AAPS PharmSciTech

, Volume 13, Issue 2, pp 498–506

Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions

Authors

    • Infectious Disease Research Institute
  • Susan L. Baldwin
    • Infectious Disease Research Institute
  • Malcolm S. Duthie
    • Infectious Disease Research Institute
    • Protein Advances Inc.
  • Steven G. Reed
    • Infectious Disease Research Institute
    • Immune Design Corp.
  • Thomas S. Vedvick
    • Infectious Disease Research Institute
Research Article

DOI: 10.1208/s12249-012-9771-x

Cite this article as:
Fox, C.B., Baldwin, S.L., Duthie, M.S. et al. AAPS PharmSciTech (2012) 13: 498. doi:10.1208/s12249-012-9771-x

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 emulsionphosphatidylcholinesqualenevaccine adjuvant

Supplementary material

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

Copyright information

© American Association of Pharmaceutical Scientists 2012