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Volume 36 Issue 3
June 2021
    Citation: Ye Chen, Qibin Liao, Tianyue Chen, Yuchao Zhang, Weien Yuan, Jianqing Xu, Xiaoyan Zhang. Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities .VIROLOGICA SINICA, 2021, 36(3) : 365-372.  http://dx.doi.org/10.1007/s12250-020-00250-1
    shu

    Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities

    cstr: 32224.14.s12250-020-00250-1
    • 1.

      Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China

    • 2.

      Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200000, China

    • Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector vaccines such as adenovirus and poxvirus vaccines, dominate the vaccine market because their viral particles are able to replicate and proliferate in vivo and produce lasting immunity in a manner similar to natural infection. One challenge of human and livestock vaccination is vaccine stability related to the antigenicity and infectivity. Freeze-drying is the typical method to maintain virus vaccine stability, while cold chain transportation is required for temperatures about 2 ℃–8 ℃. The financial and technological resource requirements hinder vaccine distribution in underdeveloped areas. In this study, we developed a freeze-drying formula consisting of bovine serum albumin (BSA), L-glutamic acid (L-Glu), polyethylene glycol (PEG), and dextran (DEX) to improve the thermal stability and activity of viral vaccines, including vaccinia recombinant vaccine (rTTV-OVA) and adenovirus vaccine (Ad5-ENV). We compared a panel of five different formulations (PEG: DEX: BSA: L-GLU=50:9:0:0(#1), 50:5:4:0(#2), 50:10:9:0(#3), 50:0:0:9(#4), and 50:1:0:8(#5), respectively) and optimized the freeze-drying formula for rTTV-OVA and Ad5-ENV. We found that the freeze-drying formulations #2 and #3 could maintain rTTV-OVA infectivity at temperatures of 4 ℃ and 25 ℃ and that rTTV-OVA immunogenicity was retained during lyophilization. However, formulations #4 and #5 maintained Ad5-ENV infectivity under the same conditions, and Ad5-ENV immunogenicity had maximum retention with freeze-drying formulation #4. In summary, we developed new freeze-drying formulations that increased virus vaccine storage times and retained immunogenicity at an ambient temperature.

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      1. Abdul-Fattah AM, Truong-Le V, Yee L, Pan E, Ao Y, Kalonia DS, Pikal MJ (2007) Drying-induced variations in physico-chemical properties of amorphous pharmaceuticals and their impact on Stability Ⅱ: stability of a vaccine. Pharm Res 24:715–727
          doi: 10.1007/s11095-006-9191-2

      2. Babu GN, Bawari M (1997) Single microinjection of L-glutamate induces oxidative stress in discrete regions of rat brain. Biochem Mol Biol Int 43:1207–1217

      3. Baron MD, Iqbal M, Nair V (2018) Recent advances in viral vectors in veterinary vaccinology. Curr Opin Virol 29:1–7
          doi: 10.1016/j.coviro.2018.02.002

      4. Basu A, Domb AJ (2018) Recent advances in polyanhydride based biomaterials. Adv Mater 30:e1706815
          doi: 10.1002/adma.201706815

      5. Borde A, Larsson A, Holmgren J, Nygren E (2011) Preparation and evaluation of a freeze-dried oral killed cholera vaccine formulation. Eur J Pharm Biopharm 79:508–518
          doi: 10.1016/j.ejpb.2011.06.009

      6. Briggs H, Ilett S (1993) Weak link in vaccine cold chain. BMJ 306:557–558
          doi: 10.1136/bmj.306.6877.557

      7. Chen C, Han D, Cai C, Tang X (2010) An overview of liposome lyophilization and its future potential. J Control Release 142:299–311
          doi: 10.1016/j.jconrel.2009.10.024

      8. Chen S et al (2012) Investigation on formulation and preparation of adenovirus encoding human endostatin lyophilized powders. Int J Pharm 427:145–152
          doi: 10.1016/j.ijpharm.2011.12.056

