. Author manuscript; available in PMC: 2012 Jun 1.

Published in final edited form as: Nat Immunol. 2011 Jun;12(6):509–517. doi: 10.1038/ni.2039

Table 2.

Innate immune activation by vaccines and adjuvants

	Innate immune mechanism	Type of immune response
Licensed vaccine
Yellow fever (YF-17D)	Activates multiple DC subsets through TLR2, TLR3, TLR7, TLR8 and TLR9; activates RIG-I and Mda5	CTLs; T_H1 and T_H2; neutralizing antibody
Smallpox (vaccinia virus)	Inhibits DC activation and causes cell death; blocks TLR4 and TLR3 signaling	CTLs; neutralizing antibody
Bacillus Calmette-Guérin	Activates TLR2, TLR4, TLR9 and DC-SIGN	T_H1 and T_H2
Licensed adjuvant- vaccine combinations
Alum	TLR signaling not critical for induction of antibody responses; induces caspase-1 and inflammasome activation in DCs	T_H2; antibody
MF59	Mechanism unknown; enhanced uptake by antigen presenting cells probably important	T_H2; antibody
AS04	TLR4 agonist	T_H1; antibody
Emerging adjuvants
CpG DNA	TLR9 ligand	T_H1, antibody
TLR7 and TLR8 ligands	TLR7 ligands	T_H1, antibody
Flagellin-protein fusions	Activates TLR5 and the inflammasome components IPAF and NAIP5	T_H1 and T_H2

Innate immune activation by some licensed vaccines and vaccine-adjuvant combinations, and emerging adjuvants being used in combination with various vaccines (these have been shown to stimulate innate immunity in clinical trials in combination with a variety of vaccines). MF59 is licensed in Europe in combination with the Novartis vaccine against influenza; AS04, an MPL derivative, is licensed for use in Europe in combination with vaccine against hepatitis B.