ISCOMATRIXTM Adjuvant Research Articles

The utility of ISCOMATRIX™ adjuvant for dose reduction of antigen for vaccines requiring antibody responses

The capacity of an adjuvant to reduce the amount of antigen required in vaccines would be beneficial in a variety of settings, including situations where antigen is difficult or expensive to manufacture, or in situations where demand exceeds production capacity, such as pandemic influenza. The ability to reduce antigen dose would also be a significant advantage in combination vaccines, and vaccines that by necessity must contain multiple antigens to accommodate variability between strains or genotypes. ISCOMATRIX™ adjuvant was compared to aluminium hydroxide adjuvant (Al(OH 3)) for induction of antibody responses and dose sparing of a recombinant HIV gp120 vaccine. Neutralising antibody responses were significantly greater, at the same protein dose, when the gp120 protein was formulated with ISCOMATRIX™ adjuvant compared to Al(OH 3). Moreover, strong responses were achieved with up to 100-fold lower doses of gp120 using ISCOMATRIX™ adjuvant. Therefore, ISCOMATRIX™ adjuvant has the potential to substantially reduce the dose of antigen required in human vaccines, without compromising the immune response.

Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX™ adjuvant in women with cervical intraepithelial neoplasia

Purpose : Persistent infection of cervical epithelium with “high risk” human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX™ adjuvant (HPV16 Immunotherapeutic) for patients with CIN. Experimental design : Patients with CIN ( n = 31) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. Results : Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. Conclusions : The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX™ adjuvant is safe and induces vaccine antigen specific cell mediated immunity.

Association of antigens to ISCOMATRIX™ adjuvant using metal chelation leads to improved CTL responses

The association of antigen with ISCOMATRIX™ adjuvant has been shown to be important for the optimal induction of cytotoxic T lymphocyte (CTL) responses. Here, we describe a simple broadly applicable method for associating recombinant proteins with hexa-histidine tags to ISCOMATRIX™ adjuvant utilising metal-affinity chelating interactions. The metal chelation binding step can be performed in a wide range of buffers, including commonly used denaturants such as urea, which makes it an ideal strategy for formulating proteins which are otherwise insoluble. Following association of protein with the chelating ISCOMATRIX™ adjuvant, the denaturant can be removed. Further, we show enhanced CTL responses with a protein-associated chelating ISCOMATRIX™ vaccine compared to a non-associated ISCOMATRIX™ vaccine.

ISCOMATRIX™ adjuvant: an adjuvant suitable for use in anticancer vaccines

Human Papillomavirus type 16 (HPV16) E6 and E7 oncoproteins are associated with cervical cancer development and progression and can therefore be used as target antigens for cancer immunotherapy. In this study we evaluated the immunogenicity in mice, of different vaccine formulations using recombinant HPV16 derived E6E7 or E7GST fusion proteins. When co-administered with ISCOMATRIX™ adjuvant, these E6E7 proteins consistently induced E7 specific CTL, in vivo tumor protection, antibody and DTH responses. ISCOMATRIX™ adjuvant has been developed for use in the formulation of novel human vaccines and has been evaluated for safety and toxicity in human trials. A formulation containing aluminum hydroxide (Al(OH) 3) gave a lesser degree of E7 specific antibody, and no local E7 specific CTL response but similar DTH and tumor protection. These findings demonstrate the potential of ISCOMATRIX™ adjuvant to stimulate both cellular and humoral immune responses to endogenously processed target antigens, and hence is the preferred adjuvant when CTL responses are desirable.

ISCOMATRIX TM adjuvant: a potent inducer of humoral and cellular immune responses

ISCOMATRIX TM adjuvant is capable of inducing broad and potent humoral and cellular immune responses. The components are well defined and the manufacturing process is simple and robust. Many vaccines containing the ISCOMATRIX TM adjuvant have been tested in a range of animal models, including human and non-human primates. Strong antibody and T cell responses have been induced in these studies [1]. The antibody response is often achieved with lesser amounts of antigen than other adjuvant systems and the maximal responses have also been reached more quickly. Both CD4 + and CD8 + T cell responses are induced with the cytotoxic T lymphocyte responses being very long lived. Additionally, ISCOMATRIX TM adjuvant can be used in vaccines for induction of mucosal immune responses. This review provides an overview of the immune responses that can be elicited using ISCOMATRIX TM vaccines and the current state of knowledge regarding the mechanism of action of this adjuvant.