AAPS PharmSciTech

, Volume 13, Issue 2, pp 498–506 | Cite as

Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions

  • Christopher B. Fox
  • Susan L. Baldwin
  • Malcolm S. Duthie
  • Steven G. Reed
  • Thomas S. Vedvick
Research Article

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 

Supplementary material

12249_2012_9771_MOESM1_ESM.doc (384 kb)
ESM 1DOC 384 kb

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Copyright information

© American Association of Pharmaceutical Scientists 2012

Authors and Affiliations

  • Christopher B. Fox
    • 1
  • Susan L. Baldwin
    • 1
  • Malcolm S. Duthie
    • 1
    • 2
  • Steven G. Reed
    • 1
    • 3
  • Thomas S. Vedvick
    • 1
  1. 1.Infectious Disease Research InstituteSeattleUSA
  2. 2.Protein Advances Inc.SeattleUSA
  3. 3.Immune Design Corp.SeattleUSA

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