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Virus Benzeri Partiküller ve Aşıların Geliştirilmesinde Önemi

Yıl 2022, Cilt: 15 Sayı: 1, 88 - 94, 30.04.2022

Buket Gül Feray Alkan

https://doi.org/10.52976/vansaglik.908047

Öz

Aşı, hem insanlarda hem de hayvanlarda patojen mikroorganizmaları kontrol etme ve hastalıkları önlemede en etkili yol olarak kullanılan biyolojik maddedir. Hayvanların viral hastalıklarına karşı kullanılan geleneksel aşılar, inaktive edilmiş veya zayıflatılmış virus aşılarından oluşmaktadır. Ancak son yıllarda mikroorganizmaların alt ünitelerini içeren aşılara yönelik çalışmalar dikkat çekicidir. Bunlardan “Virus Benzeri Parçacık” (Virus Like Particle, VLP) aşıları, aşı kavramına farklı sınırlar açan yaklaşımlardan birini temsil eder. Kapsit yapısından oluşan, virus genomu içermeyen bu yapılar otantik virionun doğal konfigürasyonunu taklit ederek hem humoral hem de hücreye bağlı bağışıklık tepkilerini etkili bir şekilde ortaya çıkarır. VLP’ler taklit ettikleri hedef antijene karşı immun sistemi uyarmalarının yanı sıra farklı antijenler için taşıyıcılık yaparak da aşıların geliştirilmesine katkı sağlarlar. Bu derlemede VLP’lerin genel özellikleri, immun sistemi uyarma mekanizmaları, üretimleri ve VLP içeren aşı geliştirme teknolojisinin potansiyel avantajları ve olası sınırlamalardan bahsedilmektedir.

Anahtar Kelimeler

Aşı virus virus benzeri partikül (VLP)

