Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Comparative Biodistribution Study of Baculoviral and Adenoviral Vector Vaccines against SARS-CoV-2

  • Hyeon Dong Lee (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Jungmin Chun (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Sehyun Kim (KR BioTech Co. Ltd.) ;
  • Nowakowska Aleksandra (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Chanyeong Lee (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Doyoung Yoon (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Hee-jung Lee (Department of Biomedical Science and Engineering, Konkuk University) ;
  • Young Bong Kim (Department of Biomedical Science and Engineering, Konkuk University)
  • Received : 2023.08.23
  • Accepted : 2023.09.27
  • Published : 2024.01.28
Download PDF
⟨ Previous Next ⟩

Abstract

Various types of vaccines have been developed against COVID-19, including vector vaccines. Among the COVID-19 vaccines, AstraZeneca's chimpanzee adenoviral vaccine was the first to be commercialized. For viral vector vaccines, biodistribution studies are critical to vaccine safety, gene delivery, and efficacy. This study compared the biodistribution of the baculoviral vector vaccine (AcHERV-COVID19) and the adenoviral vector vaccine (Ad-COVID19). Both vaccines were administered intramuscularly to mice, and the distribution of the SARS-CoV-2 S gene in each tissue was evaluated for up to 30 days. After vaccination, serum and various tissue samples were collected from the mice at each time point, and IgG levels and DNA copy numbers were measured using an enzyme-linked immunosorbent assay and a quantitative real-time polymerase chain reaction. AcHERV-COVID19 and Ad-COVID19 distribution showed that the SARS-CoV-2 spike gene remained predominantly at the injection site in the mouse muscle. In kidney, liver, and spleen tissues, the AcHERV-COVID19 group showed about 2-4 times higher persistence of the SARS-CoV-2 spike gene than the Ad-COVID19 group. The distribution patterns of AcHERV-COVID19 and Ad-COVID19 within various organs highlight their contrasting biodistribution profiles, with AcHERV-COVID19 exhibiting a broader and prolonged presence in the body compared to Ad-COVID19. Understanding the biodistribution profile of AcHERV-COVID19 and Ad-COVID19 could help select viral vectors for future vaccine development.

Keywords

Acknowledgement

This research was supported by a grant (22183MFDS443) from the Ministry of Food and Drug Safety and the Korean Health Technology R&D Project (No. HV23C0074 and HV22C0263).

