Journals / Kocatepe Tıp Dergisi / 2026 / Cilt: 27 Sayı: 4

ANTIGEN PRODUCTION IN THE VACCINE DEVELOPMENT PROCESS; METHODS AND INNOVATIVE APPROACHES

AŞI GELİŞTİRME SÜRECİNDE ANTİJEN ÜRETİMİ; YÖNTEMLER VE YENİLİKÇİ YAKLAŞIMLAR

Buse Türegün Atasoy(HACETTEPE ÜNİVERSİTESİ)0000-0002-8328-7291
Semra Soydam(HACETTEPE ÜNİVERSİTESİ)0009-0007-4394-7009
Pages
575–585
Publication Date
2026-10-12
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

In conclusion, the selection of an appropriate antigen and production platform, together with the optimization of production processes, is critical for the development of safe and effective vaccines.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Vaccination is one of the most effective and safe preventive health measures for public health.
📊
Key Findings & Data:Antigens, the main components of vaccines, may include proteins, carbohydrates, toxins, and nucleic acids and require different production methods depending on their characteristics.
💡
Conclusion & Impact:In conclusion, the selection of an appropriate antigen and production platform, together with the optimization of production processes, is critical for the development of safe and effective vaccines.
🔬Design:Review & Systematic Survey
📍Scope:Comprehensive Sample
⚙️Variables:Aşılar · Aşılama · Antijen

Abstract

Vaccination is one of the most effective and safe preventive health measures for public health. Since Edward Jenner developed the smallpox vaccine, vaccines have played an important role in the prevention and control of infectious diseases. Vaccine production is a multi-stage process involving the selection, design, production, and purification of antigens capable of effectively stimulating the immune system. Antigens, the main components of vaccines, may include proteins, carbohydrates, toxins, and nucleic acids and require different production methods depending on their characteristics. This review discusses antigen production approaches for live attenuated, inactivated, toxoid, recombinant protein, nucleic acid, conjugate polysaccharide, virus-like particle (VLP), outer membrane vesicle (OMV), and viral vector-based vaccines. Fundamental production steps, including antigen design, cultivation and expression systems, inactivation, isolation, purification, and formulation, are evaluated, and the advantages, limitations, and effects of different approaches on immunogenicity are compared. In addition to conventional methods, advances in recombinant DNA technologies, nucleic acid-based platforms, and next-generation antigen delivery systems have contributed to faster and more flexible vaccine development processes. In conclusion, the selection of an appropriate antigen and production platform, together with the optimization of production processes, is critical for the development of safe and effective vaccines.

Özet

Aşılama, toplum sağlığı açısından en etkili ve güvenli koruyucu sağlık hizmetlerinden biridir. Edward Jenner’ın çiçek aşısını geliştirmesinden bu yana aşılar, bulaşıcı hastalıkların önlenmesi ve kontrolünde önemli başarılar sağlamıştır. Aşı üretimi, bağışıklık sistemini etkin şekilde uyarabilen antijenlerin seçimi, tasarımı, üretimi ve saflaştırılmasını içeren çok aşamalı bir süreçtir. Aşıların temel bileşeni olan antijenler; proteinler, karbonhidratlar, toksinler ve nükleik asitler gibi farklı yapılarda olabilir ve özelliklerine göre farklı üretim yöntemleri gerektirir. Bu derlemede; canlı atenüe, inaktif, toksoid, rekombinant protein, nükleik asit, konjuge polisakkarit, virüs benzeri partikül (VLP), dış membran vezikülü (OMV) ve viral vektör tabanlı aşıların antijen üretim yaklaşımları ele alınmıştır. Bu platformlarda kullanılan antijen tasarımı, kültivasyon ve ekspresyon sistemleri, inaktivasyon, izolasyon, saflaştırma ve formülasyona yönelik temel üretim basamakları değerlendirilmiş; farklı yaklaşımların avantajları, sınırlılıkları ve immünojenite üzerindeki etkileri karşılaştırılmıştır. Geleneksel yöntemlerin yanı sıra rekombinant DNA teknolojileri, nükleik asit temelli platformlar ve yeni nesil antijen sunum sistemlerindeki gelişmeler, aşı geliştirme süreçlerinin daha hızlı ve esnek hâle gelmesine katkı sağlamaktadır. Sonuç olarak, uygun antijenin ve üretim platformunun seçimi ile üretim süreçlerinin optimizasyonu, güvenli ve etkili aşıların geliştirilmesinde kritik öneme sahiptir.