Kaynakça

  • Aires KA, Cianciarullo AM, Carneiro SM, Villa LL, Boccardo E, Pérez-Martinez G et al. Production of human papillomavirus type 16 L1 virus-like particles by recombinant Lactobacillus casei cells. Applied and environmental microbiology 2006;72(1), 745-752.
  • Arevalo MT, Wong TM, Ross TM. Expression and purification of virus-like particles for vaccination. JoVE (Journal of Visualized Experiments) 2016;112, e54041.
  • Boigard H, Alımova A, Martin GR, Katz A, Gottlieb P, Galarza JM. Zika virus-like particle (VLP) based vaccine. PLoS neglected tropical diseases 2017;11(5), e0005608.
  • Brun A, Bárcena J, Blanco E, Borrego B, Dory D, Escribano JM et al. Current strategies for subunit and genetic viral veterinary vaccine development. Virus research 2011;157(1), 1-12.
  • Cao Y, Lu Z, Sun J, Bai X, Sun P, Bao H et al. Synthesis of empty capsid-like particles of Asia I foot-and-mouth disease virus in insect cells and their immunogenicity in guinea pigs. Veterinary microbiology 2009;137(1-2), 10-17.
  • Changotra, H, Vıj, A. Rotavirus virus‐like particles (RV‐VLPs) vaccines: An update. Reviews in medical virology 2017;27(6), e1954.
  • Chen Q, Lai H. Plant-derived virus-like particles as vaccines. Human vaccines & immunotherapeutics 2013;9(1), 26-49.
  • Cox MM. Recombinant protein vaccines produced in insect cells. Vaccine 2012;30(10), 1759-1766.
  • Crisci E, Bárcena J, Montoya M. Virus-like particles: the new frontier of vaccines for animal viral infections. Veterinary immunology and immunopathology 2012;148(3-4), 211-225.
  • Di Martino B, Marsilio F. Feline calicivirus VP2 is involved in the self-assembly of the capsid protein into virus-like particles. Research in veterinary science 2010;89(2), 279-281.
  • Du J, Ährlund Rıchter A, Näsman A, Dalıanis T. Human papilloma virus (HPV) prevalence upon HPV vaccination in Swedish youth: a review based on our fndings 2008–2018, and perspectives on cancer prevention. Archives of Gynecology and Obstetrics 2021;303:329–335.
  • Evans TG, Bonnez W, Rose RC, Koenig S, Demeter L, Suzich JA et al. A Phase 1 study of a recombinant virus like particle vaccine against human papillomavirus type 11 in healthy adult volunteers. The Journal of infectious diseases 2001;183(10), 1485-1493.
  • Fontana D, Kratje R, Etcheverrigaray M, Prieto C. Rabies virus-like particles expressed in HEK293 cells. Vaccine 2014;32 :2799-2804
  • French TJ, Marshall JJ, Roy P. Assembly of double-shelled, virus like particles of bluetongue virus by the simultaneous expression of four structural proteins. Journal of virology 1990;64(12), 5695-5700.
  • Fuenmayor J, Cervera L, Gutiérrez-Granados S, Gòdia F. Transient gene expression optimization and expression vector comparison to improve HIV-1 VLP production in HEK293 cell lines. Applied microbiology and biotechnology 2018;102(1), 165-174.
  • Fuenmayor J, Gòdia F, Cervera L. Production of virus-like particles for vaccines. New biotechnology 2017;39,174-180.
  • Gamvrellis A, Leong D, Hanley JC, Xiang SD, Mottram P, Plebanski M. Vaccines that facilitate antigen entry into dendritic cells. Immunology and cell biology 2004;82(5), 506-516.
  • Grgacic EV, Anderson DA. Virus-like particles: passport to immune recognition. Methods 2006;40(1), 60-65.
  • Hinkula J, Devignot S, Åkerstrom S, Karlberg H, Wattrang E, Bereczky S et al. Immunization with DNA plasmids coding for Crimean-Congo hemorrhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice. Journal of virology 2017;91(10).
  • Hu Yc, Bentley We. Effect of MOI ratio on the composition and yield of chimeric infectious bursal disease virus-like particles by baculovirus co-infection: Deterministic predictions and experimental results. Biotechnol. Bioeng 2001;75,104-119.
  • Iqbal Yatoo M, Hamid Z, Parray O, Wani A, Ul Haq A, Saxena A. COVID-19 Recent advancements in identifying novel vaccine candidates and current status of upcoming SARS-CoV-2 vaccines. Human Vaccines & Immunotherapeutics 2020;1-14.
  • Jennings GT, Bachmann MF. The coming of age of virus-like particle vaccines. Biological chemistry 2008;389(5), 521-536.
  • Ji, P, Liu Y, Chen Y, Wang A, Jıang D, Zhao B, Zhang G. Porcine parvovirus capsid protein expressed in Escherichia coli self-assembles into virus-like particles with high immunogenicity in mice and guinea pigs. Antiviral research 2017;139, 146-152.
  • Johnson RF, Bell P, Harty RN. Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology. Virology journal 2006;3(1), 1-7.
  • Ko Y, Kang S, Nah J, Paton D, Oem J, Wilsden G et al. Noninfectious virus-like particle antigen for detection of swine vesicular disease virus antibodies in pigs by enzyme-linked immunosorbent assay, Clinical and diagnostic laboratory immunology, 2005;12(8), 922-929.
  • Krammer F, Schinko T, Palmberger D, Tauer C, Messner P, Grabher R. Trichoplusiani cells (High Five TM) are highly efficient for the production of influenza A virus-like particles: a comparison of two insect cell lines as production platforms for influenza vaccines. Mol. Biotechnol 2010;45, 226-234.
  • Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nature reviews Drug discovery 2006;5(6), 471-484.
  • Latham T, Galarza JM. Formation of wild-type and chimeric influenza virus-like particles following simultaneous expression of only four structural proteins. Journal of virology 2001;75(13), 6154-6165.
  • Lee DH, Park JK, Lee YN, Song JM, Kang SM, Lee JB et al. H9N2 avian influenza virus-like particle vaccine provides protective immunity and a strategy for the differentiation of infected from vaccinated animals. Vaccine 2011;29(23), 4003-4007.
  • Liu F, Ge S, Li L, Wu X, Liu Z, Wang Z. Virus-like particles: potential veterinary vaccine immunogens. Research in veterinary science 2012;93(2), 553-559.
  • McGinnes W, Pantua H, Laliberte JP, Gravel KA, Jain S, Morrison TG. Assembly and biological and immunological properties of Newcastle disease virus-like particles. Journal of virology 2010;84(9), 4513-4523.
  • Mohsen MO, Zha L, Cabral-Miranda G, Bachmann MF. Major findings and recent advances in virus–like particle (VLP)-based vaccines. In Seminars in immunology 2017;34,123-132.
  • Mortola E, Roy P. Efficient assembly and release of SARS coronavirus-like particles by a heterologous expression system. FEBS letters 2004;576, 174-178.
  • Noad R, Roy P (2003). Virus-like particles as immunogens. Trends in microbiology 2003;11(9),438-444.
  • Pillay S, Meyers A, Williamson A, Rybicki E. 2009. Optimization of chimeric HIV-1 virus-like particle production in a baculovirus- insect cell expression system. Biotechnology progress 2009;25(4),1153-1160.
  • Plummer EM, Manchester M. Viral nanoparticles and virus‐like particles: platforms for contemporary vaccine design. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2011;3(2), 174-196.
  • Roy P, Noad R. Virus like particles as a vaccine delivery system: Myths and facts. Human vaccines 2008;4(1), 5-12.
  • Saraswat S, Athmaram TN, Parıda M, Agarwal A, Saha A, Dash PK. Expression and characterization of yeast derived chikungunya virus like particles (CHIK-VLPs) and its evaluation as a potential vaccine candidate. PLoS neglected tropical diseases 2016;10(7),e0004782.
  • Sasnauskas K, Bulavaıte A, Hale A, Jın L, Knowles W, Gedvılaıte A. Generation of recombinant virus-like particles of human and non-human polyomaviruses in yeast Saccharomyces cerevisiae. Intervirology 2002;45, 308-317.
  • Stewart M, Bhatia Y, Athmaran TN, Noad R, Gastaldi C, Dubois E et al. Validation of a novel approach for the rapid production of immunogenic virus-like particles for bluetongue virus. Vaccine 2010;28(17), 3047-3054.
  • Stewart M, Dovas C, Chatzinasiou E, Athmaram TN, Papanastassopoulou M, Papadopoulos O. Protective efficacy of Bluetongue virus-like and subvirus-like particles in sheep: presence of the serotype-specific VP2, independent of its geographic lineage, is essential for protection. Vaccine 2012;30(12), 2131-2139.
  • Stewart M, Dubois E, Sailleau C, Bréard E, Viarouge C, Desprat A et al. Bluetongue virus serotype 8 virus-like particles protect sheep against virulent virus infection as a single or multi-serotype cocktail immunogen. Vaccine 2013;31(3), 553-558.
  • Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. The Journal of Immunology 2004;172(3), 1777-1785.
  • Tan M, Zhong W, Song D, Thornton S, Jiang X. E. coli‐expressed recombinant norovirus capsid proteins maintain authentic antigenicity and receptor binding capability. Journal of medical virology 2004;74(4), 641-649.
  • Thompson CM, Petiot E, Lennaertz A, Henry O, Kamen AA. Analytical technologies for influenza virus-like particle candidate vaccines: challenges and emerging approaches. Virology journal 2013;10(1), 141.
  • Thompson CM, Petiot E, Mullick A, Aucoin MG, Henry O, Kamen AA. Critical assessment of influenza VLP production in Sf9 and HEK293 expression systems. BMC biotechnology 2015;15(1), 1-12.
  • Van Oers MM. Opportunities and challenges for the baculovirus expression system. Journal of invertebrate pathology 2011;107, S3-S15.
  • Warzecha H, Mason H, Lane C, Tryggvesson A, Rybıckı E, Wıllıamson A, Clements Jd, Rose R. Oral immunogenicity of human papillomavirus-like particles expressed in potato. Journal of virology 2003;77(16), 8702-8711.
  • Wi GR, Hwang JY, Kwon MG, Kim HJ, Kang HA, Kim HJ. Protective immunity against nervous necrosis virus in convict grouper Epinephelus septemfasciatus following vaccination with virus-like particles produced in yeast Saccharomyces cerevisiae. Veterinary microbiology 2015;177(1-2), 214-218.
  • Xu R, Shi M, Li J, Song P, Li N. (2020) Construction of SARS-CoV-2 Virus-Like Particles by Mammalian Expression System. Frontiers in bioengineering and biotechnology 2020; doi: 10.3389/fbioe.2020.00862
  • Yan F, Li E, Li L, Schiffman Z, Huang P, Zhang S. Virus-Like Particles Derived From a Virulent Strain of Pest des Petits Ruminants Virus Elicit a More Vigorous Immune Response in Mice and Small Ruminants Than Those From a Vaccine Strain. Frontiers in microbiology 2020; doi: 10.3389/fmicb.2020.00609