      9. Hansen LJJ, Daoussi R, Vervaet C, Remon JP, De Beer TRM (2015) Freeze-drying of live virus vaccines: a review. Vaccine 33:5507–5519
          doi: 10.1016/j.vaccine.2015.08.085

      10. Jang YH, Seong BL (2013) Cross-protective immune responses elicited by live attenuated influenza vaccines. Yonsei Med J 54:271–282
          doi: 10.3349/ymj.2013.54.2.271

      11. Kasper JC, Friess W (2011) The freezing step in lyophilization: physico-chemical fundamentals, freezing methods and consequences on process performance and quality attributes of biopharmaceuticals. Eur J Pharm Biopharm 78:248–263
          doi: 10.1016/j.ejpb.2011.03.010

      12. Kraan H, van Herpen P, Kersten G, Amorij JP (2014) Development of thermostable lyophilized inactivated polio vaccine. Pharm Res 31:2618–2629
          doi: 10.1007/s11095-014-1359-6

      13. Lapuente D, Ruzsics Z, Thirion C, Tenbusch M (2018) Evaluation of adenovirus 19a as a novel vector for mucosal vaccination against influenza A viruses. Vaccine 36:2712–2720
          doi: 10.1016/j.vaccine.2018.02.075

      14. Madan M, Sikriwal D, Sharma G, Shukla N, Mandyal AK, Kale S, Gill D (2018) Rational design of heat stable lyophilized rotavirus vaccine formulations. Hum Vaccin Immunother 14:2132–2141
          doi: 10.1080/21645515.2018.1487499

      15. Melief CJ, van Hall T, Arens R, Ossendorp F, van der Burg SH (2015) Therapeutic cancer vaccines. J Clin Investig 125:3401–3412
          doi: 10.1172/JCI80009

      16. Meri S, Jordens M, Jarva H (2008) Microbial complement inhibitors as vaccines. Vaccine 26(Suppl 8):I113–I117

      17. Mody KT, Mahony D, Cavallaro AS, Stahr F, Qiao SZ, Mahony TJ, Mitter N (2014) Freeze-drying of ovalbumin loaded mesoporous silica nanoparticle vaccine formulation increases antigen stability under ambient conditions. Int J Pharm 465:325–332
          doi: 10.1016/j.ijpharm.2014.01.037

      18. Ohtake S, Martin RA, Saxena A, Lechuga Ballesteros D, Santiago AE, Barry EM, Le Truong V (2011) Formulation and stabilization of francisella tularensis live vaccine strain. J Pharm Sci-US 100:3076–3087
          doi: 10.1002/jps.22563

      19. Orr MT et al (2014) Elimination of the cold-chain dependence of a nanoemulsion adjuvanted vaccine against tuberculosis by lyophilization. J Control Release 177:20–26
          doi: 10.1016/j.jconrel.2013.12.025

      20. Peetermans J (1996) Factors affecting the stability of viral vaccines. Dev Biol Stand 87:97–101

      21. Prabhu M, Bhanuprakash V, Venkatesan G, Yogisharadhya R, Bora DP, Balamurugan V (2014) Evaluation of stability of live attenuated camelpox vaccine stabilized with different stabilizers and reconstituted with various diluents. Biologicals 42:169–175
          doi: 10.1016/j.biologicals.2014.02.001

      22. Qiu S et al (2014) Fusion-expressed CTB improves both systemic and mucosal T-cell responses elicited by an intranasal DNA priming/intramuscular recombinant vaccinia boosting regimen J. Immunol Res 2014: 308732

      23. Reid MC et al (2019) Models to predict the public health impact of vaccine resistance: a systematic review. Vaccine 37:4886–4895
          doi: 10.1016/j.vaccine.2019.07.013

      24. Shin WJ, Hara D, Gbormittah F, Chang H, Chang BS, Jung JU (2018) Development of thermostable lyophilized sabin inactivated poliovirus vaccine. Mbio 9: e02287-18

