Vaccine adjuvant activity of emulsified oils from species of the Pinaceae family.
BACKGROUND
Next to aluminum salts, squalene nanoemulsions comprise the most widely employed class of adjuvants in approved vaccines. Despite their importance, the mechanisms of action of squalene nanoemulsions are not completely understood, nor are the structure/function requirements of the oil composition.


PURPOSE
In this study, we build on previous work that compared the adjuvant properties of nanoemulsions made with different classes of oil structures to squalene nanoemulsion. Here, we introduce nanoemulsions made with polyprenols derived from species of the Pinaceae family as novel vaccine adjuvant compositions. In contrast with long-chain triglycerides that do not efficiently enhance an immune response, both polyprenols and squalene are comprised of multimeric isoprene units, which may represent an important structural property of oils in nanoemulsions with adjuvant properties.


STUDY DESIGN
Oils derived from species of the Pinaceae family were formulated in nanoemulsions, with or without a synthetic Toll-like receptor 4 (TLR4) ligand, and characterized regarding physicochemical and biological activity properties in comparison to squalene nanoemulsions.


METHODS
Oils were extracted from species of the Pinaceae family and used to prepare oil-in-water nanoemulsions by microfluidization. Emulsion droplet diameter stability was characterized by dynamic light scattering. Nanoemulsions were evaluated for in vitro biological activity using human whole blood, and in vivo biological activity in mouse, pig, and ferret models when combined with pandemic influenza vaccine antigens.


RESULTS
Nanoemulsions comprised of Pinaceae-derived polyprenol oils demonstrated long-term physical stability, stimulated cytokine production from human cells in vitro, and promoted antigen-specific immune responses in various animal models, particularly when formulated with the TLR4 ligand glucopyranosyl lipid adjuvant (GLA).


CONCLUSION
Pinaceae-derived nanoemulsions are compatible with inclusion of a synthetic TLR4 ligand and promote antigen-specific immune responses to pandemic influenza antigens in mouse, pig, and ferret models.
['Fox|Christopher B|CB|', 'Van Hoeven|Neal|N|', 'Granger|Brian|B|', 'Lin|Susan|S|', 'Guderian|Jeffrey A|JA|', 'Hartwig|Airn|A|', 'Marlenee|Nicole|N|', 'Bowen|Richard A|RA|', 'Soultanov|Vagif|V|', 'Carter|Darrick|D|']
D000276:Adjuvants, Immunologic D000818:Animals D004655:Emulsions D005260:Female D005289:Ferrets D006801:Humans D007252:Influenza Vaccines D007251:Influenza, Human D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D028201:Pinaceae D010938:Plant Oils D000081026:Polyprenols D013047:Specific Pathogen-Free Organisms D013185:Squalene D013552:Swine D051197:Toll-Like Receptor 4
Vaccine adjuvant Squalene Nanoemulsion Polyprenols Influenza Conifers