Lipid Nanoparticle Formulation Increases Efficiency of DNA-Vectored Vaccines/Immunoprophylaxis in Animals Including Transchromosomic Bovines.
Animals
Animals, Genetically Modified
Antibodies, Monoclonal
/ immunology
Antibodies, Neutralizing
/ immunology
Antibodies, Viral
/ immunology
Cattle
Chlorocebus aethiops
Chromosomes, Artificial, Human
/ genetics
Dose-Response Relationship, Immunologic
Female
Genes, Immunoglobulin
Orthohantavirus
/ immunology
Macaca fascicularis
Male
Nanoparticles
/ administration & dosage
Neutralization Tests
Plasmids
Poxviridae
/ immunology
Rabbits
Vaccines, DNA
Vero Cells
Viral Vaccines
/ immunology
Zika Virus
/ immunology
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 05 2020
29 05 2020
Historique:
received:
11
11
2019
accepted:
16
04
2020
entrez:
31
5
2020
pubmed:
31
5
2020
medline:
15
12
2020
Statut:
epublish
Résumé
The use of nucleic acid as a drug substance for vaccines and other gene-based medicines continues to evolve. Here, we have used a technology originally developed for mRNA in vivo delivery to enhance the immunogenicity of DNA vaccines. We demonstrate that neutralizing antibodies produced in rabbits and nonhuman primates injected with lipid nanoparticle (LNP)-formulated Andes virus or Zika virus DNA vaccines are elevated over unformulated vaccine. Using a plasmid encoding an anti-poxvirus monoclonal antibody (as a reporter of protein expression), we showed that improved immunogenicity is likely due to increased in vivo DNA delivery, resulting in more target protein. Specifically, after four days, up to 30 ng/mL of functional monoclonal antibody were detected in the serum of rabbits injected with the LNP-formulated DNA. We pragmatically applied the technology to the production of human neutralizing antibodies in a transchromosomic (Tc) bovine for use as a passive immunoprophylactic. Production of neutralizing antibody was increased by >10-fold while utilizing 10 times less DNA in the Tc bovine. This work provides a proof-of-concept that LNP formulation of DNA vaccines can be used to produce more potent active vaccines, passive countermeasures (e.g., Tc bovine), and as a means to produce more potent DNA-launched immunotherapies.
Identifiants
pubmed: 32472093
doi: 10.1038/s41598-020-65059-0
pii: 10.1038/s41598-020-65059-0
pmc: PMC7260227
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Antibodies, Viral
0
Vaccines, DNA
0
Viral Vaccines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8764Références
Brocato, R.L. & Hooper, J.W. Progress on the Prevention and Treatment of Hantavirus Disease. Viruses 11(2019).
Musso, D. & Gubler, D. J. Zika Virus. Clin. Microbiol. Rev. 29, 487–524 (2016).
doi: 10.1128/CMR.00072-15
Wang, A., Thurmond, S., Islas, L., Hui, K. & Hai, R. Zika virus genome biology and molecular pathogenesis. Emerg. Microbes Infect. 6, e13 (2017).
pubmed: 28325921
pmcid: 5378920
Fernandez, E. & Diamond, M. S. Vaccination strategies against Zika virus. Curr. Opin. virology 23, 59–67 (2017).
doi: 10.1016/j.coviro.2017.03.006
Musso, D., Baud, D. & Gubler, D. J. Zika virus: what do we know? Clin. microbiology infection: Off. Publ. Eur. Soc. Clin. Microbiology Infect. Dis. 22, 494–496 (2016).
doi: 10.1016/j.cmi.2016.03.032
Kwilas, S. et al. A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring-powered jet injector elicits a potent neutralizing antibody response in rabbits and nonhuman primates. Curr. gene Ther. 14, 200–210 (2014).
doi: 10.2174/1566523214666140522122633
Hooper, J. W., Custer, D. M., Smith, J. & Wahl-Jensen, V. Hantaan/Andes virus DNA vaccine elicits a broadly cross-reactive neutralizing antibody response in nonhuman primates. Virology 347, 208–216 (2006).
doi: 10.1016/j.virol.2005.11.035
Custer, D. M., Thompson, E., Schmaljohn, C. S., Ksiazek, T. G. & Hooper, J. W. Active and passive vaccination against hantavirus pulmonary syndrome with Andes virus M genome segment-based DNA vaccine. J. virology 77, 9894–9905 (2003).
doi: 10.1128/JVI.77.18.9894-9905.2003
Muthumani, K. et al. In vivo protection against ZIKV infection and pathogenesis through passive antibody transfer and active immunisation with a prMEnv DNA vaccine. NPJ vaccines 1, 16021 (2016).
doi: 10.1038/npjvaccines.2016.21
Abbink, P. et al. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys. Science 353, 1129–1132 (2016).
doi: 10.1126/science.aah6157
Larocca, R. A. et al. Vaccine protection against Zika virus from Brazil. Nature 536, 474–478 (2016).
doi: 10.1038/nature18952
Dowd, K. A. et al. Rapid development of a DNA vaccine for Zika virus. Science 354, 237–240 (2016).
doi: 10.1126/science.aai9137
Garg, H., Mehmetoglu-Gurbuz, T. & Joshi, A. Recent Advances in Zika Virus Vaccines. Viruses 10(2018).
