Background Specific 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 Findings We 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/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.
Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, et al. (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68: 4650–4655.
Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, et al. (1999) Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 189: 991–998.
Vangala A, Kirby D, Rosenkrands I, Agger EM, Andersen P, et al. (2006) A comparative study of cationic liposome and niosome-based adjuvant systems for protein subunit vaccines: characterisation, environmental scanning electron microscopy and immunisation studies in mice. J Pharm Pharmacol 58: 787–799.
Davidsen J, Rosenkrands I, Christensen D, Vangala A, Kirby D, et al. (2005) Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6′-dibehenate)-a novel adjuvant inducing both strong CMI and antibody responses. Biochim Biophys Acta 1718: 22–31.
Thorn M, Tang S, Therrien D, Kloverpris H, Vinner L, et al. (2007) Sequence conservation of subdominant HLA-A2-binding CTL epitopes in HIV-1 clinical isolates and CD8+ T-lymphocyte cross-recognition may explain the immune reaction in infected individuals. APMIS 115: 757–768.
Kloverpris HN, Karlsson I, Bonde J, Thorn M, Vinner L, et al. (2009) Induction of Novel CD8+ T Cell Responses During Chronic Untreated HIV-1 Infection by Immunization with Subdominant CTL Epitopes. AIDS 23: 1329–1340.
Pascolo S, Bervas N, Ure JM, Smith AG, Lemonnier FA, et al. (1997) HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. J Exp Med 185: 2043–2051.
Alexander J, Sidney J, Southwood S, Ruppert J, Oseroff C, et al. (1994) Development of high potency universal DR-restricted helper epitopes by modification of high affinity DR-blocking peptides. Immunity 1: 751–761.
Wilson CC, Palmer B, Southwood S, Sidney J, Higashimoto Y, et al. (2001) Identification and antigenicity of broadly cross-reactive and conserved human immunodeficiency virus type 1-derived helper T-lymphocyte epitopes. J Virol 75: 4195–4207.
Malhotra U, Holte S, Zhu T, Delpit E, Huntsberry C, et al. (2003) Early induction and maintenance of Env-specific T-helper cells following human immunodeficiency virus type 1 infection. J Virol 77: 2663–2674.