Multi-compartmental vaccine delivery system for enhanced immune response to gp100 peptide antigen in melanoma immunotherapy.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 110 Mugar Life Sciences Building, Boston, Massachusetts 02115, USA.
Mayurkumar
M
Kalariya
Srinivas
S
Ganta
Mansoor
M
Amiji
D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood / Q000276:immunology; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D007114:Immunization; D008546:Melanoma, Experimental / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D009821:Oils / Q000737:chemistry; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D058951:gp100 Melanoma Antigen / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use*
D019496:Cancer Vaccines; D016207:Cytokines; D004655:Emulsions; D009821:Oils; D058951:gp100 Melanoma Antigen