References

  1. Kyriakidis NC, Lopez-Cortes A, Gonzalez EV, Grimaldos AB, Prado EO. 2021. SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates. NPJ Vaccines 6: 28. 
  2. Travieso T, Li J, Mahesh S, Mello J, Blasi M. 2022. The use of viral vectors in vaccine development. NPJ Vaccines 7: 75. 
  3. Deng S, Liang H, Chen P, Li Y, Li Z, Fan S, et al. 2022. Viral vector vaccine development and application during the COVID-19 pandemic. Microorganisms 10: 1450. 
  4. Lundstrom K. 2021. Viral vectors for COVID-19 vaccine development. Viruses 13: 317. 
  5. McCann N, O'Connor D, Lambe T, Pollard AJ. 2022. Viral vector vaccines. Curr. Opin. Immunol. 77: 102210. 
  6. Jang Y, Cho H, Chun J, Park K, Nowakowska A, Kim J, et al. 2023. Baculoviral COVID-19 Delta DNA vaccine cross-protects against SARS-CoV2 variants in K18-ACE2 transgenic mice. Vaccine 41: 1223-1231. 
  7. Cho H, Jang Y, Park KH, Choi H, Nowakowska A, Lee HJ, et al. 2021. Human endogenous retrovirus-enveloped baculoviral DNA vaccines against MERS-CoV and SARS-CoV2. NPJ. Vaccines 6: 37. 
  8. Gwon YD, Kim S, Cho Y, Heo Y, Cho H, Park K, et al. 2016. Immunogenicity of virus like particle forming baculoviral DNA vaccine against pandemic influenza H1N1. PLoS One 11: e0154824. 
  9. Naasani I. 2022. Establishing the pharmacokinetics of genetic vaccines is essential for maximising their safety and efficacy. Clin. Pharmacokinet. 61: 921-927. 
  10. Shimada M, Wang H, Ichino M, Ura T, Mizuki N, Okuda K. 2022. Biodistribution and immunity of adenovirus 5/35 and modified vaccinia Ankara vector vaccines against human immunodeficiency virus 1 clade C. Gene Ther. 29: 636-642. 
  11. Li LH, Liesenborghs L, Wang L, Lox M, Yakass MB, Jansen S, et al. 2022. Biodistribution and environmental safety of a live-attenuated YF17D-vectored SARS-CoV-2 vaccine candidate. Mol. Ther. Methods Clin. Dev. 25: 215-224. 
  12. Stebbings R, Armour G, Pettis V, Goodman J. 2022. AZD1222 (ChAdOx1 nCov-19): A single-dose biodistribution study in mice. Vaccine 40: 192-195. 
  13. Sheets RL, Stein J, Bailer RT, Koup RA, Andrews C, Nason M, et al. 2008. Biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (HIV-1), Ebola, or Marburg are similar despite differing adenovirus serotype vector, manufacturer's construct, or gene inserts. J. Immunotoxicol. 5: 315-335. 
  14. Yang R, Deng Y, Huang B, Huang L, Lin A, Li Y, et al. 2021. A core-shell structured COVID-19 mRNA vaccine with favorable biodistribution pattern and promising immunity. Signal Transduct. Target. Ther. 6: 213. 
  15. Driedonks T, Jiang L, Carlson B, Han Z, Liu G, Queen SE, et al. 2022. Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina. J. Extracell. Biol. 1: e59. 
  16. Pan D, Gunther R, Duan W, Wendell S, Kaemmerer W, Kafri T, et al. 2002. Biodistribution and toxicity studies of VSVG-pseudotyped lentiviral vector after intravenous administration in mice with the observation of in vivo transduction of bone marrow. Mol. Ther. 6: 19-29. 
  17. Kang M, Jordan V, Blenkiron C, Chamley LW. 2021. Biodistribution of extracellular vesicles following administration into animals: a systematic review. J. Extracell. Vesicles 10: e12085. 
  18. Wang L, Rao Y, Liu X, Sun L, Gong J, Zhang H, et al. 2021. Administration route governs the therapeutic efficacy, biodistribution and macrophage targeting of anti-inflammatory nanoparticles in the lung. J. Nanobiotechnology 19: 56. 
  19. Dai X, Zhao W, Tong X, Liu W, Zeng X, Duan X, et al. 2022. Non-clinical immunogenicity, biodistribution and toxicology evaluation of a chimpanzee adenovirus-based COVID-19 vaccine in rat and rhesus macaque. Arch. Toxicol. 96: 1437-1453. 
  20. Jeyanathan V, Afkhami S, D'Agostino MR, Zganiacz A, Feng X, Miller MS, et al. 2022. Differential biodistribution of adenoviral-vectored vaccine following intranasal and endotracheal deliveries leads to different immune outcomes. Front. Immunol. 13: 860399. 
  21. Condreay JP, Witherspoon SM, Clay WC, Kost TA. 1999. Transient and stable gene expression in mammalian cells transduced with a recombinant baculovirus vector. Proc. Natl. Acad. Sci. USA 96: 127-132. 
  22. Guidelines for assuring the quality and nonclinical safety evaluation of DNA vaccines. WHO Expert Committee on Biological Standardisation, (2005). Available at http://www.who.int/biologicals/publications/ECBS%202005%20Annex%201%20DNA.pdf. 
  23. Shin HY, Choi H, Kim N, Park N, Kim H, Kim J, et al. 2020. Unraveling the genome-wide impact of recombinant baculovirus infection in mammalian cells for gene delivery. Genes (Basel) 11: 1306. 
  24. Guidance for Industry: considerations for plasmid DNA vaccines for infectious disease indications. Available at http://www.fda.gov/cber/gdlns/plasdnavac.htm. 
  25. Cho HJ, Lee S, Im S, Kim MG, Lee J, Lee HJ, et al. 2012. Preclinical pharmacokinetics and biodistribution of human papillomavirus DNA vaccine delivered in human endogenous retrovirus envelope-coated baculovirus vector. Pharm. Res. 29: 585-593. 
  26. Liu C, Fan M, Xu Q, Li Y. 2008. Biodistribution and expression of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in mice. J. Gene Med. 10: 298-305. 
  27. Zhou QH, Wu C, Manickam DS, Oupicky D. 2009. Evaluation of pharmacokinetics of bioreducible gene delivery vectors by real-time PCR. Pharm. Res. 26: 1581-1589. 
  28. Fu J, Li D, Xia S, Song H, Dong Z, Chen F, et al. 2009. Absolute quantification of plasmid DNA by real-time PCR with genomic DNA as external standard and its application to a biodistribution study of an HIV DNA vaccine. Anal. Sci. 25: 675-680. 
  29. Raty JK, Liimatainen T, Huhtala T, Kaikkonen MU, Airenne KJ, Hakumaki JM, et al. 2007. SPECT/CT imaging of baculovirus biodistribution in rat. Gene Ther. 14: 930-938.