UCL SCHOOL OF PHARMACY
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Designer inorganic vaccine adjuvants
Dr Gareth Williams
g.williams@ucl.ac.uk; 0207 753 5868
5 November 2014
UCL SCHOOL OF PHARMACY
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Immunology 101
• Dendritic cells (DC) are key cells of immunity;
• Stationed around tissues of the body;
• DC sample local environments, and direct the appropriate
immune response.
Th1:
Destroy virally infected or
cancerous cells
Th2:
Destroy bacterial infections
and parasites
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Ensuring a potent vaccine
+
Vaccine =
Antigen

Adjuvant
“the development of new vaccine adjuvants for human use
has been one of the slowest processes in the history of
medicine. For almost a century, alum(s) have been the only
vaccine adjuvant approved worldwide” [Eur. J. Immunol.,
2008, 38, p2068].
UCL SCHOOL OF PHARMACY
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Ensuring a potent vaccine
+
Vaccine =
Antigen

Adjuvant
“the development of new vaccine adjuvants for human use
has been one of the slowest processes in the history of
medicine. For almost a century, alum(s) have been the only
vaccine adjuvant approved worldwide” [Eur. J. Immunol.,
2008, 38, p2068].
UCL SCHOOL OF PHARMACY
BRUNSWICK SQUARE
Ensuring a potent vaccine
+
Vaccine =
Antigen
Adjuvant
= (usually)
AlOOH
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The “dirty little secret”
• “A sterilized Al hydroxide solution”;
• 250 mL (1.3 % w/v) is about £50!
• MSDS formula: H3AlO3 = Al(OH)3.
Alhydrogel
AlOOH
Angle
(2θ)
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How do we solve a problem like alum?
Particle size and shape engineering
Make new family of adjuvants
• Entirely different materials –
liposomes, ISCOMs, virosomes…..
• Do minimum
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Bespoke disease-targeted inorganic vaccine adjuvants
+
Vaccine =
Antigen
Adjuvant
= (usually)
Just AlOOH.
Always. 
AlOOH
Which is closely related to:
Diverse
family of
materials. 
[M2M’(OH)6]X·yH2O
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Bespoke disease-targeted inorganic vaccine adjuvants
M,M’, OH
X, H2O
Make systematic substitutions
[M2M’(OH)6]X·yH2O
M: Li+, Mg2+, Ca2+
M’: Al3+, Fe3+
X: Cl-, NO3-, CO32-
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Experimental strategy
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Measuring maturity
Mature
Immature
Cytokines – made
inside cell then
released.
Co-stimulatory
molecules – grow
on surface of cell.
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In vitro data
• Dendritic cells exposed to various LDH adjuvants
J. Exp. Med. 2014, 211, 1019
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In vivo data
• Antibody levels in C57BL/6 mice
J. Exp. Med. 2014, 211, 1019
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In vivo data
• Killer T-cell induction
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Experimental strategy
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Systems vaccinology
J. Exp. Med. 2014, 211, 1019
UCL SCHOOL OF PHARMACY
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Conclusions
• LDHs are potent immunomodulators whose immunogenicity can be
predicted a priori from certain of their physicochemical properties;
• Because they have enormous chemical diversity they have significant
potential as bespoke adjuvants able to stimulate the required
immune response profile for a particular disease setting;
• Ultimately we will be able to screen 1000s of compounds in silico
permitting targeted synthesis of leads.
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Acknowledgments
• Oxford:
Prof Jon Austyn
Prof Dermot O’Hare
Dr Dan Lunn
Dr Stephen Preston
Oliwia Rysnik
• Ghent:
Prof Bart Lambrecht
Dr Mirjam Kool
Sofie De Prijck
Kaat Fierens