ALT ÜNİTE BAZLI AŞILARIN PULMONER UYGULAMASINA GENEL BAKIŞ

Yıl 2021, Cilt: 45 Sayı: 1, 109 - 130, 18.01.2021

Melike Ongun Başaran Mutlu-ağardan Fusun Acarturk

https://doi.org/10.33483/jfpau.800507

Öz

Amaç: Son yıllarda pulmoner bağışıklama parenteral aşılamaya ilişkin sorunları ortadan kaldırması, hem sistemik hem de mukozal bağışıklığı indüklemesi ile ilgi odağı olmuştur. Bu derlemede, inhale alt birim aşı çalışmaları ve gelişmeleri ele alınmıştır.

Sonuç ve Tartışma: Tüm patojen bazlı aşılara kıyasla daha güvenli olan alt birim aşılar, karmaşık yapılı patojenlerin neden olduğu hastalıklarda spesifik ve koruyucu bağışıklık yanıtı oluşturmaktadır. Bu aşıların, çeşitli taşıyıcı sistemler ve adjuvanlarla formüle edildiklerinde, solunum sisteminde hedeflenen bölgede spesifik immün yanıt oluşturduğu yapılan çalışmalarla gösterilmiştir. Son yıllarda konu ile ilgili yapılan araştırmalar stabil, invazif olmayan, soğuk zincir gerektirmeyen, kitlesel aşılamaya uygun kuru toz inhale aşıların formülasyonlarının geliştirilmesi ve bu aşılara uygun tek kullanımlık cihaz tasarımı üzerine odaklanmaktadır.

Anahtar Kelimeler

Alt birim aşı, inhale aşı, pulmoner bağışıklama

AN OVERVIEW OF SUBUNIT-BASED VACCINES FOR PULMONARY ADMINISTRATION

Öz

Objective: In recent years, pulmonary immunization has been the center of interest as it eliminates the problems related the parenteral vaccination and induces both systemic and mucosal immunity. In this review, the inhaled subunit vaccination studies and recent developments have been discussed.

Result and Discussion: Subunit vaccines, which are safer compared to whole pathogen-based vaccines, have provided a specific and protective immune response in diseases caused by complex pathogens. It has been shown that the formulations of these vaccines with carrier systems and adjuvants, obtain a specific immune response in the targeted area of the respiratory system. The recent studies focus on the formulation development of stable, non-invasive, dry powder inhaled vaccines that do not require cold chain storage and suitable for mass vaccination, also disposable devices which are suitable for this vaccines.

