Comparative evaluation of production platforms for chicken egg-based vaccines and mulberry silkworm biotechnology

   Vaccines are well-known and the most cost-effective strategy for preventing and suppressing global infections. New manufacturing platforms are being developed for safe, rapid and large-scale production, the implementation of which can eliminate the inherent drawbacks of traditional production. Furthermore, new vaccine stabilization and delivery systems are being developed to overcome dependence on the "cold chain".

   The objective of this review is to compare the traditional and most widely used egg-based platform with a potential biotechnological platform based on silkworm (Bombyx mori) as an alternative platform.

   From a public health perspective, influenza remains the only human disease that requires annual vaccination. For this reason, the presented review largely reflects the peculiarities of this direction. A comprehensive comparative assessment of key manufacturing indicators at the stages of USP and DSP, reflecting their effectiveness, showed a significant advantage of mulberry silkworm-based biotechnological solutions over egg-based platform. The possibility of effectively using the obtained raw materials, both primary (cocoon shell from which biomaterials are obtained for stabilization and vaccine delivery after processing), and secondary, mulberry silkworm pupa which serves as a bioreactor for the production of the target protein (hemagglutinin, HA) shows the advantages of the mulberry silkworm-based platform and in terms of raw material versatility compared to the chicken egg-based platform, and relative to another alternative production platform developed based on cabbage looper (Trichoplusia ni) biotechnology.

1. Chen J., Liu Y., Tseng Y., Ma C. Better Influenza Vaccines: An Industry Perspective. Journal of biomedical science, 2020, vol. 27, no. 1, p. 33. DOI: 10.1186/s12929-020-0626-6.

2. Nuwarda R., Alharbi A., Kayser V. An Overview of Influenza Viruses and Vaccines. Vaccines, 2021, vol. 9, no. 9, p. 1032. DOI: 10.3390/vaccines9091032.

3. Sparrow E., Wood J., Chadwick C., Newall A., Torvaldsen S., Moen A., Torelli G. Global Production Capacity of Seasonal and Pandemic Influenza Vaccines in 2019. Vaccine, 2021, vol. 39, no. 3, pp. 512–520. DOI: 10.1016/j.vaccine.2020.12.018.

4. Cid R., Bolívar J. Platforms for Production of Protein-Based Vaccines: From Classical to Next-Generation Strategies. Biomolecules, 2021, vol. 11, no. 8, p. 1072. DOI: 10.3390/biom11081072.

5. Akbarian M., Chen S. Instability Challenges and Stabilization Strategies of Pharmaceutical Proteins. Pharmaceutics, 2022, vol. 14, no. 11, p. 2533. DOI: 10.3390/pharmaceutics14112533.

6. Bajrovic I., Schafer S., Romanovicz D., Croyle M. Novel Technology for Storage and Distribution of Live Vaccines and Other Biological Medicines at Ambient Temperature. Science advances, 2020, vol. 6, no. 10, p. 4819. DOI: 10.1126/sciadv.aau4819.

7. Bajrovic I., Croyle M. Challenges in Vaccine Transport: Can We Deliver Without the Cold Chain. Expert review of vaccines, 2023, vol. 22, no. 1, pp. 933–936. DOI: 10.1080/14760584.2023.2273901.

8. McNulty M., Gleba Y., Tusé D., Hahn Löbmann S., Giritch A., Nandi S., McDonald K. Techno-Economic Analysis of a Plant-Based Platform for Manufacturing Antimicrobial Proteins for Food Safety. Biotechnology progress, 2020, vol. 36, no. 1, p. 2896. DOI: 10.1002/btpr.2896.

9. Maegawa K., Sugita S., Arasaki Y., Nerome R., Nerome K. Interleukin 12-Containing Influenza Virus-Like-Particle Vaccine Elevate Its Protective Activity Against Heterotypic Influenza Virus Infection. Heliyon, 2020, vol. 6, no. 8. P. 04543. DOI: 10.1016/j.heliyon.2020.

10. Nerome K., Imagawa T., Sugita S., Arasaki Y., Maegawa K., Kawasaki K., Kajiura Z. The Potential of a Universal Influenza Virus-Like Particle Vaccine Expressing a Chimeric Cytokine. Life science alliance, 2023, vol. 6, no. 1, p. 202201548. DOI: 10.26508/lsa.202201548.

11. Vandyshev P.Е. Determination of parameters of chick embryos used in the production of inactivated influenza vaccines. Agrarniy nauchniy zhurnal = Agrarian Scientific Journal, 2023, no. 5, pp. 67–71. (In Russian). DOI: 10.28983/asj.y2023i5pp67-71.

