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Aşı Geliştirmede Güncellemeler: Hayvan Deneylerinin Azaltılmasında İn Vitro Modellerin Rolü ve Güncel Gelişmeler

Yıl 2025, Cilt: 14 Sayı: 2, 78 - 85, 25.12.2025
https://doi.org/10.53913/aduveterinary.1662593

Öz

Amaç: Aşı değerlendirme yöntemlerindeki son gelişmeleri, özellikle in vivo testlerden in vitro testlere geçişi, aşı araştırma ve kalite kontrolünde hayvan deneylerini en aza indirgemek için geliştirilen yeni teknikleri gözden geçirmek ve analiz etmektir.
Gereç ve Yöntemler: Bu çalışma, aşı değerlendirme tekniklerindeki son gelişmelerin kapsamlı bir literatür taramasını gerçekleştirmiştir. Bu tarama, Avrupa Farmakopesi'ndeki değişiklikleri, hücre bazlı testleri, Modüler Bağışıklık In vitro Yapı (MIMIC) sistemini ve organoid modellerini içermektedir. İnceleme, bu yöntemlerin etkinliğini, sınırlamalarını ve potansiyel uygulamalarını değerlendirmek için hakemli makaleler, düzenleyici kılavuzlar ve endüstri raporları incelemiştir.
Bulgular: Hayvan bazlı testlerin in vitro alternatiflerle değiştirilmesinde önemli ilerlemeler kaydedilmiştir. Avrupa Farmakopesi, Fare Histamin Duyarlılaştırma Testi'nin (HIST) Çin Hamsteri Yumutalığı (CHO) hücresi kümelenme testi ile ve Tavşan Pirojenite Testi'nin (RPT) Monosit Aktivasyon Testi (MAT) ile değiştirilmesi gibi değişiklikler uygulamıştır. Hücre bazlı testler, aşı geliştirmenin erken aşamalarında umut verici sonuçlar gösterirken, MIMIC sistemi insan bağışıklık tepkilerini replike etmede etkinlik göstermiştir. Organoid modeller, özellikle tonsil organoidleri, karmaşık bağışıklık etkileşimlerini simüle etmek için değerli araçlar olarak ortaya çıkmıştır.

Etik Beyan

Bu makalenin yalnızca Animal Health Production and Hygiene dergisine sunulduğunu, basında yayınlanmadığını veya başka bir yerde yayınlanmak üzere değerlendirmede olmadığını yazılı olarak temin ederim. Sunulan çalışma tamamen özgündür ve daha önce herhangi bir formatta yayınlanmamıştır

