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Screening Vaccine Formulations in Fresh Human Whole Blood

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Vaccine Adjuvants

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1494))

Abstract

Monitoring the immunological functionality of vaccine formulations is critical for vaccine development. While the traditional approach using established animal models has been relatively effective, the use of animals is costly and cumbersome, and animal models are not always reflective of a human response. The development of a human-based approach would be a major step forward in understanding how vaccine formulations might behave in humans. Here, we describe a platform methodology using fresh human whole blood (hWB) to monitor adjuvant-modulated, antigen-specific responses to vaccine formulations, which is amenable to analysis by standard immunoassays as well as a variety of other analytical techniques.

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References

  1. Rice J (2012) Animal models: not close enough. Nature 484:S9

    Article  PubMed  Google Scholar 

  2. Cook N, Jodrell DI, Tuveson DA (2012) Predictive in vivo animal models and translation to clinical trials. Drug Discov Today 17:253–260

    Article  PubMed  Google Scholar 

  3. Greek R, Menache A, Rice MJ (2012) Animal models in an age of personalized medicine. Personal Med 9:47–64

    Article  Google Scholar 

  4. Davis MM (2008) A prescription for human immunology. Immunity 29:835–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Duthie MS, Windish HP, Fox CB, Reed SG (2011) Use of defined TLR ligands as adjuvants within human vaccines. Immunol Rev 239:178–196

    Article  CAS  PubMed  Google Scholar 

  6. Higbee RG, Byers AM, Dhir V, Drake D, Fahlenkamp HG, Gangur J, Kachurin A, Kachurina O, Leistritz D, Ma Y, Mehta R, Mishkin E, Moser J, Mosquera L, Nguyen M, Parkhill R, Pawar S, Poisson L, Sanchez-Schmitz G, Schanen B, Singh I, Song H, Tapia T, Warren W, Wittman V (2009) An immunologic model for rapid vaccine assessment – a clinical trial in a test tube. Altern Lab Anim 37:19–27

    CAS  PubMed  Google Scholar 

  7. Brookes RH, Hakimi J, Ha Y, Aboutorabian S, Ausar SF, Hasija M, Smith SG, Todryk SM, Dockrell HM, Rahman N (2014) Screening vaccine formulations for biological activity using fresh human whole blood. Hum Vaccin Immunother 10(4):1129–1135

    Article  PubMed  PubMed Central  Google Scholar 

  8. Aboutorabian S, Hakimi J, Boudet F, Montano S, Dookie A, Roque C, Ausar SF, Rahman N, Brookes RH (2015) A high ratio of IC31 adjuvant to antigen is necessary for H4 TB vaccine immunomodulation. Hum Vaccin Immunother 11(6):1449–1455

    Article  PubMed  PubMed Central  Google Scholar 

  9. Damsgaard CT, Lauritzen L, Calder PC, Kjaer TM, Frokiaer H (2009) Whole-blood culture is a valid low-cost method to measure monocytic cytokines – a comparison of cytokine production in cultures of human whole-blood, mononuclear cells and monocytes. J Immunol Methods 340:95–101

    Article  CAS  PubMed  Google Scholar 

  10. Weir RE, Morgan AR, Britton WJ, Butlin CR, Dockrell HM (1994) Development of a whole blood assay to measure T cell responses to leprosy: a new tool for immune-epidemiological field studies of leprosy immunity. J Immunol Methods 176:93–101

    Article  CAS  PubMed  Google Scholar 

  11. Silva D, Ponte CGG, Hacker MA, Antas PRZ (2013) A whole blood assay as a simple, broad assessment of cytokines and chemokines to evaluate human immune responses to Mycobacterium tuberculosis antigens. Acta Trop 127:75–81

    Article  CAS  PubMed  Google Scholar 

  12. Chen J, Bruns AH, Donnelly HK, Wunderink RG (2010) Comparative in vitro stimulation with lipopolysaccharide to study TNFalpha gene expression in fresh whole blood, fresh and frozen peripheral blood mononuclear cells. J Immunol Methods 257:33–37

    Article  Google Scholar 

  13. Fox CB, Sivananthan SJ, Duthie MS, Vergara J, Guderian JA, Moon E, Coblentz D, Reed SG, Carter D (2014) A nanoliposome delivery system to synergistically trigger TLR4 and TLR7. J Nanobiotechnol 12:17

    Article  Google Scholar 

  14. Nauseef WM, Borregaard N (2014) Neutrophils at work. Nat Immunol 15(7):602–611

    Article  CAS  PubMed  Google Scholar 

  15. Davey MS, Morgan MP, Liuzzi AR, Tyler CJ, Khan MWA, Szakmany T, Hall JE, Moser B, Eberl M (2014) Microbe-specific unconventional T cells induce human neutrophil differentiation into antigen cross-presenting cells. J Immunol 193(7):3704–3716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mantovani A, Cassatella MA, Costantini C, Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531

    Article  CAS  PubMed  Google Scholar 

  17. O'Hagan DT, Fox CB (2015) Are we entering a new age for human vaccine adjuvants? Expert Rev Vaccines 14:909–911

    Article  PubMed  Google Scholar 

  18. Reed SG, Orr MT, Fox CB (2013) Key roles of adjuvants in modern vaccines. Nat Med 19:1597–1608

    Article  CAS  PubMed  Google Scholar 

  19. Centers for Disease Control and Prevention (2012). Guidelines for safe work practices in human and animal medical diagnostic laboratories. http://www.cdc.gov/mmwr/pdf/other/su6101.pdf. Accessed 11 Nov 2015

  20. Coch C, Luck C, Schwickart A, Putschli B, Renn M, Holler T, Barchet W, Hartmann G, Schlee M (2013) A human in vitro whole blood assay to predict the systemic cytokine response to therapeutic oligonucleotides including siRNA. PLoS One 8:e71057

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bandura DR, Baranov VI, Ornatsky OI, Antonov A, Kinach R, Lou X, Pavlov S, Vorobiev S, Dick JE, Tanner SD (2009) Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry. Anal Chem 81:6813–6822

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Roger H. Brookes .

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Hakimi, J., Aboutorabian, S., To, F., Ausar, S.F., Rahman, N., Brookes, R.H. (2017). Screening Vaccine Formulations in Fresh Human Whole Blood. In: Fox, C. (eds) Vaccine Adjuvants. Methods in Molecular Biology, vol 1494. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6445-1_22

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  • DOI: https://doi.org/10.1007/978-1-4939-6445-1_22

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6443-7

  • Online ISBN: 978-1-4939-6445-1

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