alzheimer’s disease. Biotechnology Letters, 30, 1839–1845.

    Article  CAS  Google Scholar 

  3. Anand, R., Gill, K. D., & Mahdi, A. A. (2014). Therapeutics of Alzheimer’s disease: Past, present and future. Neuropharmacology, 76, 27–50.

    Article  CAS  Google Scholar 

  4. Rosales-Mendoza, S., Rubio-Infante, N., Zarazúa, S., Govea-Alonso, D., Martel-Gallegos, G., & Moreno-Fierros, L. (2014). Plant-based vaccines for Alzheimer’s disease: An overview. Expert Review of Vaccines, 13, 429–441.

    Article  CAS  Google Scholar 

  5. Liu, B., Frost, J. L., Sun, J., Fu, H., Grimes, S., Blackburn, P., et al. (2013). MER5101, a novel Aβ1-15: DT conjugate vaccine, generates a robust anti-Aβ antibody response and attenuates Aβ pathology and cognitive deficits in APPswe/PS1ΔE9 transgenic mice. The Journal of Neuroscience, 33, 7027–7037.

    Article  CAS  Google Scholar 

  6. Arevalo-Villalobos, J. I., Govea-Alonso, D. O., Monreal-Escalante, E., Zarazúa, S., & Rosales-Mendoza, S. (2017). LTB-Syn: A recombinant immunogen for the development of plant-made vaccines against synucleinopathies. Planta, 245(6), 1231–1239.

    Article  CAS  Google Scholar 

  7. Yan, S. S., Chen, D., Yan, S., Guo, L., & Chen, J. X. (2012). RAGE is a key cellular target for Aβ-induced perturbation in Alzheimer’s disease. Frontiers in Bioscience (Scholar Edition), 4, 240.

    Article  Google Scholar 

  8. Schmidt, A. M., Yan, S. D., Yan, S. F., & Stern, D. M. (2000). The biology of the receptor for advanced glycation end products and its ligands. Biochimica et Biophysica Acta, 1498(2–3), 99–111.

    Article  CAS  Google Scholar 

  9. Webster, S. J., Mruthinti, S., Hill, W. D., Buccafusco, J. J., & Terry, A. V., Jr. (2012). An aqueous orally active vaccine targeted against a RAGE/AB complex as a novel therapeutic for Alzheimer’s disease. NeuroMolecular Medicine, 14, 119–130.

    Article  CAS  Google Scholar 

  10. Youm, J. W., Kim, H., Han, J. H., Jang, C. H., Ha, H. J., Mook-Jung, I., et al. (2005). Transgenic potato expressing Aβ reduce Aβ burden in Alzheimer’s disease mouse model. FEBS Letters, 579, 6737–6744.

    Article  CAS  Google Scholar 

  11. Yokoyama, R., & Honda, D. (2007). Taxonomic rearrangement of the genus Schizochytrium sensu lato based on morphology, chemotaxonomic characteristics, and 18S rRNA gene phylogeny (Thraustochytriaceae, Labyrinthulomycetes): emendation for Schizochytrium and erection of Aurantiochytrium and Oblongichytrium. Gen Nov Mycoscience, 48(4), 199–211.

    Article  CAS  Google Scholar 

  12. Meale, S. J., Chaves, A. V., He, M. L., & McAllister, T. A. (2014). Dose—response of supplementing marine algae (Schizochytrium sp.) on production performance, fatty acid profiles, and wool parameters of growing lambs. Journal of Animal Science, 92(5), 2202–2213.

    Article  CAS  Google Scholar 

  13. Ren, L. J., Ji, X. J., Huang, H., Qu, L., Feng, Y., Tong, Q. Q., et al. (2010). Development of a stepwise aeration control strategy for efficient docosahexaenoic acid production by Schizochytrium sp. Applied Microbiology and Biotechnology, 87(5), 1649–1656.

    Article  CAS  Google Scholar 

  14. Bayne, A. C., Boltz, D., Owen, C., Betz, Y., Maia, G., Azadi, P., et al. (2013). Vaccination against influenza with recombinant hemagglutinin expressed by Schizochytrium sp. confers protective immunity. PLoS ONE, 8(4), e61790.

    Article  CAS  Google Scholar 

  15. Bañuelos-Hernández, B., Monreal-Escalante, E., González-Ortega, O., Angulo, C., & Rosales-Mendoza, S. (2017). Algevir: an expression system for microalgae based on viral vectors. Frontiers on Microbiology, 8, 1100.