Yıl 2022, Cilt: 15 Sayı: 1, 88 - 94, 30.04.2022

Buket Gül Feray Alkan

https://doi.org/10.52976/vansaglik.908047

Öz

Kaynakça

  • Aires KA, Cianciarullo AM, Carneiro SM, Villa LL, Boccardo E, Pérez-Martinez G et al. Production of human papillomavirus type 16 L1 virus-like particles by recombinant Lactobacillus casei cells. Applied and environmental microbiology 2006;72(1), 745-752.
  • Arevalo MT, Wong TM, Ross TM. Expression and purification of virus-like particles for vaccination. JoVE (Journal of Visualized Experiments) 2016;112, e54041.
  • Boigard H, Alımova A, Martin GR, Katz A, Gottlieb P, Galarza JM. Zika virus-like particle (VLP) based vaccine. PLoS neglected tropical diseases 2017;11(5), e0005608.
  • Brun A, Bárcena J, Blanco E, Borrego B, Dory D, Escribano JM et al. Current strategies for subunit and genetic viral veterinary vaccine development. Virus research 2011;157(1), 1-12.
  • Cao Y, Lu Z, Sun J, Bai X, Sun P, Bao H et al. Synthesis of empty capsid-like particles of Asia I foot-and-mouth disease virus in insect cells and their immunogenicity in guinea pigs. Veterinary microbiology 2009;137(1-2), 10-17.
  • Changotra, H, Vıj, A. Rotavirus virus‐like particles (RV‐VLPs) vaccines: An update. Reviews in medical virology 2017;27(6), e1954.
  • Chen Q, Lai H. Plant-derived virus-like particles as vaccines. Human vaccines & immunotherapeutics 2013;9(1), 26-49.
  • Cox MM. Recombinant protein vaccines produced in insect cells. Vaccine 2012;30(10), 1759-1766.
  • Crisci E, Bárcena J, Montoya M. Virus-like particles: the new frontier of vaccines for animal viral infections. Veterinary immunology and immunopathology 2012;148(3-4), 211-225.
  • Di Martino B, Marsilio F. Feline calicivirus VP2 is involved in the self-assembly of the capsid protein into virus-like particles. Research in veterinary science 2010;89(2), 279-281.
  • Du J, Ährlund Rıchter A, Näsman A, Dalıanis T. Human papilloma virus (HPV) prevalence upon HPV vaccination in Swedish youth: a review based on our fndings 2008–2018, and perspectives on cancer prevention. Archives of Gynecology and Obstetrics 2021;303:329–335.
  • Evans TG, Bonnez W, Rose RC, Koenig S, Demeter L, Suzich JA et al. A Phase 1 study of a recombinant virus like particle vaccine against human papillomavirus type 11 in healthy adult volunteers. The Journal of infectious diseases 2001;183(10), 1485-1493.
  • Fontana D, Kratje R, Etcheverrigaray M, Prieto C. Rabies virus-like particles expressed in HEK293 cells. Vaccine 2014;32 :2799-2804
  • French TJ, Marshall JJ, Roy P. Assembly of double-shelled, virus like particles of bluetongue virus by the simultaneous expression of four structural proteins. Journal of virology 1990;64(12), 5695-5700.
  • Fuenmayor J, Cervera L, Gutiérrez-Granados S, Gòdia F. Transient gene expression optimization and expression vector comparison to improve HIV-1 VLP production in HEK293 cell lines. Applied microbiology and biotechnology 2018;102(1), 165-174.
  • Fuenmayor J, Gòdia F, Cervera L. Production of virus-like particles for vaccines. New biotechnology 2017;39,174-180.
  • Gamvrellis A, Leong D, Hanley JC, Xiang SD, Mottram P, Plebanski M. Vaccines that facilitate antigen entry into dendritic cells. Immunology and cell biology 2004;82(5), 506-516.
  • Grgacic EV, Anderson DA. Virus-like particles: passport to immune recognition. Methods 2006;40(1), 60-65.
  • Hinkula J, Devignot S, Åkerstrom S, Karlberg H, Wattrang E, Bereczky S et al. Immunization with DNA plasmids coding for Crimean-Congo hemorrhagic fever virus capsid and envelope proteins and/or virus-like particles induces protection and survival in challenged mice. Journal of virology 2017;91(10).
