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Multi-Compartmental Vaccine Delivery System for Enhanced Immune Response to gp100 Peptide Antigen in Melanoma Immunotherapy

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Abstract

Purpose

To develop a multi-compartmental vaccine delivery system for safe and efficient delivery of the gp100 peptide antigen in melanoma immunotherapy.

Methods

Water-in-oil-in-water (W/O/W) multiple emulsion-based multi-compartmental vaccine delivery system containing the gp100 peptide was prepared by a two-step emulsification method. In vivo prophylactic and active immunization effectiveness of the novel squalane oil-containing gp100 vaccine was evaluated in the murine B16 melanoma model and compared with that of an incomplete Freund’s adjuvant (IFA)-based vaccine.

Results

Morphological evaluation of the W/O/W multiple emulsions showed that the oil-droplets were homogenously dispersed with the gp100 peptide encapsulated in an inner aqueous phase. Immunization with the gp100 peptide delivered in the W/O/W multiple emulsions-based vaccine resulted in increased protection against tumor challenge compared to IFA-based vaccine (p < 0.05, n = 8) signifying induction of enhanced anti-tumor immunity. In addition, serum Th1 cytokine levels and immuno-histochemistry of excised tumor tissues indicated activation and local infiltration of antigen specific cytotoxic T-lymphocytes into and/or surrounding the tumor mass. Moreover, the newly developed vaccine formulation did not induce any overt systemic toxicity.

Conclusion

Novel W/O/W multiple emulsions-based vaccine efficiently delivers the gp100 peptide antigen to induce cell-mediated anti-tumor immunity and offers an alternate, safe vaccine delivery system.

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Abbreviations

APCs:

antigen-presenting cells

CTLs:

cytotoxic T-lymphocytes

IFA:

incomplete Freund’s adjuvant

PBS:

phosphate-buffered saline

SME:

squalane oil multiple emulsions

W/O/W:

water-in-oil-in-water

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Acknowledgments AND DISCLOSURES

The authors wish to thank Husain Attarwala, Milind Chalishazar, and Lavanya Thapa for their help with some of the experimental procedures.

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, Massachusetts, 02115, USA

    Mayurkumar Kalariya & Mansoor Amiji

  2. Nemucore Medical Innovations, Inc., 55 Union Street, Worcester, Massachusetts, 01608, USA

    Srinivas Ganta

Authors
  1. Mayurkumar Kalariya
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  2. Srinivas Ganta
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  3. Mansoor Amiji
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Correspondence to Mansoor Amiji.

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Kalariya, M., Ganta, S. & Amiji, M. Multi-Compartmental Vaccine Delivery System for Enhanced Immune Response to gp100 Peptide Antigen in Melanoma Immunotherapy. Pharm Res 29, 3393–3403 (2012). https://doi.org/10.1007/s11095-012-0834-1

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  • DOI: https://doi.org/10.1007/s11095-012-0834-1

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