Barrett, A. D. T. Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation. NPJ vaccines 3, 24 (2018).
doi: 10.1038/s41541-018-0061-9
Stein, D. R. et al. Human polyclonal antibodies produced in transchromosomal cattle prevent lethal Zika virus infection and testicular atrophy in mice. Antivir. Res. 146, 164–173 (2017).
doi: 10.1016/j.antiviral.2017.09.005
Hooper, J. W. et al. DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome. Sci. Transl. Med. 6, 264ra162 (2014).
doi: 10.1126/scitranslmed.3010082
Lee, J., Arun Kumar, S., Jhan, Y. Y. & Bishop, C. J. Engineering DNA vaccines against infectious diseases. Acta Biomater. 80, 31–47 (2018).
doi: 10.1016/j.actbio.2018.08.033
Ramaswamy, S. et al. Systemic delivery of factor IX messenger RNA for protein replacement therapy. Proc. Natl Acad. Sci. U S Am. 114, E1941–E1950 (2017).
doi: 10.1073/pnas.1619653114
Yaghi, N. K. et al. Immune modulatory nanoparticle therapeutics for intracerebral glioma. Neuro Oncol. 19, 372–382 (2017).
pubmed: 27765835
Strickland, J. et al. Status of acute systemic toxicity testing requirements and data uses by U.S. regulatory agencies. Regul. Toxicol. Pharmacol. 94, 183–196 (2018).
doi: 10.1016/j.yrtph.2018.01.022
Hooper, J. W. et al. A Phase 1 clinical trial of Hantaan virus and Puumala virus M-segment DNA vaccines for haemorrhagic fever with renal syndrome delivered by intramuscular electroporation. Clin. microbiology infection: Off. Publ. Eur. Soc. Clin. Microbiology Infect. Dis. 20 Suppl 5, 110–117 (2014).
doi: 10.1111/1469-0691.12553
Mucker, E. M. et al. Intranasal monkeypox marmoset model: Prophylactic antibody treatment provides benefit against severe monkeypox virus disease. PLoS neglected tropical Dis. 12, e0006581 (2018).
doi: 10.1371/journal.pntd.0006581
Patel, A. et al. In Vivo Delivery of Synthetic Human DNA-Encoded Monoclonal Antibodies Protect against Ebolavirus Infection in a Mouse Model. Cell Rep. 25, 1982–1993 e1984 (2018).
doi: 10.1016/j.celrep.2018.10.062
Muthumani, K. et al. Rapid and Long-Term Immunity Elicited by DNA-Encoded Antibody Prophylaxis and DNA Vaccination Against Chikungunya Virus. The. J. Infect. Dis. 214, 369–378 (2016).
doi: 10.1093/infdis/jiw111
Elliott, S. T. C. et al. DMAb inoculation of synthetic cross reactive antibodies protects against lethal influenza A and B infections. NPJ vaccines 2, 18 (2017).
doi: 10.1038/s41541-017-0020-x
Tjelle, T. E. et al. Monoclonal antibodies produced by muscle after plasmid injection and electroporation. Mol. therapy: J. Am. Soc. Gene Ther. 9, 328–336 (2004).
doi: 10.1016/j.ymthe.2003.12.007
Tousignant, J. D. et al. Comprehensive analysis of the acute toxicities induced by systemic administration of cationic lipid:plasmid DNA complexes in mice. Hum. Gene Ther. 11, 2493–2513 (2000).
doi: 10.1089/10430340050207984
Lv, H., Zhang, S., Wang, B., Cui, S. & Yan, J. Toxicity of cationic lipids and cationic polymers in gene delivery. J. controlled release: Off. J. Controlled Rel. Soc. 114, 100–109 (2006).
doi: 10.1016/j.jconrel.2006.04.014
Zhang, J. S., Liu, F. & Huang, L. Implications of pharmacokinetic behavior of lipoplex for its inflammatory toxicity. Adv. drug. delivery Rev. 57, 689–698 (2005).
doi: 10.1016/j.addr.2004.12.004
Neyns, B. et al. Contaminants within bacterial plasmid preparations trigger apoptosis in liposome transfected OVCAR3, but not in SKOV3 or AZ224 human ovarian cancer cells. Cell Biol. Int. 25, 715–723 (2001).
doi: 10.1006/cbir.2001.0767
Bazzani, R. P., Cai, Y., Hebel, H. L., Hyde, S. C. & Gill, D. R. The significance of plasmid DNA preparations contaminated with bacterial genomic DNA on inflammatory responses following delivery of lipoplexes to the murine lung. Biomaterials 32, 9854–9865 (2011).
doi: 10.1016/j.biomaterials.2011.08.092
Hooper, J. W., Larsen, T., Custer, D. M. & Schmaljohn, C. S. A lethal disease model for hantavirus pulmonary syndrome. Virology 289, 6–14 (2001).
doi: 10.1006/viro.2001.1133
Golden, J. W., Maes, P., Kwilas, S. A., Ballantyne, J. & Hooper, J. W. Glycoprotein-Specific Antibodies Produced by DNA Vaccination Protect Guinea Pigs from Lethal Argentine and Venezuelan Hemorrhagic Fever. J. virology 90, 3515–3529 (2016).
doi: 10.1128/JVI.02969-15
Sano, A. et al. Physiological level production of antigen-specific human immunoglobulin in cloned transchromosomic cattle. PLoS one 8, e78119 (2013).
doi: 10.1371/journal.pone.0078119
Kuroiwa, Y. et al. Antigen-specific human polyclonal antibodies from hyperimmunized cattle. Nat. Biotechnol. 27, 173–181 (2009).
doi: 10.1038/nbt.1521
Matsushita, H. et al. Species-Specific Chromosome Engineering Greatly Improves Fully Human Polyclonal Antibody Production Profile in Cattle. PLoS one 10, e0130699 (2015).
doi: 10.1371/journal.pone.0130699