Anahtar Kelimeler

subunit vaccine, inhalable vaccine, pulmonary immunization

Kaynakça

• [1] T.C. Sağlık Bakanlığı Web site. (2018). Retrieved 22 July, 2020, https://asi.saglik.gov.tr/genel-bilgiler/41-asi-turleri.html
• [2] Dinc, G., Ulman, Y.I. (2007). The introduction of variolation “A La Turca” to the West by Lady Mary Montagu and Turkey’s contribution to this. Vaccine, 25 (21), 4261-4265.
• [3] Rappuoli, R. (2007). Bridging the knowledge gaps in vaccine design. Nature Biotechnology, 25, 1361-1366.
• [4] Clem, A.S. (2011). Fundamentals of vaccine immunology. Journal of Global Infectious Disease, 3, 73-78.
• [5] Wellington, K., Goa, K.L. (2003). Measles, mumps, rubella vaccine (PriorixTM; GSK-MMR): A review of its use in the prevention of measles, mumps and rubella. Drugs, 63, 2107-2126.
• [6] Kallerup, R.S., Foged, C. (2015). Classification of Vaccines. In: Foged C, Rades T, Perrie Y, Hook S, (Eds), Subunit Vaccine Delivery, (p.15). New York: Springer Science and Business Media.
• [7] Ferran, M.C., Skuse, G.R. (2017). Generation and Production of Modified Vaccinia Virus Ankara (MVA) as Vaccine Vector. In: Pavot V, Sebastian S, Turner V. A, Matthews J, Gilbert C.S (Eds), Recombinant Virus Vaccines, (pp. 97-119). New York: Springer Science and Business Media.
• [8] Van den Berg, J.H., Nuijen, B., Schumacher N.T., Haanen, B.A.G.J., Storm, G., Beijnen, H.J., Hennink, E.W. (2010). Synthetic vehicles for DNA vaccination. Journal of Drug Targeting, 18, 1-14.
• [9] Bins, A.D., van den Berg, J.H., Oosterhuis, K., Haanen, J.B.A.G. (2013). Recent advances towards the clinical application of DNA vaccines. Netherlands Journal of Medicine, 71, 109-117.
• [10] Powell, M.F., Newman, M.J. (1994). İmmunological and formulation design considerations for subunit vaccines. In: Powell, M.F., Newman, M.J. (Eds), Vaccine Design: The Subunit and Adjuvant Approach, (p.1). New York: Springer Science and Business Media.
• [11] Nevagi, R.J., Skwarczynski, M., Toth, I. (2019). Polymers for subunit vaccine delivery. European Polymer Journal, 114, 397-410.
• [12] O’Hagan, D.T., Friedland, L.R., Hanon, E., Didierlaurent, A.M. (2017). Towards an evidence based approach for the development of adjuvanted vaccines. Current Opinion in Immunology, 47, 93-102.
• [13] Foged, C. (2011). Subunit vaccines of the future: The need for safe, customized and optimized particulate delivery systems. Therapeutic Delivery, 2 (8), 1057-1077.
• [14] Bozkır, A., Hayta, G. (2004). Preparation and evaluation of multiple emülsions water-in-oil-in-water (w/o/w) as deliver system for influenza virus antigens. Journal of Drug Targeting, 12 (3), 157-164.
• [15] Sayın, B., Somavarapu, S., Li, X.W., Thanou, M., Sesardic, D., Alpar, H.O., Şenel, S. (2008). Mono-N-carboxymethyl chitosan (MCC) and N-trimethyl chitosan (TMC) nanoparticles for invasive vaccine delivery. International Journal of Pharmaceutics, 363 (1-2), 139-148.
• [16] Kaplan, M., Çelebi, N. (2014). Mukozal yoldan uygulanan aşı formülasyonlarının geliştirilmesi ve değerlendirilmesi. Gazi Üniversitesi Sağlık Bilimleri Enstitüsü Farmasötik Teknoloji Anabilim Dalı, Yüksek Lisans Tezi.
• [17] Awate, S., Babiuk, L.A., Mutwiri, G. (2013). Mechanisms of action of adjuvants. Frontiers in Immunology, 4, 114.
• [18] Gay, N.J., Gangloff, M. (2007). Structure and function of toll receptors and their ligands. Annual Review of Biochemistry, 76, 141-165.
• [19] Medzhitov, R. (2001). Toll-like receptors and innate immunity. Nature Reviews Immunology, 1, 135-145.