Destekleyen Kurum

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Teşekkür

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Kaynakça

  • Acosta, A., Norazmi, M.N., Hernandez-Pando, R., Alvarez, N., Borrero, R., Infante, J.F., & Sarmiento, M.E. (2011). The importance of animal models in tuberculosis vaccine development. The Malaysian Journal of Medical Sciences, 18(4), 5.
  • Byers, A.M., Tapia, T.M., Sassano, E.R., & Wittman, V. (2009). In vitro antibody response to tetanus in the MIMIC™ system is a representative measure of vaccine immunogenicity. Biologicals, 37(3), 148-151. https://doi.org/10.1016/j.biologicals.2009.02.018
  • Calle, M.G.T. (2019). Human cell-based in vitro systems for vaccine evaluation. [Doctoral Thesis, University of Groningen]. https://doi.org/10.33612/diss.100812074
  • Curlin, G., Landry, S., Bernstein, J., Gorman, R.L., Mulach, B., Hackett, C.J., & Strickler-Dinglasan, P. (2011). Integrating safety and efficacy evaluation troughout vaccine research and development. Pediatrics, 127(1), 9-15. https://doi.org/10.1542/peds.2010-1722C
  • Dauner, A., Agrawal, P., Salvatico, J., Tapia, T., Dhir, V., Shaik, S.F., & Byers, A.M. (2017). The in vitro MIMIC® platform reflects ageassociated changes in immunological responses after influenza vaccination. Vaccine, 35(41), 5487-5494. https://doi.org/10.1016/j.vaccine.2017.03.099
  • De Rosa, S.C., Cohen, K.W., Bonaparte, M., Fu, B., Garg, S., Gerard, C., & McElrath, M.J. (2022). Whole‐blood cytokine secretion assay as a high‐throughput alternative for assessing the cell‐mediated immunity profile after two doses of an adjuvanted SARS‐CoV‐2 recombinant protein vaccine candidate. Clinical & Translational Immunology, 11(1), e1360. https://doi.org/10.1002/cti2.1360
  • Doss-Gollin, S., Thomas, S., Brook, B., Abedi, K., Lebas, C., Auderset, F., . . . & Levy, O. (2023). Human in vitro modeling of adjuvant formulations demonstrates enhancement of immune responses to SARS-CoV-2 antigen. npj Vaccines, 8(1), 163. https://doi.org/10.1038/s41541-023-00759-y
  • EDQM (2024). Replacement, Reduction and Refinement of Animal Testing (3Rs): Latest Achievements. European Directorate for the Quality of Medicines & HealthCare. Retrieved from https://www.edqm.eu/en/replacement-reduction-and-refinement-of-animaltesting-3rs-latest-achievements (accessed 15 March 2025)
  • Gaines-Das, R., Ochiai, M., Douglas-Bardsley, A., Asokanathan, C., Horiuchi, Y., Rigsby, P., & Xing, D.K. (2009). Transferability of dermal temperature histamine sensitization test for estimation of pertussis toxin activity in vaccines. Human vaccines, 5(3), 166-171. https://doi.org/10.4172/2157-7560.1000355
  • Gerdts, V., Wilson, H.L., Meurens, F., van Drunen Littel-van den Hurk, S., Wilson, D., Walker, S., & Potter, A.A. (2015). Large animal models for vaccine development and testing. ILAR Journal, 56 (1), 53-62. https://doi.org/10.1093/ilar/ilv009
  • Gomez, S.R. (2007). Investigation of pertussis toxin A-and B-subunit activities in acellular vaccines by enzymatic and carbohydratebinding assays. [PhD Thesis, University of Glasgow]
  • Greig, A.J. (2018). A Cell-Based Assay for the Safety Testing of Pertussis-Containing Vaccines. [Doctoral Thesis, University College London]. https://discovery.ucl.ac.uk/id/eprint/10048192
  • Higbee, R.G., Byers, A.M., Dhir, V., Drake, D., Fahlenkamp, H.G., Gangur, J., & Ma, Y. (2009). An immunologic model for rapid vaccine assessment—a clinical trial in a test tube. Alternatives to Laboratory Animals, 37 (1), 19-27. https://doi.org/10.1177/026119290903701S05
  • Hong, K.J., & Seo, S.H. (2018). Organoid as a culture system for viral vaccine strains. Clinical and Experimental Vaccine Research, 7(2), 145-148. https://doi.org/10.7774/cevr.2018.7.2.145
  • Hoonakker, M.E. (2021). In vivo models and in vitro assays for the assessment of pertussis toxin activity. Toxins, 13 (8), 565. https://doi.org/10.3390/toxins13080565
  • Isbrucker, R., Daas, A., Wagner, L., & Costanzo, A. (2016). Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines. Pharmeuropa Bio & Scientific Notes , 2015, 97-114. PMID: 27506252
  • Kastenschmidt, J.M., Sureshchandra, S., Jain, A., Hernandez-Davies, J.E., de Assis, R., Wagoner, Z.W., & Levendosky, E. (2023a). Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids. Immunity, 56 (8), 1910-1926. https://doi.org/10.1016/j.immuni.2023.06.019
  • Kastenschmidt, J.M., Sureshchandra, S., & Wagar, L.E. (2023b). Leveraging human immune organoids for rational vaccine design. Trends in Immunology. 44(12), 938-944. https://doi.org/10.1016/j.it.2023.10.008
  • Kiani, A.K., Pheby, D., Henehan, G., Brown, R., Sieving, P., Sykora, P., & Miertus, S. (2022). Ethical considerations regarding animal experimentation. Journal of Preventive Medicine and Hygiene, 63(2), E255. https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2768
  • Kiros, T.G., Levast, B., Auray, G., Strom, S., Van Kessel, J., & Gerdts, V. (2012). The importance of animal models in the development of vaccines. Innovation in Vaccinology: from design, through to delivery and testing. Springer, Dordrecht, 251-264. https://doi.org/10.1007/978-94-007-4543-8_11
