Abstract
BackgroundSpecific cellular cytotoxic immune responses (CTL) are important in combating viral diseases and a highly desirable feature in the development of targeted HIV vaccines. Adjuvants are key components in vaccines and may assist the HIV immunogens in inducing the desired CTL responses. In search for appropriate adjuvants for CD8+ T cells it is important to measure the necessary immunological features e.g. functional cell killing/lysis in addition to immunological markers that can be monitored by simple immunological laboratory methods.Methodology/Principal FindingsWe tested the ability of a novel two component adjuvant, CAF01, consisting of the immune stimulating synthetic glycolipid TDB (Trehalose-Dibehenate) incorporated into cationic DDA (Dimethyldioctadecylammonium bromide) liposomes to induce CD8+ T-cell restricted cellular immune responses towards subdominant minimal HLA-A0201-restricted CTL epitopes from HIV-1 proteins in HLA-A*0201 transgenic HHD mice. CAF01 has an acceptable safety profile and is used in preclinical development of vaccines against HIV-1, malaria and tuberculosis.Conclusions/SignificanceWe found that CAF01 induced cellular immune responses against HIV-1 minimal CTL epitopes in HLA-A*0201 transgenic mice to levels comparable with that of incomplete Freund's adjuvant.
Highlights
Generation of cellular immune responses are of high significance in development of HIV-1 vaccines since the breath and expansion of cytotoxic T-lymphocytes (CTL) is associated with virus control [1,2,3]
Conclusions/Significance: We found that CAF01 induced cellular immune responses against HIV-1 minimal CTL epitopes in HLA-A*0201 transgenic mice to levels comparable with that of incomplete Freund’s adjuvant
The novel adjuvant CAF01 was compared with incomplete Freund’s adjuvants (IFA). We found that both the HLA-A2-restricted CD8 T-cell epitope Vif101 and the CD4 Th epitope PADRE induced high responses in IFN-c enzyme-linked immunospot (ELISPOT) in both the IFA and CAF01 groups (Figure 1A+B)
Summary
Generation of cellular immune responses are of high significance in development of HIV-1 vaccines since the breath and expansion of cytotoxic T-lymphocytes (CTL) is associated with virus control [1,2,3]. After selection of vaccine epitope peptides, it is important to find an appropriate adjuvant capable of inducing a strong cellular immune response. In this search it is important to look for the necessary immunological features e.g. cell killing/lysis and not just immunological markers that can be monitored by simple immunological laboratory methods. Specific cellular cytotoxic immune responses (CTL) are important in combating viral diseases and a highly desirable feature in the development of targeted HIV vaccines. In search for appropriate adjuvants for CD8+ T cells it is important to measure the necessary immunological features e.g. functional cell killing/lysis in addition to immunological markers that can be monitored by simple immunological laboratory methods
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