🔖

Cite This Article

Atasoy, B. T., Soydam, S. (2026). ANTIGEN PRODUCTION IN THE VACCINE DEVELOPMENT PROCESS; METHODS AND INNOVATIVE APPROACHES. Kocatepe Tıp Dergisi, Cilt: 27 Sayı: 4, 575–585. https://doi.org/10.18229/kocatepetip.1650432

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (53)

  1. Poria R, Kala D, Nagraik R, et al. Vaccine development: current trends and technologies. Life Sci. 2024;336:122331.
  2. Wilder-Smith A. Dengue vaccine development: challenges and prospects. Curr Opin Infect Dis. 2022;35(5):390-6.
  3. Abbas AK, Lichtman AH, Pillai S, Baker DL (Edited by). Cellular and molecular immunology. 10th Edition, Philadelphia: Elsevier. 2022:130-55.
  4. Delves PJ, Roitt IM (Edited by). Roitt's essential immunology. 12th Edition, Chichester: Wiley-Blackwell, 2011:40- 84.
  5. Roitt IM, Brostoff J, Male DK (Edited by). Immunology. 6th Edition, Edinburgh: Mosby. 2001:55-72.
  6. Plotkin S, Robinson JM, Cunningham G, et al. The complexity and cost of vaccine manufacturing – An overview. Vaccine. 2017;35(33):4064-71.
  7. Khudainazarova NS, Granovskiy DL, Kondakova OA, et al. Prokaryote- and eukaryote-based expression systems: advances in post-pandemic viral antigen production for vaccines. Int J Mol Sci. 2024;25(22):11979.
  8. Krämer A, Kretzschmar M, Krickeberg K (Edited by). Modern Infectious Disease Epidemiology. In: Pebody R, Kretzschmar M. Principles and practice of vaccinology. New York: Springer. 2010:235-48.
  9. Plotkin SA, Orenstein WA, Offit PA (Edited by). Plotkin's vaccines. 7th Edition, Philadelphia: Elsevier. 2018:67-81.
  10. Cunningham AL, Garçon N, Leo O, et al. Vaccine development: from concept to early clinical testing. Vaccine. 2016;34(52):6655-64.
  11. Minor PD. Live attenuated vaccines: historical successes and current challenges. Virology. 2015;479:379-92.
  12. Besnard L, Fabre V, Fettig M, et al. Clarification of vaccines: an overview of filter based technology trends and best practices. Biotechnol Adv. 2016;34(1):1-13.
  13. Goller CC, Seed PC. Coming of AGE: facile generation of attenuated vaccine strains through heterologous gene expression. Virulence. 2012;3(1):12-4.
  14. Hajra D, Datey A, Chakravortty D. Attenuation methods for live vaccines. Methods Mol Biol. 2021;2183:331-56.
  15. Kato A. [Effects of virus mutations caused by passages on vaccinal immunogenicity]. Nihon Rinsho. 2008;66(10):1908-14.
  16. Saleh A, Qamar S, Tekin A, et al. Vaccine development throughout history. Cureus. 2021;13(7):e16635.
  17. Lee S, Nguyen MT. Recent advances of vaccine adjuvants for infectious diseases. Immune Netw. 2015;15(2):51-7.
  18. Croda J, Ranzani OT. Booster doses for inactivated COVID-19 vaccines: if, when, and for whom. Lancet Infect Dis. 2022;22(4):430-2.
  19. Aubrit F, Perugi F, Léon A, et al. Cell substrates for the production of viral vaccines. Vaccine. 2015;33(44):5905- 12.
  20. Delrue I, Verzele D, Madder A, et al. Inactivated virus vaccines from chemistry to prophylaxis: merits, risks and challenges. Expert Rev Vaccines. 2012;11(6):695-719.
  21. Elveborg S, Monteil VM, Mirazimi A. Methods of inactivation of highly pathogenic viruses for molecular, serology or vaccine development purposes. Pathogens. 2022;11(2):271.
  22. Pollard AJ, Bijker EM. A guide to vaccinology: from basic principles to new developments. Nat Rev Immunol. 2021;21(2):83-100.
  23. Kovpak AA, Piniaeva AN, Gerasimov OA, et al. Methodology of purification of inactivated cell-culture-grown SARS-CoV-2 using size-exclusion chromatography. Vaccines (Basel). 2022;10(6):949.
  24. Pace JL, Rossi HA, Esposito VM, Frey SM, Tucker KD, Walker RI. Inactivated whole-cell bacterial vaccines: current status and novel strategies. Vaccine. 1998;16(16):1563-74.
  25. Prygiel M, Mosiej E, Gorska P, Zasada AA. Diphtheria-tetanus-pertussis vaccine: past, current & future. Future Microbiol. 2022;17:185-97.
  26. Metz B, Tilstra W, van der Put R, et al. Physicochemical and immunochemical assays for monitoring consistent production of tetanus toxoid. Biologicals. 2013;41(4):231-7.