  • Lu, L., Kong, W.Y., Zhang, J., Firdaus, F., Wells, J.W., Stephenson, R.J., & Cruz, J.L.G. (2024). Utilizing murine dendritic cell line DC2. 4 to evaluate the immunogenicity of subunit vaccines in vitro. Frontiers in Immunology, 15, 1298721. https://doi.org/10.3389/fimmu.2024.1298721
  • Ma, Y., Poisson, L., Sanchez‐Schmitz, G., Pawar, S., Qu, C., Randolph, G.J., & Higbee, R.G. (2010). Assessing the immunopotency of Tolllike receptor agonists in an in vitro tissue‐engineered immunological model. Immunology, 130(3), 374-387. https://doi.org/10.1111/j.1365-2567.2009.03237.x
  • Markey, K., Asokanathan, C., & Feavers, I. (2019). Assays for determining pertussis toxin activity in acellular pertussis vaccines. Toxins, 11(7), 417. https://doi.org/10.3390/toxins11070417
  • Metz, B., Van Den Dobbelsteen, G., Van Els, C., Van Der Gun, J., Levels, L., van Der Pol, L., & Kersten, G. (2009). Quality-control issues and approaches in vaccine development. Expert Review of Vaccines, 8(2), 227-238. https://doi.org/10.1586/14760584.8.2.227
  • Mirhassani, R., Seyedjafari, E., & Vaziri, B. (2024). A validated polyclonal antiserum-based immunoassay for assessment of HPV 16 L1 relative potency. Biologicals, 85, 101742. https://doi.org/10.1016/j.biologicals.2023.101742
  • Moeller, T.D., Shah, S.B., Lai, K., Lopez-Barbosa, N., Desai, P., Wang, W., & DeLisa, M.P. (2023). Profiling germinal center-like B cell responses to conjugate vaccines using synthetic immune organoids. ACS Central Science, 9(4), 787-804. https://doi.org/10.1021/acscentsci.2c01473
  • Morgeaux, S., Variot, P., Daas, A., & Costanzo, A. (2013). Validation of a new ELISA method for in vitro potency testing of hepatitis A vaccines. Pharmeuropa Bio & Scientific Notes, 64-92. PMID:24447723
  • Patel, N., Davis, Z., Hofmann, C., Vlasak, J., Loughney, J.W., DePhillips, P., & Mukherjee, M. (2023). Development and Characterization of an In Vitro Cell-Based Assay to Predict Potency of mRNA–LNPBased Vaccines. Vaccines, 11(7), 1224. https://doi.org/10.3390/vaccines11071224
  • Pullen, R.H., Sassano, E., Agrawal, P., Escobar, J., Chehtane, M., Schanen, B., & Brennan, R.J. (2024). A Predictive Model of Vaccine Reactogenicity Using Data from an In Vitro Human Innate Immunity Assay System. The Journal of Immunology, 212(5), 904-916. https://doi.org/10.4049/jimmunol.2300185
  • Sanyal, G. (2022). Development of functionally relevant potency assays for monovalent and multivalent vaccines delivered by evolving technologies. npj Vaccines, 7 (1), 50. https://doi.org/10.1038/s41541-022-00470-4
  • Sholukh, A.M., Fiore-Gartland, A., Ford, E.S., Miner, M.D., Hou, Y.J., Tse, L.V., & Madarampalli, B. (2021). Evaluation of cell-based and surrogate SARS-CoV-2 neutralization assays. Journal of Clinical Microbiology, 59 (10), e0052721. https://doi.org/10.1128/JCM.00527-21
  • Stephens, M., Alvino, G., & Branson, J. (2002). Animal pain and distress in vaccine testing in the United States. Developments in Biologicals, 111, 213-216. PMID: 12678244
  • Struck, M.M. (1996). Vaccine R&D success rates and development times. Nature Biotechnology, 14(5), 591-593. https://doi.org/10.1038/nbt0596-591
  • Tapia-Calle, G., Born, P.A., Koutsoumpli, G., Gonzalez-Rodriguez, M.I., Hinrichs, W.L., & Huckriede, A.L. (2019). A PBMC-based system to assess human T cell responses to influenza vaccine candidates in vitro. Vaccines, 7(4), 181. https://doi.org/10.3390/vaccines7040181
  • Tew, J.G., El Shikh, M.E.M., Singh, I., Mishkin, E., Drake III, D., Song, H., & Warren, W.L. (2010). Models for vaccine assessment. (U.S. Patent No: US20100287630A1). U.S. Patent and Trademark Office.
  • Ticha, O., Klemm, D., Moos, L., & Bekeredjian-Ding, I. (2021). A cellbased in vitro assay for testing of immunological integrity of Tetanus toxoid vaccine antigen. npj Vaccines, 6(1), 88. https://doi.org/10.1038/s41541-021-00344-1
  • Van den Biggelaar, R.H., Hoefnagel, M.H., Vandebriel, R.J., Sloots, A., Hendriksen, C.F., Van Eden, W.,& Jansen, C.A (2021). Overcoming scientific barriers in the transition from in vivo to non-animal batch testing of human and veterinary vaccines. Expert Review of Vaccines, 20 (10), 1221-1233. https://doi.org/10.1080/14760584.2021.1977628
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  • Xing, D., Maes, A., Behr-Gross, M., Costanzo, A., Daas, A., & Buchheit, K. (2010). Collaborative study for the standardisation of the histamine sensitizing test in mice and the CHO cell-based assay for the residual toxicity testing of acellular pertussis vaccines. Pharmeuropa Bio & Scientific Notes, 1, 51-63. PMID: 20223190
  • Zhang, X., Wu, X., He, Q., Wang, J., Mao, Q., Liang, Z., & Xu, M. (2023). Research progress on substitution of in vivo method (s) by in vitro method (s) for human vaccine potency assays. Expert Review of Vaccines, 22(1), 270-277. https://doi.org/10.1080/14760584.2023.2178421

