Adjuvanted influenza vaccines

Figures & data

Table 1. Licensed vaccines for influenza. Trivalent vaccines contain three strains, usually two influenza A (currently a representative H1N1 and H3N2 strain) and an influenza B strain (either a Yamagata lineage or Victoria lineage depending on what is currently circulating). Quadrivalent vaccines contain four strains two A and two B. Pandemic vaccines are pre-licensed in anticipation of that strain becoming more prevalent. Apart from Flublok which is recombinant protein, the majority of vaccines are egg derived and either whole virion, split (where the virus has been disrupted by a detergent) and subunit (where the haemagglutinin and neuraminidase proteins have been further purified, removing other viral proteins).

Product Name	Vaccine type	Manufacturer	Adjuvant	Currently in Use?	Age given
Influvac	Subunit, inactivated, Trivalent	Abbot Biologicals (Distributor Mylan)	None	Still in Use	≥6 months, higher doses for those over 3 years
Fluenz	live attenuated virus, Quadrivalent	AstraZeneca	None	Still in Use	≥24 months
Nasalfu	Subunit, inactivated Trivalent	Berna Biotech	Virosome Heat Labile enterotoxin (LT)	Not in use
Inflexal V	Subunit, inactivated Trivalent	Crucell (formerly Berna Biotech)	Virosome	Unclear	≥6 months, higher doses for those over 3 years
Panvax/ Panvax Junior	Split virion, inactivated Pandemic H1N1	CSL Ltd	None	Not in use	≥6 months
Fluvax/ Fluvax Junior	Split virion, inactivated Trivalent	CSL Ltd	Non	Still in use	≥5 years
Pandemrix	Split virion, inactivated, Pandemic H1N1	GSK	AS03	Not in use	≥6 months, higher doses for those over 10 years
Daronrix	Whole virion, inactivated, Pandemic H5N1	GSK	AlPO4 & Al(OH)3	Not in use	≥18 years
Prepandrix	Split virion, inactivated, Pandemic H5N1	GSK	AS03	Still in Use	≥18 years and double dose for >80 years
Arepanrix	Split virion, inactivated, Pandemic H1N1	GSK	AS03	Not in use	≥6 months
Fluarix	Split virion, inactivated, Quadrivalent	GSK	None	Still in use	≥3 years
Q-Pan H5N1	Split virion, inactivated, Pandemic H5N1	GSK	AS03	Still in use	≥6 months
Orniflu	Subunit, inactivated, Pandemic H5N1	Microgen Russia	Al(OH)3	Still in use	≥18 years
Imuvac	Subunit, inactivated, Trivalent	Mylan	None	Still in Use	≥6 months
Celtura	Subunit, inactivated, Pandemic H1N1	Novartis	MF59	Pandemic only	≥6 months
Focetria	Subunit, inactivated, Pandemic H1N1	Novartis	MF59C.1	Not in use	≥6 months
Fluval-AB/Fluval-P/Fluval-K	Whole virion, inactivated, Trivalent	Omnivest	AlPO4 gel	Still in Use	≥6 months
Enzira	Split virion, inactivated, Trivalent	Pfizer	None	Still in Use	≥5 years
Flublok	Recombinant protein, Trivalent	Protein Sciences	None	Still in Use	≥18 years
Emerflu	Split virion, inactivated, Pandemic H5N1	Sanofi Pasteur	AlPO4	Not in use	≥18 years when pandemic flu declared
Humenza	Split virion, inactivated, Pandemic H1N1	Sanofi Pasteur	AFO3	Not in use	≥6 months
Fluzone Quadrivalent	Split virion, inactivated, Quadrivalent	Sanofi Pasteur	None	Still in Use	≥3 years
Intanza	Split virion, inactivated, Trivalent	Sanofi Pasteur	None	Still in Use	≥60 years
Agrippal	Subunit, inactivated, Trivalent	Seqirus	None	Still in Use	≥6 months
Optaflu	Subunit, inactivated, Trivalent	Seqirus	None	Not in use	≥6 months
FluAd	Subunit, inactivated, Trivalent	Seqirus	MF59C.1	Still in Use	≥65 yrs
Panflu	Whole virion, inactivated, Pandemic H5N1	Sinovac	Al(OH)3	Still in Use	≥18 years

Table 2. Human clinical trials with experimental adjuvants (Pubmed influenza vaccine adjuvant: Clinicaltrials.gov condition influenza, other terms adjuvant).