  • Hu Yc, Bentley We. Effect of MOI ratio on the composition and yield of chimeric infectious bursal disease virus-like particles by baculovirus co-infection: Deterministic predictions and experimental results. Biotechnol. Bioeng 2001;75,104-119.
  • Iqbal Yatoo M, Hamid Z, Parray O, Wani A, Ul Haq A, Saxena A. COVID-19 Recent advancements in identifying novel vaccine candidates and current status of upcoming SARS-CoV-2 vaccines. Human Vaccines & Immunotherapeutics 2020;1-14.
  • Jennings GT, Bachmann MF. The coming of age of virus-like particle vaccines. Biological chemistry 2008;389(5), 521-536.
  • Ji, P, Liu Y, Chen Y, Wang A, Jıang D, Zhao B, Zhang G. Porcine parvovirus capsid protein expressed in Escherichia coli self-assembles into virus-like particles with high immunogenicity in mice and guinea pigs. Antiviral research 2017;139, 146-152.
  • Johnson RF, Bell P, Harty RN. Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology. Virology journal 2006;3(1), 1-7.
  • Ko Y, Kang S, Nah J, Paton D, Oem J, Wilsden G et al. Noninfectious virus-like particle antigen for detection of swine vesicular disease virus antibodies in pigs by enzyme-linked immunosorbent assay, Clinical and diagnostic laboratory immunology, 2005;12(8), 922-929.
  • Krammer F, Schinko T, Palmberger D, Tauer C, Messner P, Grabher R. Trichoplusiani cells (High Five TM) are highly efficient for the production of influenza A virus-like particles: a comparison of two insect cell lines as production platforms for influenza vaccines. Mol. Biotechnol 2010;45, 226-234.
  • Krieg AM. Therapeutic potential of Toll-like receptor 9 activation. Nature reviews Drug discovery 2006;5(6), 471-484.
  • Latham T, Galarza JM. Formation of wild-type and chimeric influenza virus-like particles following simultaneous expression of only four structural proteins. Journal of virology 2001;75(13), 6154-6165.
  • Lee DH, Park JK, Lee YN, Song JM, Kang SM, Lee JB et al. H9N2 avian influenza virus-like particle vaccine provides protective immunity and a strategy for the differentiation of infected from vaccinated animals. Vaccine 2011;29(23), 4003-4007.
  • Liu F, Ge S, Li L, Wu X, Liu Z, Wang Z. Virus-like particles: potential veterinary vaccine immunogens. Research in veterinary science 2012;93(2), 553-559.
  • McGinnes W, Pantua H, Laliberte JP, Gravel KA, Jain S, Morrison TG. Assembly and biological and immunological properties of Newcastle disease virus-like particles. Journal of virology 2010;84(9), 4513-4523.
  • Mohsen MO, Zha L, Cabral-Miranda G, Bachmann MF. Major findings and recent advances in virus–like particle (VLP)-based vaccines. In Seminars in immunology 2017;34,123-132.
  • Mortola E, Roy P. Efficient assembly and release of SARS coronavirus-like particles by a heterologous expression system. FEBS letters 2004;576, 174-178.
  • Noad R, Roy P (2003). Virus-like particles as immunogens. Trends in microbiology 2003;11(9),438-444.
  • Pillay S, Meyers A, Williamson A, Rybicki E. 2009. Optimization of chimeric HIV-1 virus-like particle production in a baculovirus- insect cell expression system. Biotechnology progress 2009;25(4),1153-1160.
  • Plummer EM, Manchester M. Viral nanoparticles and virus‐like particles: platforms for contemporary vaccine design. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 2011;3(2), 174-196.
  • Roy P, Noad R. Virus like particles as a vaccine delivery system: Myths and facts. Human vaccines 2008;4(1), 5-12.
  • Saraswat S, Athmaram TN, Parıda M, Agarwal A, Saha A, Dash PK. Expression and characterization of yeast derived chikungunya virus like particles (CHIK-VLPs) and its evaluation as a potential vaccine candidate. PLoS neglected tropical diseases 2016;10(7),e0004782.