Advancing Vaccine Development: The Role of In Vitro Models and Progress in Reducing Animal Testing

Yıl 2025, Cilt: 14 Sayı: 2, 78 - 85, 25.12.2025
https://doi.org/10.53913/aduveterinary.1662593

Öz

Aim: To review and analyse recent advancements in vaccine evaluation methods, focusing on the transition from in vivo to in vitro assays and the development of novel techniques to minimize animal testing in vaccine research and quality control.
Materials and Methods: This study conducted a comprehensive literature review of recent developments in vaccine evaluation techniques, including modifications to the European Pharmacopoeia, cell-based assays, the Modular Immune In vitro Construct (MIMIC) system, and organoid models. The review examined articles, regulatory guidelines, and industry reports to assess the efficacy, limitations, and potential applications of these methods.
Results: Significant progress has been made in replacing animal-based tests with in vitro alternatives. The European Pharmacopoeia has implemented changes such as replacing the Mouse Histamine Sensitization Test (HIST) with the Chinese Hamster Ovary (CHO) cell clustering test and the Rabbit Pyrogenicity Test (RPT) with the Monocyte Activation Test (MAT). Cell-based assays have shown promise in early vaccine development stages, while the MIMIC system has demonstrated effectiveness in replicating human immune responses. Organoid models, particularly tonsil organoids, have emerged as valuable tools for simulating complex immune interactions.

Etik Beyan

I hereby provide written assurance that this manuscript has been submitted solely to Animal Health Production and Hygiene and is not published in the press or under consideration for publication elsewhere. The work presented is entirely original and has not been published previously in any format.