12. Lamberti C., Gai F., Cirrincione S., Giribaldi M., Purrotti M., Manfredi M., Cavallarin L. Investigation of the Protein Profile of Silkworm (Bombyx mori) Pupae Reared on a Well-Calibrated Artificial Diet Compared to Mulberry Leaf Diet. Peer J, 2019, vol. 7, p. 6723. DOI: 10.7717/peerj.6723.

13. Joubrane K., Mnayer D., Hamieh T., Barbour G., Talhouk R., Awad E. Evaluation of Quality Parameters of White and Brown Eggs in Lebanon. American Journal of Analytical Chemistry, 2019, vol. 10, no. 10, pp. 488–503. DOI: 10.4236/ajac.2019.1010035.

14. Yagi H., Yanaka S., Yogo R., Ikeda A., Onitsuka M., Yamazaki T., Kato K. Silkworm Pupae Function as Efficient Producers of Recombinant Glycoproteins with Stable-Isotope Labeling. Biomolecules, 2020, vol. 10, no. 11, p. 1482. DOI: 10.3390/biom10111482.

15. Xu P., Zhang M., Qian P., Li J., Wang X., Wu Y. ITRAQ-Based Quantitative Proteomic Analysis of Digestive Juice Across the First 48 Hours of the Fifth Instar in Silkworm Larvae. International journal of molecular sciences, 2019, vol. 20, no. 24, p. 6113. DOI: 10.3390/ijms20246113.

16. Holtof M., Lenaerts C., Cullen D., Vanden Broeck J. Extracellular Nutrient Digestion and Absorption in the Insect Gut. Cell and tissue research, 2019, vol. 377, no. 3, pp. 397–414. DOI: 10.1007/s00441-019-03031-9.

17. Stinson J., Palmer C., Miller D., Li A., Lightner K., Jost H., Kosuda K. Thin Silk Fibroin Films as a Dried Format for Temperature Stabilization of Inactivated Polio Vaccine. Vaccine, 2020, vol. 38, no. 7, pp. 1652–1666. DOI: 10.1016/j.vaccine.2019.12.062.

18. Stinson J., Boopathy A., Cieslewicz B., Zhang Y., Hartman N., Miller D., Kosuda K. Enhancing Influenza Vaccine Immunogenicity and Efficacy Through Infection Mimicry Using Silk Microneedles. Vaccine, 2021, vol. 39, no. 38, pp. 5410–5421. DOI: 10.1016/j.vaccine.2021.07.064.

19. Yumatov E.N., Evlagina E.G., Evlagin V.G., Leinweber E.F., Tovpeko D.V., Debenok S.S. Possibilities of Bombyx mori (B. mori) biotechnological platform for regenerative medicine. Regeneratsiya organov i tkaney = Tissue and organ regeneration, 2024, vol. 1, no. 2, pp. 33–54. (In Russian). DOI: 10.60043/2949-5938-2023-2-33-54.

20. Astrakhantsev A.А. The productive performance in indicators of hens kept in cages with different stocking parameters. Ptitsevodstvo = Poultry farming, 2021, vol. 1, pp. 34–37. (In Russian). DOI: 10.33845/0033-3239-2021-70-1-34-37.

21. Evlagin V.G., Evlagina E.G., Leinweber E.F., Yumatov E.N. Development Dynamics of Kavkaz-2 and Sovetskaya-14 NGL Silkworm Caterpillars on Artificial Nutrient Medium IPS 7.2-G. Amurskiy zoologicheskiy zhurnal = Amurian Zoological Journal, 2023, vol. 15, no. 4, pp. 870–880. (In Russian). DOI: 10.33910/2686-9519-2023-15-4-870-880.

22. Escribano J., Cid M., Reytor E., Alvarado C., Nuñez M., Martínez-Pulgarín S., Dalton R. Chrysalises as Natural Production Units for Recombinant Subunit Vaccines. Journal of biotechnology, 2020, vol. 324, p. 100019. DOI: 10.1016/j.btecx.2020.100019.

23. Falcón A., Martínez-Pulgarín S., López-Serrano S., Reytor E., Cid M., Nuñez M., Escribano J. Development of a Fully Protective Pandemic Avian Influenza Subunit Vaccine in Insect Pupae. Viruses, 2024, vol. 16, no. 6, p. 829. DOI: 10.3390/v16060829.