Adjuvant Name	Adjuvant Class	Adjuvant Description	AssociatedCT.gov ref	Sponsor/ Associated	Study Date	Efficacy?	Related Paper
GLA	TLR	TLR4 ligand	NCT01147068.	IDRI	2012	GLA improved serum antibody response	^106
Imiquimod ointment	TLR	TLR7 agonist	NCT02103023	University of Hong Kong	2014	Increased antibody	^107
Aldara/Imiquimod	TLR	TLR7 topical agonist	NCT02960815	University of Lausanne	2016	None reported
Rintatolimod	TLR	TLR3 agonist (plus LAIV)	N/A	University Alabama/ Hemispherx	2014	No comparator	^108
Vax128	TLR	Haemagluttinin-flagellin fusion (TLR 5 agonist)	NCT01172054	Vaxinnate	2011	Reactogenic, no control for efficacy	^44
VAX102	TLR	Matrix protein-flagellin fusion	N/A	Vaxinnate	2011	Reactogenic	^110
CpG	TLR	TLR9 agonist	N/A	Coley Pharmaceutical Group	2004	No effect	^109
IC31	TLR	TLR9 agonist + uptake peptide	N/A	Intercell/ Novartis	2008	Data not published
ISS	TLR	TLR9 agonist	N/A	Dynavax	2011	Data not published
JVRS-100	Formulation	Cationic lipid/DNA complex	NCT00662272, NCT00936468	Colby Pharmaceutical	2008	None reported
MAS-1	Formulation	Nanoparticular, emulsion	NCT02500680 NCT01623232	Nova Immunotherapeutics/ Mercia	2015	None reported
Vaxisome	Formulation	Cholesterol liposome	NCT00915187	NasVax	2009	None reported
PAL	Formulation	Papaya mosaic virus nanoparticle	NCT02188810	Folia Biotech	2014	None reported
Matrix-M1	Formulation	Saponin, cholesterol and phospholipid (ISCOM)	NCT01897701 NCT01444482	Novavax	2013	Increased antibody	^142
Montantide	Formulation	Water in oil	NCT00877448	BiondVax Ltd	2009	Adjuvant increased response	^143
Proteosome	Formulation	Bacterial hydrophobic outer membrane proteins	NCT02522754	hVIVO	2015	No comparator	^144
W805EC	Formulation	Nanoemulsion delivered intranasally with Fluzone	N/A	NanoBio Corporation	2012	No difference with antigen alone	^145
ISCOM	Formulation	Immune stimulating complexes	N/A	Erasmus	2000	More rapid antibody response	^146
Liposome	Formulation	Oligolamellar phospholipid	N/A	St Louis University	1995	Improved CD8 response	^147
NanoStat, NB1008	Formulation	Emulsion	NCT01333462/NCT01354379	NanoBio	2011	No results reported
Type IInterferon	Cytokine	Cytokine delivered mucosally	NCT00436046	Baylor College	2007	No effect	^113
IL-2	Cytokine	Cytokine	N/A	Hebrew University, Jerusalem	2003	Boosted antibody responses	^111
GM-CSF	Cytokine	Cytokine	N/A	Emory University	2002	No effect	^112
LT Patch	Immunostimulator	Heat labile enterotoxin	NCT00908687	Intercell	2009	Boosted primary response	^148
BCG	Immunostimulator	Nonspecific immunity, delivered 14 days before vaccine	N/A	Radboud Institute for Health Sciences	2015	Increased response	^149
Advax	Immunostimulator	Polysaccharide/ delta Inulin	ACTRN1261200 0709842	Vaxine	2015	Increase in B cell response	^150^,^151
OM-85 BV	Immunostimulator	Mixed Bacterial lysate	N/A	Fondazione IRCCS	2014	No effect	^152
OMP-TIV	Formulation/ Immunostimulator	Meningococcal outer membrane proteins	N/A	GSK	2011	No antigen alone control	^153
Mimopath/ FluGEM	Formulation/ Immunostimulator	Bacterium Like Particles	N/A	Mucosis	2012	None reported
Nasalflu/ LT	Formulation/Immunostimulator	Virosomal-Subunit adjuvanted LT	N/A	Berna Biotech	2000	Effective but 46 cases Bell's Palsey	^98
sLAG-3(IMP321)	Immunostimulator	MHC II ligand	N/A	Immutep	2006	No effect on antibody, increased T cell response	^154
QS21	Immunostimulator	Saponin	N/A	Baylor	2006	No effect	^155
DHEAS	Immunostimulator	Dehydroepiandrosterone sulphate	N/A	Paradigm Biosciences	1997	No effect	^156^,^157

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