Destekleyen Kurum

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Teşekkür

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Kaynakça

  • Acosta, A., Norazmi, M.N., Hernandez-Pando, R., Alvarez, N., Borrero, R., Infante, J.F., & Sarmiento, M.E. (2011). The importance of animal models in tuberculosis vaccine development. The Malaysian Journal of Medical Sciences, 18(4), 5.
  • Byers, A.M., Tapia, T.M., Sassano, E.R., & Wittman, V. (2009). In vitro antibody response to tetanus in the MIMIC™ system is a representative measure of vaccine immunogenicity. Biologicals, 37(3), 148-151. https://doi.org/10.1016/j.biologicals.2009.02.018
  • Calle, M.G.T. (2019). Human cell-based in vitro systems for vaccine evaluation. [Doctoral Thesis, University of Groningen]. https://doi.org/10.33612/diss.100812074
  • Curlin, G., Landry, S., Bernstein, J., Gorman, R.L., Mulach, B., Hackett, C.J., & Strickler-Dinglasan, P. (2011). Integrating safety and efficacy evaluation troughout vaccine research and development. Pediatrics, 127(1), 9-15. https://doi.org/10.1542/peds.2010-1722C
  • Dauner, A., Agrawal, P., Salvatico, J., Tapia, T., Dhir, V., Shaik, S.F., & Byers, A.M. (2017). The in vitro MIMIC® platform reflects ageassociated changes in immunological responses after influenza vaccination. Vaccine, 35(41), 5487-5494. https://doi.org/10.1016/j.vaccine.2017.03.099
  • De Rosa, S.C., Cohen, K.W., Bonaparte, M., Fu, B., Garg, S., Gerard, C., & McElrath, M.J. (2022). Whole‐blood cytokine secretion assay as a high‐throughput alternative for assessing the cell‐mediated immunity profile after two doses of an adjuvanted SARS‐CoV‐2 recombinant protein vaccine candidate. Clinical & Translational Immunology, 11(1), e1360. https://doi.org/10.1002/cti2.1360
  • Doss-Gollin, S., Thomas, S., Brook, B., Abedi, K., Lebas, C., Auderset, F., . . . & Levy, O. (2023). Human in vitro modeling of adjuvant formulations demonstrates enhancement of immune responses to SARS-CoV-2 antigen. npj Vaccines, 8(1), 163. https://doi.org/10.1038/s41541-023-00759-y
  • EDQM (2024). Replacement, Reduction and Refinement of Animal Testing (3Rs): Latest Achievements. European Directorate for the Quality of Medicines & HealthCare. Retrieved from https://www.edqm.eu/en/replacement-reduction-and-refinement-of-animaltesting-3rs-latest-achievements (accessed 15 March 2025)
  • Gaines-Das, R., Ochiai, M., Douglas-Bardsley, A., Asokanathan, C., Horiuchi, Y., Rigsby, P., & Xing, D.K. (2009). Transferability of dermal temperature histamine sensitization test for estimation of pertussis toxin activity in vaccines. Human vaccines, 5(3), 166-171. https://doi.org/10.4172/2157-7560.1000355
  • Gerdts, V., Wilson, H.L., Meurens, F., van Drunen Littel-van den Hurk, S., Wilson, D., Walker, S., & Potter, A.A. (2015). Large animal models for vaccine development and testing. ILAR Journal, 56 (1), 53-62. https://doi.org/10.1093/ilar/ilv009
  • Gomez, S.R. (2007). Investigation of pertussis toxin A-and B-subunit activities in acellular vaccines by enzymatic and carbohydratebinding assays. [PhD Thesis, University of Glasgow]
  • Greig, A.J. (2018). A Cell-Based Assay for the Safety Testing of Pertussis-Containing Vaccines. [Doctoral Thesis, University College London]. https://discovery.ucl.ac.uk/id/eprint/10048192
  • Higbee, R.G., Byers, A.M., Dhir, V., Drake, D., Fahlenkamp, H.G., Gangur, J., & Ma, Y. (2009). An immunologic model for rapid vaccine assessment—a clinical trial in a test tube. Alternatives to Laboratory Animals, 37 (1), 19-27. https://doi.org/10.1177/026119290903701S05
  • Hong, K.J., & Seo, S.H. (2018). Organoid as a culture system for viral vaccine strains. Clinical and Experimental Vaccine Research, 7(2), 145-148. https://doi.org/10.7774/cevr.2018.7.2.145
