Microparticulate-encapsulated antigen with split topical CpG oligodeoxynucleotide adjuvant as a single-injection immunization strategy
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1
University of British Columbia, Dermatology & Skin Science, Canada
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2
University of British Columbia, Pharmaceutical Sciences, Canada
Antigen-presenting cells (APCs) are responsible for presenting foreign antigens to, and activating T cells to fight off infection. Manipulation of APCs to modulate immune responses to immunization has been a focus in vaccinology. Due to high frequencies of APCs in the skin, we are interested in the skin as a site for immunization. Keratinocytes and skin-resident plasmacytoid dendritic cells can be activated via binding of their Toll-like receptor 9 to CpG oligodeoxynucleotides (ODN) – synthetic DNA that mimic unmethylated CpG bacterial DNA. Here, we encapsulated the ovalbumin (OVA) antigen in polylactide co-glycolide microparticles (PLG-OVA) and show that mice immunized subcutaneously in a prime-boost regime with PLG-OVA generate antigen-specific cytotoxic T cells when CpG ODN is used as an adjuvant. Using flow cytometric analysis, 2.3% antigen-specific cells are detected within the CD8+ T cell population in the blood when CpG ODN is administered topically (P<0.05 compared to PLG-OVA alone). In addition, 0.8% of CD8+ splenocytes produce interferon-gamma when re-stimulated with OVA peptide (SIINFEKL) in vitro (P<0.001). The microparticles show a triphasic release of OVA which simulates two doses of antigen injected separately. Using this release property and a second topical application of adjuvant, we enhance the generation of antigen-specific cytotoxic T cells in the blood from 0.4 to 0.9% (P<0.05) and OVA-specific total IgG and IgG2c production, effectively generating a single-injection vaccine with split topical adjuvant administration that induces robust cytotoxic T cell and antibody responses. Generating single-injection vaccines may enhance vaccination compliance and may also decrease the cost of administration.
Keywords:
CpG oligodeoxynucleotide,
topical adjuvant,
microparticles,
CTL,
Vaccines
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
Lai
JC,
Esposito
TV,
Häfeli
UO and
Dutz
JP
(2013). Microparticulate-encapsulated antigen with split topical CpG oligodeoxynucleotide adjuvant as a single-injection immunization strategy.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00749
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Received:
13 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Jan P Dutz, University of British Columbia, Dermatology & Skin Science, Vancouver, British Columbia, V5Z 4H4, Canada, jan.dutz@ubc.ca