    Article  Google Scholar 

  16. Romero-Maldonado, A., Monreal-Escalante, E., & Rosales-Mendoza, S. (2016). Expression in plants of two new antigens with implications in Alzheimer’s disease immunotherapy. Plant Cell, Tissue and Organ Culture (PCTOC). https://doi.org/10.1007/s11240-016-0990-9.

    Google Scholar 

  17. Neper, M., Schmidt, A. M., Brett, J., Yan, S. D., Wang, F., Pan, Y. C., et al. (1992). Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. Journal of Biological Chemistry, 267(21), 14998–15004.

    Google Scholar 

  18. Cangelosi, G. A., Best, E. A., Martinetti, G., & Nester, E. W. (1991). Genetic analysis of Agrobacterium. Methods in Enzymology, 204, 384–397.

    Article  CAS  Google Scholar 

  19. Dellaporta, S. L., Wood, J., & Hicks, J. B. (1983). A plant DNA minipreparation: Version II. Plant Molecular Biology Reporter, 1, 19–21.

    Article  CAS  Google Scholar 

  20. Franklin, S., Ngo, B., Efuet, E., & Mayfield, S. P. (2002). Development of a GFP reporter gene for Chlamydomonas reinhardtii chloroplast. The Plant Journal, 30, 733–744.

    Article  CAS  Google Scholar 

  21. Rosales-Mendoza, S., Soria-Guerra, R. E., de Jesús Olivera-Flores, M. T., López-Revilla, R., Arguello-Astorga, G. R., Jiménez-Bremont, J. F., et al. (2007). Expression of Escherichia coli heat-labile enterotoxin b subunit (LTB) in carrot (Daucus carota L.). Plant Cell Reports, 26(7), 969–976.

    Article  CAS  Google Scholar 

  22. Gleba, Y., Marillonnet, S., & Klimyuk, V. (2014). Engineering viral expression vectors for plants: The ‘full virus’ and the ‘deconstructed virus’ strategies. Current Opinion in Plant Biology, 2, 182–188.

    Google Scholar 

  23. Rosales-Mendoza, S., Angulo, C., & Meza, B. (2016). Food-grade organisms as vaccine biofactories and oral delivery vehicles. Trends in Biotechnology, 34(2), 124–136.

    Article  CAS  Google Scholar 

  24. Spangler, B. D. (1992). Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microbiological Reviews, 56, 622–647.

    CAS  Google Scholar 

  25. Tochikubo, K., & Yasuda, Y. (2000). Principle of mucosal immunity and development of mucosal vaccines using cholera toxin B subunit and its related adjuvants. Recent Research Developments in Microbiology, 4, 387–405.

    Google Scholar 

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Acknowledgements

We acknowledge Elizabeth Monreal Escalante for providing anti-LTB serum and Sergio Zarazúa Guzman for providing anti-RAGE monoclonal antibody. Current investigations from the group are supported by CONACYT/México (Grant INFR-2016-271182 and CB-256063 to SRM) and PRODEP/UASLP México (Grant DSA/103.5/16/7283 to Benita Ortega Berlanga).

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Authors and Affiliations

  1. Laboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias Químicas, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, 78210, San Luis Potosí, SLP, Mexico

    Benita Ortega-Berlanga, Bernardo Bañuelos-Hernández & Sergio Rosales-Mendoza

  2. Sección de Biotecnología, Centro de Investigación en Ciencias de la Salud y Biomedicina, Universidad Autónoma de San Luis Potosí, Av. Dr. Manuel Nava 6, 78210, San Luis Potosí, SLP, Mexico

    Benita Ortega-Berlanga, Bernardo Bañuelos-Hernández & Sergio Rosales-Mendoza

Authors
  1. Benita Ortega-Berlanga
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  2. Bernardo Bañuelos-Hernández
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  3. Sergio Rosales-Mendoza
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Correspondence to Sergio Rosales-Mendoza.

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Ortega-Berlanga, B., Bañuelos-Hernández, B. & Rosales-Mendoza, S. Efficient Expression of an Alzheimer’s Disease Vaccine Candidate in the Microalga Schizochytrium sp. Using the Algevir System. Mol Biotechnol 60, 362–368 (2018). https://doi.org/10.1007/s12033-018-0077-4

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