• [20] McKee, A.S., Marrack, P. (2017). Old and new adjuvants. Current Opinion in Immunology, 47, 44-51.
• [21] Del Giudice, G., Rappuoli, R., Didierlaurent, A.M. (2018). Correlates of adjuvanticity: A review on adjuvants in licensed vaccines. Seminars in Immunology, 39, 14-21.
• [22] Garçon, N., Chomez, P., Van Mechelen, M. (2007). GlaxoSmithKline Adjuvant Systems in vaccines: Concepts, achievements and perspectives. Expert Review of Vaccines, 6 (5), 723-739.
• [23] Schiller, J.T., Castellsagué, X., Villa, L.L., Hildesheim, A. (2008). An update of prophylactic human papillomavirus L1 virus-like particle vaccine clinical trial results. Vaccine, 26, K53-K61.
• [24] Şenel, S., Derici M.K. (2019). Aşı: Akademik,Endüstriyel ve Resmi Otorite Yönüyle. In: A. Bozkır and B. Devrim (Eds), Aşı Uygulama Yolları, (p.53). Ankara: Hipokrat Yayınevi.
• [25] Zhang, L., Wang, W., Wang, S. (2015). Effect of vaccine administration modality on immunogenicity and efficacy. Expert Review of Vaccines, 14 (11), 1509-1523.
• [26] Muttil, P., Pulliam, B., Garcia-Contreras, L., Fallon, J.K., Wang, C., Hickey, A.J., Edwards, A.D. (2010). Pulmonary immunization of guinea pigs with diphtheria CRM-197 antigen as nanoparticle aggregate dry powders enhance local and systemic immune responses. An Official Journal of the American Association of Pharmeceutical Scientists, 12 (4), 699-707.
• [27] Ballester, M., Nembrini, C., Dhar, N., de Titta, A., Piano, C., Pasquier, M., Simeoni, E., van der Vlies, A.J., McKinney, D.J., Hubbell, J.A., Swartz, M.A. (2011). Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis. Vaccine, 29 (40), 6959-6966.
• [28] Wong-Chew, R.M., Islas-Romero, R., García-García, M.D.L., Beeler, J.A., Audet, S., Santos-Preciado, J.I., Gans, H., Lew-Yasukawa, L., Maldonado, A.Y., Arvin, M.A., Valdespino-Gómez. L.J. (2006). Immunogenicity of aerosol measles vaccine given as the primary measles immunization to nine-month-old Mexican children. Vaccine, 24 (5), 683-690.
• [29] Sato, S., Kiyono, H. (2012). The mucosal immune system of the respiratory tract. Current Opinion in Virology, 2 (3), 225-232.
• [30] Yaghi, A., Dolovich, M. (2016). Airway Epithelial Cell Cilia and Obstructive Lung Disease. Cells, 5 (4), 40.
• [31] Martin, T.R., Frevert, C.W. (2005). Innate immunity in the lungs. Proceedings of the American Thoracic Society, 2 (5), 403-411.
• [32] Guilliams, M., Lambrecht, B.N., Hammad, H. (2013). Division of labor between lung dendritic cells and macrophages in the defense against pulmonary infections. Mucosal Immunology, 6 (3), 464-473.
• [33] Renegar, K.B., Small, P.A., Boykins, L.G., Wright, P.F. (2004). Role of IgA versus IgG in the Control of Influenza Viral Infection in the Murine Respiratory Tract. The Journal of Immunology, 173 (3), 1978-1986.
• [34] Kohlmeier, J.E., Woodland, D.L. (2009). Immunity to respiratory viruses. Annual Review of Immunology, 27, 61-82.
• [35] Blank, F., Stumbles, P., Von Garnier, C. (2011). Opportunities and challenges of the pulmonary route for vaccination. Expert Opinion on Drug Delivery, 8, 547-563.
• [36] Scheuch, G., Kohlhaeufl, J.M., Brand, P., Siekmeier, R. (2006). Clinical perspectives on pulmonary systemic and macromolecular delivery. Advanced Drug Delivery Reviews, 58, 996-1008.
• [37] Kunda, N.K., Somavarapu, S., Gordon, S.B., Hutcheon, G.A., Saleem, I.Y. (2013). Nanocarriers targeting dendritic cells for pulmonary vaccine delivery. Pharmaceutical Research, 30, 325-341.