  • Hoonakker, M.E. (2021). In vivo models and in vitro assays for the assessment of pertussis toxin activity. Toxins, 13 (8), 565. https://doi.org/10.3390/toxins13080565
  • Isbrucker, R., Daas, A., Wagner, L., & Costanzo, A. (2016). Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines. Pharmeuropa Bio & Scientific Notes , 2015, 97-114. PMID: 27506252
  • Kastenschmidt, J.M., Sureshchandra, S., Jain, A., Hernandez-Davies, J.E., de Assis, R., Wagoner, Z.W., & Levendosky, E. (2023a). Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids. Immunity, 56 (8), 1910-1926. https://doi.org/10.1016/j.immuni.2023.06.019
  • Kastenschmidt, J.M., Sureshchandra, S., & Wagar, L.E. (2023b). Leveraging human immune organoids for rational vaccine design. Trends in Immunology. 44(12), 938-944. https://doi.org/10.1016/j.it.2023.10.008
  • Kiani, A.K., Pheby, D., Henehan, G., Brown, R., Sieving, P., Sykora, P., & Miertus, S. (2022). Ethical considerations regarding animal experimentation. Journal of Preventive Medicine and Hygiene, 63(2), E255. https://doi.org/10.15167/2421-4248/jpmh2022.63.2S3.2768
  • Kiros, T.G., Levast, B., Auray, G., Strom, S., Van Kessel, J., & Gerdts, V. (2012). The importance of animal models in the development of vaccines. Innovation in Vaccinology: from design, through to delivery and testing. Springer, Dordrecht, 251-264. https://doi.org/10.1007/978-94-007-4543-8_11
  • Lu, L., Kong, W.Y., Zhang, J., Firdaus, F., Wells, J.W., Stephenson, R.J., & Cruz, J.L.G. (2024). Utilizing murine dendritic cell line DC2. 4 to evaluate the immunogenicity of subunit vaccines in vitro. Frontiers in Immunology, 15, 1298721. https://doi.org/10.3389/fimmu.2024.1298721
  • Ma, Y., Poisson, L., Sanchez‐Schmitz, G., Pawar, S., Qu, C., Randolph, G.J., & Higbee, R.G. (2010). Assessing the immunopotency of Tolllike receptor agonists in an in vitro tissue‐engineered immunological model. Immunology, 130(3), 374-387. https://doi.org/10.1111/j.1365-2567.2009.03237.x
  • Markey, K., Asokanathan, C., & Feavers, I. (2019). Assays for determining pertussis toxin activity in acellular pertussis vaccines. Toxins, 11(7), 417. https://doi.org/10.3390/toxins11070417
  • Metz, B., Van Den Dobbelsteen, G., Van Els, C., Van Der Gun, J., Levels, L., van Der Pol, L., & Kersten, G. (2009). Quality-control issues and approaches in vaccine development. Expert Review of Vaccines, 8(2), 227-238. https://doi.org/10.1586/14760584.8.2.227
  • Mirhassani, R., Seyedjafari, E., & Vaziri, B. (2024). A validated polyclonal antiserum-based immunoassay for assessment of HPV 16 L1 relative potency. Biologicals, 85, 101742. https://doi.org/10.1016/j.biologicals.2023.101742
  • Moeller, T.D., Shah, S.B., Lai, K., Lopez-Barbosa, N., Desai, P., Wang, W., & DeLisa, M.P. (2023). Profiling germinal center-like B cell responses to conjugate vaccines using synthetic immune organoids. ACS Central Science, 9(4), 787-804. https://doi.org/10.1021/acscentsci.2c01473
  • Morgeaux, S., Variot, P., Daas, A., & Costanzo, A. (2013). Validation of a new ELISA method for in vitro potency testing of hepatitis A vaccines. Pharmeuropa Bio & Scientific Notes, 64-92. PMID:24447723
  • Patel, N., Davis, Z., Hofmann, C., Vlasak, J., Loughney, J.W., DePhillips, P., & Mukherjee, M. (2023). Development and Characterization of an In Vitro Cell-Based Assay to Predict Potency of mRNA–LNPBased Vaccines. Vaccines, 11(7), 1224. https://doi.org/10.3390/vaccines11071224
  • Pullen, R.H., Sassano, E., Agrawal, P., Escobar, J., Chehtane, M., Schanen, B., & Brennan, R.J. (2024). A Predictive Model of Vaccine Reactogenicity Using Data from an In Vitro Human Innate Immunity Assay System. The Journal of Immunology, 212(5), 904-916. https://doi.org/10.4049/jimmunol.2300185
