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Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions

AAPS PharmSciTech volume 13, pages 498–506 (2012)Cite this 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.

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Acknowledgments

The authors wish to thank Susan Lin, Sandra Sivananthan, Tim Dutill, Kristen Forseth, Tony Phan, Farah Mompoint, Tara Evers, Alison Bernard, and Marah Hay for skilled technical assistance and Dr. Martin Friede for helpful discussions. This work was supported in part by National Institutes of Health contract HHSN272200800045C and grant 42387 from the Bill and Melinda Gates Foundation. The authors gratefully acknowledge Dr. Evelina Angov for kindly providing the codon-harmonized PbCSP construct developed by Walter Reed Army Institute of Research.

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Authors and Affiliations

  1. Infectious Disease Research Institute, 1124 Columbia St, Ste 400, Seattle, Washington, 98104, USA

    Christopher B. Fox, Susan L. Baldwin, Malcolm S. Duthie, Steven G. Reed & Thomas S. Vedvick

  2. Protein Advances Inc., 1102 Columbia St, Ste 110, Seattle, Washington, 98104, USA

    Malcolm S. Duthie

  3. Immune Design Corp., 1124 Columbia St, Ste 700, Seattle, Washington, 98104, USA

    Steven G. Reed

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  1. Christopher B. Fox
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  2. Susan L. Baldwin
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  3. Malcolm S. Duthie
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  4. Steven G. Reed
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  5. Thomas S. Vedvick
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Correspondence to Christopher B. Fox.

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Fox, C.B., Baldwin, S.L., Duthie, M.S. et al. Immunomodulatory and Physical Effects of Phospholipid Composition in Vaccine Adjuvant Emulsions. AAPS PharmSciTech 13, 498–506 (2012). https://doi.org/10.1208/s12249-012-9771-x

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  • DOI: https://doi.org/10.1208/s12249-012-9771-x

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