• [38] Marasini, N., Kaminskas, L.M. (2019). Subunit-based mucosal vaccine delivery systems for pulmonary delivery - Are they feasible? Drug Development and Industrial Pharmacy, 45 (6), 882-894.
• [39] Minne, A., Louahed, J., Mehauden, S., Baras, B., Renauld, J.C., Vanbever, R. (2007). The delivery site of a monovalent influenza vaccine within the respiratory tract impacts on the immune response. Immunology, 122 (3), 316-325.
• [40] Todoroff, J., Ucakar, B., Inglese, M., Vandermarliere, S., Fillee, C., Renauld, J.C., Huygen, K., Vanbever, R. (2013). Targeting the deep lungs, Poloxamer 407 and a CpG oligonucleotide optimize immune responses to Mycobacterium tuberculosis antigen 85A following pulmonary delivery. European Journal of Pharmaceutics and Biopharmaceutics, 84 (1), 40-48.
• [41] Bachmann, F.M., Jennings, T.G. (2010). Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nature Reviews Immunology, 10, 787-796.
• [42] Kallerup, R.S., Foged, C. (2015). Pulmonary Administration of Subunit Vaccines. In: F.W. Tonnis, L.W.A. T. Huckriede, L.J.W. Hinrichs, W.H. Frijlink (Eds), Subunit Vaccine Delivery, (p.307). New York: Springer Science and Business Media.
• [43] Bennett, J. V., De Castro, J.F., Valdespino-Gomez, J.L., De Lourdes Garcia-Garcia, M., Islas-Romero, R., Echaniz-Aviles, G., Jimenez-Corona, A., Sepulveda-Amor, J. (2002). Aerosolized measles and measles-rubella vaccines induce better measles antibody booster responses than injected vaccines: Randomized trials in Mexican schoolchildren. Bulletin of the World Health Organization, 80 (10), 806-812.
• [44] Council of Europe, (2008). European Pharmacopoeia, 6th edn. Preparations for Inhalation (Ph Eur monograph 0671), (pp. 740–742). Strasbourg.
• [45] Khatri, L., Taylor, K.M.G., Craig, D.Q.M., Palin, K. (2001). An assessment of jet and ultrasonic nebulisers for the delivery of lactate dehydrogenase solutions. International Journal of Pharmaceutics, 227, 121-131.
• [46] Tonnis, W.F., Lexmond, A.J., Frijlink, H.W., De Boer, A.H., Hinrichs, W.L.J. (2013). Devices and formulations for pulmonary vaccination. Expert Opinion on Drug Delivery, 10 (10), 1383-1397.
• [47] Smyth, H.D.C. (2005). Propellant-driven metered-dose inhalers for pulmonary drug delivery. Expert Opinion on Drug Delivery, 2 (1), 53-74.
• [48] Tonnis, W.F., Kersten, G.F., Frijlink, H.W., Hinrichs, W.L.J., De Boer, A.H., Amorij, J.P. (2012). Pulmonary vaccine delivery: A realistic approach? Journal of Aerosol Medicine and Pulmonary Drug Delivery, 25 (5), 249-260.
• [49] Frijlink, H.W., De Boer, A.H. (2004). Dry powder inhalers for pulmonary drug delivery. Expert Opinion on Drug Delivery, 1 (1), 67-86.
• [50] Sou, T., Morton, D.A.V., Williamson, M., Meeusen, E.N., Kaminskas, L.M., Mclntosh, P.M. (2015). Spray-dried influenza antigen with trehalose and leucine produces an aerosolizable powder vaccine formulation that ınduces strong systemic and mucosal ımmunity after pulmonary administration. Journal of Aerosol Medicine and Pulmonary Drug Delivery, 28 (5), 361-371.
• [51] Saluja, V., Amorij, J.P., Kapteyn, J.C., de Boer, A.H., Frijlink H.W., Hinrichs, W.L.J. (2010). A comparison between spray drying and spray freeze drying to produce an influenza subunit vaccine powder for inhalation. Journal of Controlled Release, 144 (2), 127-133.
• [52] Thakur, A., Ingvarsson, P.T., Schmidt, S.T., Rose, F., Andersen, P., Christensen, D., Foged, C. (2018). Immunological and physical evaluation of the multistage tuberculosis subunit vaccine candidate H56/CAF01 formulated as a spray-dried powder. Vaccine, 36 (23), 3331-3339.
