Research Article

AAPS PharmSciTech

, Volume 13, Issue 2, pp 498-506

First online:

Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions

  • Christopher B. FoxAffiliated withInfectious Disease Research Institute Email author 
  • , Susan L. BaldwinAffiliated withInfectious Disease Research Institute
  • , Malcolm S. DuthieAffiliated withInfectious Disease Research InstituteProtein Advances Inc.
  • , Steven G. ReedAffiliated withInfectious Disease Research InstituteImmune Design Corp.
  • , Thomas S. VedvickAffiliated withInfectious Disease Research Institute

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Abstract

Egg phosphatidylcholine is commonly used as an emulsifier in formulations administered parenterally. However, synthetic phosphatidylcholine (PC) emulsifiers are now widely available and may be desirable substitutes for egg-derived phospholipids due to stability, purity, and material source considerations. In earlier work, we demonstrated that a squalene–1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) emulsion provided equivalent physical stability compared to a squalene–egg PC emulsion. In the present manuscript, we evaluate the physical stability of vaccine adjuvant emulsions containing a range of other synthetic phosphatidylcholine emulsifiers. Besides the POPC emulsion, the 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) emulsion showed good particle size and visual stability compared to emulsions made with other synthetic phospholipids. Moreover, comparable immune responses were elicited by squalene emulsions employing various synthetic PC or egg PC emulsifiers in combination with an inactivated influenza vaccine or a recombinant malaria antigen, and these responses were generally enhanced compared to antigen without adjuvant. Therefore, we show that (1) some synthetic PCs (DMPC, POPC, and to a lesser extent 1,2-dioleoyl-sn-glycero-3-phosphocholine) are effective stabilizers of squalene emulsion over a range of storage temperatures while others are not (1,2-distearoyl-sn-glycero-3-phosphocholine, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, and 1,2-dilauroyl-sn-glycero-3-phosphocholine) and (2) the immunogenicity of stable squalene emulsions is similar regardless of PC source.

Key words

oil-in-water emulsion phosphatidylcholine squalene vaccine adjuvant