  • Sasnauskas K, Bulavaıte A, Hale A, Jın L, Knowles W, Gedvılaıte A. Generation of recombinant virus-like particles of human and non-human polyomaviruses in yeast Saccharomyces cerevisiae. Intervirology 2002;45, 308-317.
  • Stewart M, Bhatia Y, Athmaran TN, Noad R, Gastaldi C, Dubois E et al. Validation of a novel approach for the rapid production of immunogenic virus-like particles for bluetongue virus. Vaccine 2010;28(17), 3047-3054.
  • Stewart M, Dovas C, Chatzinasiou E, Athmaram TN, Papanastassopoulou M, Papadopoulos O. Protective efficacy of Bluetongue virus-like and subvirus-like particles in sheep: presence of the serotype-specific VP2, independent of its geographic lineage, is essential for protection. Vaccine 2012;30(12), 2131-2139.
  • Stewart M, Dubois E, Sailleau C, Bréard E, Viarouge C, Desprat A et al. Bluetongue virus serotype 8 virus-like particles protect sheep against virulent virus infection as a single or multi-serotype cocktail immunogen. Vaccine 2013;31(3), 553-558.
  • Storni T, Ruedl C, Schwarz K, Schwendener RA, Renner WA, Bachmann MF. Nonmethylated CG motifs packaged into virus-like particles induce protective cytotoxic T cell responses in the absence of systemic side effects. The Journal of Immunology 2004;172(3), 1777-1785.
  • Tan M, Zhong W, Song D, Thornton S, Jiang X. E. coli‐expressed recombinant norovirus capsid proteins maintain authentic antigenicity and receptor binding capability. Journal of medical virology 2004;74(4), 641-649.
  • Thompson CM, Petiot E, Lennaertz A, Henry O, Kamen AA. Analytical technologies for influenza virus-like particle candidate vaccines: challenges and emerging approaches. Virology journal 2013;10(1), 141.
  • Thompson CM, Petiot E, Mullick A, Aucoin MG, Henry O, Kamen AA. Critical assessment of influenza VLP production in Sf9 and HEK293 expression systems. BMC biotechnology 2015;15(1), 1-12.
  • Van Oers MM. Opportunities and challenges for the baculovirus expression system. Journal of invertebrate pathology 2011;107, S3-S15.
  • Warzecha H, Mason H, Lane C, Tryggvesson A, Rybıckı E, Wıllıamson A, Clements Jd, Rose R. Oral immunogenicity of human papillomavirus-like particles expressed in potato. Journal of virology 2003;77(16), 8702-8711.
  • Wi GR, Hwang JY, Kwon MG, Kim HJ, Kang HA, Kim HJ. Protective immunity against nervous necrosis virus in convict grouper Epinephelus septemfasciatus following vaccination with virus-like particles produced in yeast Saccharomyces cerevisiae. Veterinary microbiology 2015;177(1-2), 214-218.
  • Xu R, Shi M, Li J, Song P, Li N. (2020) Construction of SARS-CoV-2 Virus-Like Particles by Mammalian Expression System. Frontiers in bioengineering and biotechnology 2020; doi: 10.3389/fbioe.2020.00862
  • Yan F, Li E, Li L, Schiffman Z, Huang P, Zhang S. Virus-Like Particles Derived From a Virulent Strain of Pest des Petits Ruminants Virus Elicit a More Vigorous Immune Response in Mice and Small Ruminants Than Those From a Vaccine Strain. Frontiers in microbiology 2020; doi: 10.3389/fmicb.2020.00609
Toplam 51 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Veteriner Cerrahi
Bölüm Derleme
Yazarlar

Buket Gül 0000-0001-6584-8916

Feray Alkan 0000-0003-3854-6503

Yayımlanma Tarihi 30 Nisan 2022
Gönderilme Tarihi 2 Nisan 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 15 Sayı: 1

Kaynak Göster

APA Gül, B., & Alkan, F. (2022). Virus Benzeri Partiküller ve Aşıların Geliştirilmesinde Önemi. Van Sağlık Bilimleri Dergisi, 15(1), 88-94. https://doi.org/10.52976/vansaglik.908047
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