  27. Hesari T, Tahoori F, Nazari A, et al. Investigation of the effect of PEG detoxification on diphtheria vaccine. Arch Razi Inst. 2022;77(2):739-45.
  28. Cid R, Bolivar J. Platforms for production of protein-based vaccines: from classical to next-generation strategies. Biomolecules. 2021;11(8):1072.
  29. Mikic A, Alomari A, Gowers DM. Classical recombinant DNA cloning. Methods Mol Biol. 2023;2633:1-24.
  30. Bill RM. Recombinant protein subunit vaccine synthesis in microbes: a role for yeast? J Pharm Pharmacol. 2015;67(3):319-28.
  31. Rancour DM, Backues SK, Bednarek SY. Protein antigen expression in Escherichia coli for antibody production. Methods Mol Biol. 2010;657:3-20.
  32. Structural Genomics Consortium, China Structural Genomics Consortium, Northeast Structural Genomics Consortium, et al. Protein production and purification. Nat Methods. 2008;5(2):135-46.
  33. Bello MB, Alsaadi A, Naeem A, et al. Development of nucleic acid-based vaccines against dengue and other mosquito-borne flaviviruses: the past, present, and future. Front Immunol. 2024;15:1475886.
  34. Kutzler MA, Weiner DB. DNA vaccines: ready for prime time? Nat Rev Genet. 2008;9(10):776-88.
  35. Fang E, Liu X, Li M, et al. Advances in COVID-19 mRNA vaccine development. Signal Transduct Target Ther. 2022;7(1):94.
  36. Pascolo S. Messenger RNA-based vaccines. Expert Opin Biol Ther. 2004;4(8):1285-94.
  37. Schlake T, Thess A, Fotin-Mleczek M, et al. Developing mRNA-vaccine technologies. RNA Biol. 2012;9(11):1319- 30.
  38. Carboni F, Adamo R. Structure-based glycoconjugate vaccine design: the example of Group B Streptococcus type III capsular polysaccharide. Drug Discov Today Technol. 2020;35-36:23-33.
  39. Huang Y, Chen H, Zhang K, et al. Extraction, purification, structural characterization, and gut microbiota relationship of polysaccharides: a review. Int J Biol Macromol. 2022;213:967-86.
  40. Qiu SM, Aweya JJ, Liu XJ, et al. Bioactive polysaccharides from red seaweed as potent food supplements: a systematic review of their extraction, purification, and biological activities. Carbohydr Polym. 2022;275:118696.
  41. Ji XL, Peng BX, Ding HH, et al. Purification, structure and biological activity of pumpkin polysaccharides: a review. Food Rev Int. 2023;39(1):307-19.
  42. Morais V, Suarez N. Conjugation mechanism for pneumococcal glycoconjugate vaccines: classic and emerging methods. Bioengineering (Basel). 2022;9(12):774.
  43. Chackerian B. Virus-like particles: flexible platforms for vaccine development. Expert Rev Vaccines. 2007;6(3):381-90.
  44. Kheirvari M, Liu H, Tumban E. Virus-like particle vaccines and platforms for vaccine development. Viruses. 2023;15(5):1109.
  45. Nooraei S, Bahrulolum H, Hoseini ZS, et al. Virus-like particles: preparation, immunogenicity and their roles as nanovaccines and drug nanocarriers. J Nanobiotechnology. 2021;19(1):59.
  46. Noad R, Roy P. Virus-like particles as immunogens. Trends Microbiol. 2003;11(9):438-44.
  47. Schwechheimer C, Kuehn MJ. Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol. 2015;13(10):605-19.
  48. Acevedo R, Fernández S, Zayas C, et al. Bacterial outer membrane vesicles and vaccine applications. Front Immunol. 2014;5:121.
  49. Ellis TN, Kuehn MJ. Virulence and immunomodulatory roles of bacterial outer membrane vesicles. Microbiol Mol Biol Rev. 2010;74(1):81-94.
  50. Deng S, Liang H, Chen P, et al. Viral vector vaccine development and application during the COVID-19 pandemic. Microorganisms. 2022;10(7):1450.
  51. Tang J, Amin MA, Campian JL. Past, present, and future of viral vector vaccine platforms: a comprehensive review. Vaccines (Basel). 2025;13(5):524.
  52. Travieso T, Li J, Mahesh S, et al. The use of viral vectors in vaccine development. NPJ Vaccines. 2022;7(1):75.
  53. Ünsal P, Özdemir S, Eroğlu Bayrak NH. Evaluation of adult patients' attitudes and behaviors about influenza, pneumococcal, herpes zoster and tetanus vaccines: a single-center survey study. Kocatepe Tıp Dergisi. 2023;24(3):314-21.