      25. Shokri S, Shahkarami MK, Shafyi A, Mohammadi A, Esna-Ashari F, Hamta A (2019) Evaluation of the thermal stability of live-attenuated Rubella vaccine (Takahashi strain) formulated and lyophilized in different stabilizers. J Virol Methods 264:18–22
          doi: 10.1016/j.jviromet.2018.08.013

      26. Siow CR, Wan SHP, Chan LW (2016) Application of freeze-drying in the development of oral drug delivery systems. Expert Opin Drug Deliv 13:1595–1608
          doi: 10.1080/17425247.2016.1198767

      27. Stewart M, Ward SJ, Drew J (2014) Use of adenovirus as a model system to illustrate a simple method using standard equipment and inexpensive excipients to remove live virus dependence on the cold-chain. Vaccine 32:2931–2938
          doi: 10.1016/j.vaccine.2014.02.033

      28. Walters RH, Bhatnagar B, Tchessalov S, Izutsu KI, Tsumoto K, Ohtake S (2014) Next generation drying technologies for pharmaceutical applications. J Pharm Sci 103:2673–2695
          doi: 10.1002/jps.23998

      29. Yusuf H, Nugraheni RW, Setyawan D (2019) Effect of cellulose derivative matrix and oligosaccharide on the solid state and physical characteristics of dimethyldioctadecylammoniumliposomes for vaccine. Res Pharm Sci 14:1–11
          doi: 10.4103/1735-5362.251847

      30. Zheng Y, Lee PW, Wang C, Thomas LD, Stewart PL, Steinmetz NF, Pokorski JK (2019) Freeze-drying to produce efficacious CPMV virus-like particles. Nano Lett 19: 2099–2105

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      Freeze-Drying Formulations Increased the Adenovirus and Poxvirus Vaccine Storage Times and Antigen Stabilities

        Corresponding author: Weien Yuan, yuanweien@126.com
        Corresponding author: Jianqing Xu, xujianqing@shphc.org.cn
        Corresponding author: Xiaoyan Zhang, zhangxiaoyan@shphc.org.cn
      • 1. Shanghai Public Health Clinical Center and Institutes of Biomedical Sciences, Fudan University, Shanghai 201508, China
      • 2. Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200000, China
      • Received Date: 19 April 2020
      • Published Date: 21 July 2020

      Abstract: 

      Successful vaccines induce specific immune responses and protect against various viral and bacterial infections. Noninactivated vaccines, especially viral vector vaccines such as adenovirus and poxvirus vaccines, dominate the vaccine market because their viral particles are able to replicate and proliferate in vivo and produce lasting immunity in a manner similar to natural infection. One challenge of human and livestock vaccination is vaccine stability related to the antigenicity and infectivity. Freeze-drying is the typical method to maintain virus vaccine stability, while cold chain transportation is required for temperatures about 2 ℃–8 ℃. The financial and technological resource requirements hinder vaccine distribution in underdeveloped areas. In this study, we developed a freeze-drying formula consisting of bovine serum albumin (BSA), L-glutamic acid (L-Glu), polyethylene glycol (PEG), and dextran (DEX) to improve the thermal stability and activity of viral vaccines, including vaccinia recombinant vaccine (rTTV-OVA) and adenovirus vaccine (Ad5-ENV). We compared a panel of five different formulations (PEG: DEX: BSA: L-GLU=50:9:0:0(#1), 50:5:4:0(#2), 50:10:9:0(#3), 50:0:0:9(#4), and 50:1:0:8(#5), respectively) and optimized the freeze-drying formula for rTTV-OVA and Ad5-ENV. We found that the freeze-drying formulations #2 and #3 could maintain rTTV-OVA infectivity at temperatures of 4 ℃ and 25 ℃ and that rTTV-OVA immunogenicity was retained during lyophilization. However, formulations #4 and #5 maintained Ad5-ENV infectivity under the same conditions, and Ad5-ENV immunogenicity had maximum retention with freeze-drying formulation #4. In summary, we developed new freeze-drying formulations that increased virus vaccine storage times and retained immunogenicity at an ambient temperature.

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