• [53] Lin, W.H., Griffin, D.E., Rota, P.A., Papania, M., Cape, P.S., Bennett, D., Quinn, B., Sievers, E.R., Shermer, C., Powell, K., Adams, J.R., Godin, S., Winston, S. (2011). Successful respiratory immunization with dry powder live-attenuated measles virus vaccine in rhesus macaques. Proceedings of the National Academy of Sciences of the United States of America, 108 (7), 2987-2992.
• [54] Lu, D., Garcia-Contreras, L., Muttil, P., Padilla, D., Xu, D., Liu, J., Braunstein, M., McMurray, D.N., Hickey, A.J. (2010). Pulmonary immunization using antigen 85-b polymeric microparticles to boost tuberculosis immunity. An Official Journal of the American Association of Pharmeceutical Scientists, 12 (3), 338-347.
• [55] Eyles, J.E., Williamson, E.D., Spiers, I.D., Alpar, H.O. (2000). Protection studies following bronchopulmonary and intramuscular immunisation with yersinia pestis F1 and V subunit vaccines coencapsulated in biodegradable microspheres. Vaccine, 18 ( 28), 3266-3271.
• [56] Muttil, P., Prego, C., Garcia-Contreras, L., Pulliam, B., Fallon, J.K., Wang, C., Hickey, J.A., Edwards, D. (2010). Immunization of guinea pigs with novel hepatitis B antigen as nanoparticle aggregate powders administered by the pulmonary route. An Official Journal of the American Association of Pharmeceutical Scientists, 12, 330-337.
• [57] Thomas, C., Gupta, V., Ahsan, F. (2010). Particle size influences the immune response produced by hepatitis B vaccine formulated in inhalable particles. Pharmaceutical Research, An Official Journal of the American Association of Pharmeceutical Scientists, 27, 905-919.
• [58] Thomas, C., Rawat, A., Hope-Weeks, L., Ahsan, F. (2011). Aerosolized PLA and PLGA nanoparticles enhance humoral, mucosal and cytokine responses to hepatitis B vaccine. Molecular Pharmaceutics, 8, 405-415.
• [59] Amorij, J-P., Saluja, V., Petersen, H., Hinrichs, W.L.J., Huckriede, A., Frijlink, H.W. (2007). Pulmonary delivery of an inulin-stabilized influenza subunit vaccine prepared by spray-freeze drying induces systemic, mucosal humoral as well as cell-mediated immune responses in BALB/c mice. Vaccine, 25 (52), 8707-8717.
• [60] Wee, J.L.K., Scheerlinck, J-P.Y., Snibson, K.J., Edwards, S., Pearse, M., Quinn, C., Sutton, P. (2008). Pulmonary delivery of ISCOMATRIX influenza vaccine induces both systemic and mucosal immunity with antigen dose sparing. Mucosal Immunology, 1 (6) , 489-96.
• [61] White, A.D., Sibley, L., Dennis, M.J., Gooch, K., Betts, G., Edwards, N., Reyes-Sandoval, A., Carroll, M.W., Williams, A., Marsh, P.D. (2013). Evaluation of the safety and immunogenicity of a candidate tuberculosis vaccine, MVA85A, delivered by aerosol to the lungs of macaques. Clinical and Vaccine Immunology, 20 (5) , 663-72.
• [62] Amidi, M., Pellikaan, H.C., Hirschberg, H., Boer, H.A., Crommelin, J.A.D., Hennink, E.W., Kersten, G., Jiskoot, W. (2007). Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination: preparation, characterization and evaluation in guinea pigs. Vaccine, 25, 6818–6829.
• [63] Smith, D.J., Bot, S., Dellamary, L., Bot, A. (2003). Evaluation of novel aerosol formulations designed for mucosal vaccination against influenza virus. Vaccine, 21, 2805–2812.
• [64] Tomara, J., Tonnis W.F., Patil H.P., Boer A.H., Hagedoorna, P., Vanbeverb, R., Frijlink, H.W., Hinrichsa, L.J.W. (2019). Pulmonary immunization: deposition site is of minor relevance for influenza vaccination but deep lung deposition is crucial for hepatitis B vaccination. Acta Pharmaceutica Sinica B, 9 (6), 1231-1240.