  • Sanyal, G. (2022). Development of functionally relevant potency assays for monovalent and multivalent vaccines delivered by evolving technologies. npj Vaccines, 7 (1), 50. https://doi.org/10.1038/s41541-022-00470-4
  • Sholukh, A.M., Fiore-Gartland, A., Ford, E.S., Miner, M.D., Hou, Y.J., Tse, L.V., & Madarampalli, B. (2021). Evaluation of cell-based and surrogate SARS-CoV-2 neutralization assays. Journal of Clinical Microbiology, 59 (10), e0052721. https://doi.org/10.1128/JCM.00527-21
  • Stephens, M., Alvino, G., & Branson, J. (2002). Animal pain and distress in vaccine testing in the United States. Developments in Biologicals, 111, 213-216. PMID: 12678244
  • Struck, M.M. (1996). Vaccine R&D success rates and development times. Nature Biotechnology, 14(5), 591-593. https://doi.org/10.1038/nbt0596-591
  • Tapia-Calle, G., Born, P.A., Koutsoumpli, G., Gonzalez-Rodriguez, M.I., Hinrichs, W.L., & Huckriede, A.L. (2019). A PBMC-based system to assess human T cell responses to influenza vaccine candidates in vitro. Vaccines, 7(4), 181. https://doi.org/10.3390/vaccines7040181
  • Tew, J.G., El Shikh, M.E.M., Singh, I., Mishkin, E., Drake III, D., Song, H., & Warren, W.L. (2010). Models for vaccine assessment. (U.S. Patent No: US20100287630A1). U.S. Patent and Trademark Office.
  • Ticha, O., Klemm, D., Moos, L., & Bekeredjian-Ding, I. (2021). A cellbased in vitro assay for testing of immunological integrity of Tetanus toxoid vaccine antigen. npj Vaccines, 6(1), 88. https://doi.org/10.1038/s41541-021-00344-1
  • Van den Biggelaar, R.H., Hoefnagel, M.H., Vandebriel, R.J., Sloots, A., Hendriksen, C.F., Van Eden, W.,& Jansen, C.A (2021). Overcoming scientific barriers in the transition from in vivo to non-animal batch testing of human and veterinary vaccines. Expert Review of Vaccines, 20 (10), 1221-1233. https://doi.org/10.1080/14760584.2021.1977628
  • Wagar, L.E., Salahudeen, A., Constantz, C.M., Wendel, B.S., Lyons, M.M., Mallajosyula, V., & Gupta, N. (2021). Modeling human adaptive immune responses with tonsil organoids. Nature Medicine, 27(1), 125-135. https://doi.org/10.1038/s41591-020-01145-0
  • WHO (2019). Global Market Study: Diphtheria and Tetanuscontaining Vaccines. World Health Organization. Retrieved from https://cdn.who.int/media/docs/default-source/immunization/mi4a/dt_market_study_public_summary may2019.pdf?sfvrsn=ddfb81b8_6&download=true (accessed 15 Feb 2025).
  • Wong, C.H., Siah, K.W., & Lo, A.W. (2019). Estimation of clinical trial success rates and related parameters. Biostatistics, 20(2), 273-286. https://doi.org/10.1093/biostatistics/kxx069
  • Xing, D., Maes, A., Behr-Gross, M., Costanzo, A., Daas, A., & Buchheit, K. (2010). Collaborative study for the standardisation of the histamine sensitizing test in mice and the CHO cell-based assay for the residual toxicity testing of acellular pertussis vaccines. Pharmeuropa Bio & Scientific Notes, 1, 51-63. PMID: 20223190
  • Zhang, X., Wu, X., He, Q., Wang, J., Mao, Q., Liang, Z., & Xu, M. (2023). Research progress on substitution of in vivo method (s) by in vitro method (s) for human vaccine potency assays. Expert Review of Vaccines, 22(1), 270-277. https://doi.org/10.1080/14760584.2023.2178421
Toplam 42 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Veteriner Bilimleri (Diğer)
Bölüm Derleme
Yazarlar

Mehtap Tuğba Dokumacı 0000-0002-2310-326X

Semra Soydam 0009-0007-4394-7009

Gönderilme Tarihi 21 Mart 2025
Kabul Tarihi 5 Ağustos 2025
Yayımlanma Tarihi 25 Aralık 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 14 Sayı: 2

Kaynak Göster

APA Dokumacı, M. T., & Soydam, S. (2025). Advancing Vaccine Development: The Role of In Vitro Models and Progress in Reducing Animal Testing. Animal Health Production and Hygiene, 14(2), 78-85. https://doi.org/10.53913/aduveterinary.1662593