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What is the mode-of-action of water-in-oil adjuvant in inactivated viral vaccines?

Tuesday 21 November 2017

Robin van den Biggelaar

Vaccines form an essential component to prevent human or veterinary infectious diseases. Many of the vaccines have already been used for decades and have proven their safety and efficacy. However, the exact working mechanism of these vaccines at level of immune cells is often not known. To generate vaccines with a high safety profile, many vaccines are nowadays created by inactivation of bacterial or viral pathogens, in contrast to live attenuated vaccines. Unfortunately, the inactivation process comes at a cost, because it reduces immunestimulatory properties of the vaccine. To overcome this problem, inactivated vaccines can be supplemented with adjuvants, like aluminium salts and emulsifiers, which boost the immune response against the vaccine.

In this research project, our goal is to elucidate the mode-of-action of water-in-oil (w/o) adjuvants, which are commonly used in the veterinary field. More specifically, we study the innate immune response against an w/o adjuvant that is used for a large number of inactivated viral vaccines to vaccinate poultry, for example against Infectious Bronchitis Virus, Newcastle Disease Virus, Infectious bursal disease virus, and Avian Influenza Virus.

We will study the effects of the w/o adjuvant in at least two in vitro models: 1. a macrophage-like chicken cell line HD11 and 2. primary bone-marrow derived dendritic cell (BM-DC) cultures. After stimulation by the adjuvant, we will be able to evaluate its effect on phagocytosis, pro-inflammatory cytokine expression, chemokine expression, and cellular migration. These cellular assays will provide more knowledge about the working mechanism of adjuvants, but may also include potential platform technology for quality control of licensed vaccines that can substitute in vivo quality tests in animals.Techniques: Cell culture, flow cytometry, cell sorting (FACS), RNA isolation, real-time quantitative PCR, cellular migration assay.

6 - 9 months

R.H.G.A. van den Biggelaar, PhD student (R.H.G.A.vandenBiggelaar@uu.nl or 030 253 7448)

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• Seubert A, Monica E, Pizza M, O’Hagan DT, Wack A. The adjuvants aluminium hydroxide and MF59 induce monocyte and granulocyte chemoattractants and enhance monocyte differentiation toward dendritic cells. 2008. Journal of Immunology 180(8):5402-5412.
• O’Hagan DT, Ott GS, De Gregorio E, Seubert A. The mechanism of action of MF59 – An innately attractive adjuvant formulation. 2012. Vaccine 30(29):4341-4348.